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Sample records for analysis reveals arsenic-induced

  1. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-01-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered. PMID:27585557

  2. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  3. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Feussner, J.R.; Shelburne, J.D.; Bredehoeft, S.; Cohen, H.J.

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-proble analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  4. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis.

    Science.gov (United States)

    Feussner, J R; Shelburne, J D; Bredehoeft, S; Cohen, H J

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  5. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  6. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  7. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  8. Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Afzal Sheikh; Zahangir Alam Saud; Khaled Hossain; Fouzia Yeasmin; Smita Agarwal; Mashiur Rahman; Khairul Islam; Ekhtear Hossain; Shakhawoat Hossain; Md Rezaul Karim; Farjana Nikkon

    2014-01-01

    Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice.Methods:non-treated control group while, the second, third, and fourth groups were treated with M.oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice.Results:Swiss albino male mice were divided into four groups. The first group was used as induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol.Conclusions:The results indicate that the leaves of M. oleifera may be useful in reducing the It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-effects of arsenic-induced toxicity.

  9. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  10. Effects of Echinacea Purpurea on Wound Healing after Arsenic Induced Skin Necrosis

    Directory of Open Access Journals (Sweden)

    Annahita Rezaie

    2013-11-01

    Full Text Available Background: Evaluation of healing effects of Echinacea extract in Arsenic induced dermal necrosis in rat is the objective of this study. Materials and Methods: In this experimental study 20 male Wistar rats were divided to 2 groups. Dermal necrosis was induced by subcutaneously arsenic injection (4mg/kg for 10 days. In group 2, after arsenic receiving, Echinacea were injected intraperitoneally (400mg/kg. After last day of injection, rats were euthanizes and pathologic samples were collected from dermal ulcers.Results: Histopathologic results revealed necrosis of different dermal layers in arsenic group. There were inflammatory exudates instead of impaired structures. In group 2, there were granulation tissue with high cellularity and new vessels.Conclusion: According to this research findings arsenic can induce dermal necrosis which is a good animal model for dermatologic researches and also Echinacea has healing effects and can protect and limit the Arsenic effects.

  11. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N; Bibby, Kyle J; Stolz, Donna B; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L; Barchowsky, Aaron; Stolz, John F

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes.

  12. 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells.

    Science.gov (United States)

    Gong, Xuezhong; Ivanov, Vladimir N; Hei, Tom K

    2016-09-01

    Our recent study demonstrated that sodium arsenite at a clinically relevant dose induced nephrotoxicity in human renal proximal tubular epithelial cell line HK-2, which could be inhibited by natural product 2,3,5,6-tetramethylpyrazine (TMP) with antioxidant activity. The present study demonstrated that arsenic exposure resulted in protein and enzymatic induction of heme oxygenase-1 (HO-1) in dose- and time-dependent manners in HK-2 cells. Blocking HO-1 enzymatic activity by zinc protoporphyrin (ZnPP) augmented arsenic-induced apoptosis, ROS production and mitochondrial dysfunction, suggesting a critical role for HO-1 as a renal protectant in this procession. On the other hand, TMP, upstream of HO-1, inhibited arsenic-induced ROS production and ROS-dependent HO-1 expression. TMP also prevented mitochondria dysfunction and suppressed activation of the intrinsic apoptotic pathway in HK-2 cells. Our results revealed that the regulation of arsenic-induced HO-1 expression was performed through multiple ROS-dependent signal pathways and the corresponding transcription factors, including p38 MAPK and JNK (but not ERK), AP-1, Nrf2 and NF-κB. TMP inhibited arsenic-induced activations of JNK, p38 MAPK, ERK, AP-1 and Nrf2 and block HO-1 protein expression. The present study, furthermore, demonstrated arsenic-induced expression of arsenic response protein 2 (ARS2) that was regulated by p38 MAPK, ERK and NF-κB. To our knowledge, this is the first report showing that ARS2 involved in arsenic-induced nephrotoxicity, while TMP pretreatment prevented such an up-regulation of ARS2 in HK-2 cells. Given ARS2 and HO-1 sharing the similar regulation mechanism, we speculated that ARS2 might also mediate cell survival in this procession. In summary, our study highlighted a role of HO-1 in the protection against arsenic-induced cytotoxicity downstream from the primary targets of TMP and further indicated that TMP may be used as a potential therapeutic agent in the treatment of arsenic-induced

  13. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  14. Arsenic-induced morphogenic response in roots of arsenic hyperaccumulator fern Pteris vittata.

    Science.gov (United States)

    Forino, Laura Maria Costantina; Ruffini Castiglione, Monica; Bartoli, Giacomo; Balestri, Mirko; Andreucci, Andrea; Tagliasacchi, Anna Maria

    2012-10-15

    On the assumption that arsenic induces stress morphogenetic responses involved in As tolerance and hyperaccumulation in the Pteris vittata fern, we analyzed the root system of young sporophytes grown in 250, 334, and 500 μM As for five days and for 14 days. Anatomical and histological analyses were performed in plants grown for five days to evaluate the number, position, length and differentiation pattern of root hairs. AgNOR staining, employed to study nucleolus behavior in root apices, showed that arsenic influences nucleolar activity (evaluated by nucleolus size, number and absorbance) in the root meristem. In plants treated with 250 and 334 μM As an acropetal shift of root hair development and an increase in hair length and density were observed, linked to an ectopic pattern of differentiation. The opposite trend was recorded in plants treated with 500 μM As. It is worth noting the presence of living border-like cells, not yet observed in ferns, and their increase following As treatments. Analysis and vitality of border-like cells were surveyed after 14 days of treatments. In conclusion As treatments elicited a stress-induced morphogenic response which, by modifying the differentiation pattern, number and length of root hairs, modulating nucleolar activity and interacting with the rhizosphere by inducing border-like cell production, may adjust the rate of root uptake and its metabolic activity.

  15. Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells.

    Science.gov (United States)

    Pan, Xiao; Jiang, Liping; Zhong, Laifu; Geng, Chengyan; Jia, Li; Liu, Shuang; Guan, Huai; Yang, Guang; Yao, Xiaofeng; Piao, Fengyuan; Sun, Xiance

    2016-02-01

    Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

  16. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  17. Is Utility Transferable? A Revealed Preference Analysis

    NARCIS (Netherlands)

    Cherchye, L.J.H.; Demuynck, T.; de Rock, B.

    2011-01-01

    We provide a revealed preference analysis of the transferable utility hypothesis, which is widely used in economic models. First, we establish revealed preference conditions that must be satisfied for observed group behavior to be consistent with Pareto efficiency under transferable utility. Next, w

  18. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  19. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  20. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  1. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  2. Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment

    Institute of Scientific and Technical Information of China (English)

    Garima Sharma; Madhu Kumar

    2012-01-01

    Arsenic has a suppressive influence on spermatogenesis and induces impairment in male reproductive system due to oxidative stress.The present study was aimed to test the arsenic induced toxicity and protection by Chlorophytum borivilianum.The effect of sodium arsenite (4 mg/(kg body weight (bw)·day)) via double distilled water without or with C.borivilianum (800 mg/(kg bw·day)) was evaluated in Swiss albino mice for 30 days.The radical scavenging activity of the aqueous C.borivilianum root extract was measured using DPPH (l,l-diphenyl-2-picryl hydrayzyl) radical.Qualitative assessment of various cell types in the testis,sperm count and motility,testicular activity of lipid peroxidation (LPO),reduced glutathione (GSH),acid and alkaline phosphatase,cholesterol and serum testosterone were monitored.Arsenic treatment showed a significant increase in LPO,acid and alkaline phosphatase,cholesterol and decrease in sperm count,sperm motility,GSH and serum testosterone.Combined treatment showed significant decrease in LPO,acid and alkaline phosphatase,cholesterol and elevation in sperm count,sperm motility,GSH and serum testosterone.Testiculat histopathology showed that C.borivilianum had reduced degeneration of germ cell in the seminiferous tubules and loss of sperms induced by arsenic intoxication.The results thus led us to conclude that administration of C.borivilianum root extract is found to be protective against arsenic induced toxicity.

  3. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-07-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage. PMID:26524343

  4. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  5. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  6. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  7. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  8. Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.

    Science.gov (United States)

    Muthumani, M; Miltonprabu, S

    2015-06-25

    Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical β-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5 mg kg(-1) bw/day) with THC (80 mg kg(-1) bw/day) for 28 days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat.

  9. Selenium ameliorates arsenic induced oxidative stress through modulation of antioxidant enzymes and thiols in rice (Oryza sativa L.).

    Science.gov (United States)

    Kumar, Amit; Singh, Rana Pratap; Singh, Pradyumna Kumar; Awasthi, Surabhi; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Tripathi, Rudra Deo

    2014-09-01

    Arsenic (As) contamination of rice is a major problem for South-East Asia. In the present study, the effect of selenium (Se) on rice (Oryza sativa L.) plants exposed to As was studied in hydroponic culture. Arsenic accumulation, plant growth, thiolic ligands and antioxidative enzyme activities were assayed after single (As and Se) and simultaneous supplementations (As + Se). The results indicated that the presence of Se (25 µM) decreased As accumulation by threefold in roots and twofold in shoots as compared to single As (25 µM) exposed plants. Arsenic induced oxidative stress in roots and shoots was significantly ameliorated by Se supplementation. The observed positive response was found associated with the increased activities of ascorbate peroxidase (APX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6) and glutathione peroxidase (GPx; EC 1.11.1.9) and induced levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) in As + Se exposed plants as compared to single As treatment. Selenium supplementation modulated the thiol metabolism enzymes viz., γ-glutamylcysteine synthetase (γ-ECS; EC 6.3.2.2), glutathione-S-transferase (GST; EC 2.5.1.18) and phytochelatin synthase (PCS; EC 2.3.2.15). Gene expression analysis of several metalloid responsive genes (LOX, SOD and MATE) showed upregulation during As stress, however, significant downregulation during As + Se exposure as compared to single As treatment. Gene expressions of enzymes of antioxidant and GSH and PC biosynthetic systems, such as APX, CAT, GPx, γ-ECS and PCS were found to be significantly positively correlated with their enzyme activities. The findings suggested that Se supplementation could be an effective strategy to reduce As accumulation and toxicity in rice plants.

  10. Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex.

    Science.gov (United States)

    Paul, Somnath; Banerjee, Nilanjana; Chatterjee, Aditi; Sau, Tanmoy J; Das, Jayanta K; Mishra, Prafulla K; Chakrabarti, Partha; Bandyopadhyay, Arun; Giri, Ashok K

    2014-04-01

    Arsenic in drinking water is of critical concern in West Bengal, India, as it results in several physiological symptoms including dermatological lesions and cancers. Impairment of the DNA repair mechanism has been associated with arsenic-induced genetic damage as well as with several cancers. ERCC2 (Excision Repair Cross-Complementing rodent repair, complementation group 2), mediates DNA-repair by interacting with Cdk-activating kinase (CAK) complex, which helps in DNA proof-reading during transcription. Arsenic metabolism alters epigenetic regulation; we tried to elucidate the regulation of ERCC2 in arsenic-exposed humans. Water, urine, nails, hair and blood samples from one hundred and fifty seven exposed and eighty eight unexposed individuals were collected. Dose dependent validation was done in vitro using HepG2 and HEK-293. Arsenic content in the biological samples was higher in the exposed individuals compared with the content in unexposed individuals (p < 0.001). Bisulfite-modified methylation specific PCR showed a significant (p < 0.0001) hypomethylation of the ERCC2 promoter in the arsenic-exposed individuals. Densitometric analysis of immunoblots showed a nearly two-fold increase in expression of ERCC2 in exposed individuals, but there was an enhanced genotoxic insult as measured by micronuclei frequency. Immuno-precipitation and western blotting revealed an increased (p < 0.001) association of Cdk7 with ERCC2 in highly arsenic exposed individuals. The decrease in CAK activity was determined by observing the intensity of Ser(392) phosphorylation in p53, in vitro, which decreased with an increase in arsenic dose. Thus we infer that arsenic biotransformation leads to promoter hypomethylation of ERCC2, which in turn inhibits the normal functioning of the CAK-complex, thus affecting DNA-repair; this effect was highest among the arsenic exposed individuals with dermatological lesions. PMID:24473091

  11. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  12. Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats.

    Science.gov (United States)

    Jalaludeen, Abdulkadhar Mohamed; Ha, Woo Tae; Lee, Ran; Kim, Jin Hoi; Do, Jeong Tae; Park, Chankyu; Heo, Young Tae; Lee, Won Young; Song, Hyuk

    2016-01-09

    Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT) occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day) and selenium (3 mg/kg·bw/day) resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day) did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day) partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day) attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases.

  13. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  14. ARSENIC INDUCES SUSTAINED IMPAIRMENT OF SKELETAL MUSCLE AND MUSCLE PROGENITOR CELL ULTRASTRUCTURE AND BIOENERGETICS

    Science.gov (United States)

    Fabrisia, Ambrosio; Elke, Brown; Donna, Stolz; Ricardo, Ferrari; Bret, Goodpaster; Bridget, Deasy; Giovanna, Distefano; Alexandra, Roperti; Amin, Cheikhi; Yesica, Garciafigueroa; Aaron, Barchowsky

    2014-01-01

    Over 4 million individuals in the US, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10 µg/L to over 1 mg/L, with 100 µg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. When compared to non-exposed controls, mice exposed to drinking water containing 100µg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There was no difference in levels of inorganic arsenic or its mononomethyl- and dimethyl- metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, as compared to cells isolated from non-exposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant. PMID:24960579

  15. Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.

    Science.gov (United States)

    Das, T K; Mani, V; Kaur, H; Kewalramani, N; De, S; Hossain, A; Banerjee, D; Datta, B K

    2012-07-01

    The present study was designed to assess whether supplementation of different levels of vitamin E to long-term arsenic exposed goats affords protection against the oxidative stress caused by the metalloid. Twenty-four crossbred lactating goats were distributed randomly into four groups (control, T(1), T(2) and T(3)) of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively, was also supplemented additionally for the period of 12 months. Compared to control, significant (p 63 %), plasma total Ig (22 %) and total antioxidant activity (24 %) was observed in only arsenic treated groups and vitamin E supplementation in both doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %, 48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end of experiment was (p arsenic exposed groups (1.003 ± 0.01) and significant (p arsenic induced oxidative stress and activities of antioxidant enzymes in goats.

  16. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    Science.gov (United States)

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

  17. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  18. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  19. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  20. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  1. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  2. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  3. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  4. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats.

    Science.gov (United States)

    Gupta, Richa; Kannan, Gurusamy M; Sharma, Mamta; S Flora, Swaran J

    2005-11-01

    the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator. PMID:21783626

  5. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  6. Activation of NADPH-recycling systems in leaves and roots of Arabidopsis thaliana under arsenic-induced stress conditions is accelerated by knock-out of Nudix hydrolase 19 (AtNUDX19) gene.

    Science.gov (United States)

    Corpas, Francisco J; Aguayo-Trinidad, Simeón; Ogawa, Takahisa; Yoshimura, Kazuya; Shigeoka, Shigeru

    2016-03-15

    NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions. Two major features were observed in the behavior of the main NADPH-recycling systems: (i) under optimal conditions in both organs, the levels of these activities were higher in nudx19 mutants than in Wt plants; and, (ii) under 500μM AsV conditions, these activities increase, especially in nudx19 mutant plants. Moreover, G6PDH activity in roots was the most affected enzyme in both Wt and nudx19 mutant plants, with a 4.6-fold and 5.0-fold increase, respectively. In summary, the data reveals a connection between the absence of chloroplastic AtNUDX19 and the rise in all NADP-dehydrogenase activities under physiological and arsenic-induced stress conditions, particularly in roots. This suggests that AtNUDX19 could be a key factor in modulating the NADPH pool in plants and consequently in redox homeostasis. PMID:26878367

  7. Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

    Science.gov (United States)

    Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

  8. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad, E-mail: mathar@uab.edu

    2013-09-06

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.

  9. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    OpenAIRE

    Kile, Molly L.; Faraj, Joycelyn M.; Ronnenberg, Alayne G.; Quamruzzaman, Quazi; Rahman, Mahmudar; Mostofa, Golam; Afroz, Sakila; Christiani, David C.

    2016-01-01

    Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association betwee...

  10. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

    Science.gov (United States)

    Wang, Lei; Hitron, John Andrew; Wise, James T F; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

  11. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  12. Molecular basis for arsenic-induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction.

    Science.gov (United States)

    Kumagai, Yoshito; Pi, Jingbo

    2004-08-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed.

  13. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats.

    Science.gov (United States)

    Bhadauria, S; Flora, S J S

    2007-03-01

    -exposed rats compared to that of normal animals. These changes were accompanied by a significant elevation in blood and soft-tissue arsenic concentration. Co-administration of DMSA and MiADMSA at lower dose (0.15 mmol/kg) was most effective not only in reducing arsenic-induced oxidative stress but also in depleting arsenic from blood and soft tissues compared to other treatments. This combination was also able to repair DNA damage caused following arsenic exposure. We thus recommend combined administration of DMSA and MiADMSA for achieving optimum effects of chelation therapy.

  14. Linear stability analysis reveals exclusion zone for sliding bed transport

    Directory of Open Access Journals (Sweden)

    Talmon Arnold M.

    2015-06-01

    Full Text Available A bend or any another pipe component disturbs solids transport in pipes. Longitudinal pressure profiles downstream of such a component may show a stationary transient harmonic wave, as revealed by a recent settling slurry laboratory experiment. Therefore the fundamental transient response of the two-layer model for fully stratified flow is investigated as a first approach. A linear stability analysis of the sliding bed configuration is conducted. No stationary transient harmonic waves are found in this analysis, but adaptation lengths for exponential recovery are quantified. An example calculation is given for a 0.1 m diameter pipeline.

  15. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  16. Systematic toxicological analysis revealing a rare case of captan ingestion.

    Science.gov (United States)

    Gottzein, Anne K; Musshoff, Frank; Madea, Burkhard

    2013-07-01

    This article presents a case of suicide by intoxication with various pharmaceuticals, particularly anticonvulsants, combined with the fungicide captan. A cause of death could not be ascertained at autopsy. However, systematic toxicological analysis (STA) including a screening via solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) for (semi) volatile organic compounds revealed results suggesting a possible cause of death. The effects of captan on the human organism, its metabolism, and distribution will be discussed. Macroscopically, the cause of death was unascertained. STA revealed clonazepam, citalopram, and its metabolites, lamotrigine, levetiracetam, lacosamide, clonazepam, captan, and its metabolite tetrahydrophthalimide (THPI). For the first time, it was detected in human viscera. A quantification of THPI was performed to obtain distribution in the organs. The significance of a complete STA must be emphasized. The presence of THPI would have been missed without previous detection of captan. Consequently, this fatality would not have been investigated satisfactorily.

  17. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  18. Arsenic-induced intensity oscillations in reflection high-energy electron diffraction measurements. [during MBE of GaAs and InAs

    Science.gov (United States)

    Lewis, B. F.; Fernandez, R.; Grunthaner, F. J.; Madhukar, A.

    1986-01-01

    A technique of arsenic-induced RHEED intensity oscillations has been used to accurately measure arsenic incorporation rates as a function of substrate temperature during the homoepitaxial growths of both GaAs and InAs by molecular beam epitaxy (MBE). Measurements were made at growth temperatures from 350 to 650 C and at arsenic fluxes of 0.1 to 10.0 monolayer/s. The method measures only the arsenic actually incorporated into the growing film and does not include the arsenic lost in splitting the arsenic tetramers or lost by evaporation from the sample.

  19. Nitric oxide alleviates arsenic-induced toxic effects in ridged Luffa seedlings.

    Science.gov (United States)

    Singh, Vijay Pratap; Srivastava, Prabhat Kumar; Prasad, Sheo Mohan

    2013-10-01

    Hydroponic experiments were conducted to investigate whether exogenous addition of nitric oxide (NO) as sodium nitroprusside (SNP) alleviates arsenic (As) toxicity in Luffa acutangula (L.) Roxb. seedlings. Arsenic (5 and 50 μM) declined growth of Luffa seedlings which was accompanied by significant accumulation of As. SNP (100 μM) protected Luffa seedlings against As toxicity as it declined As accumulation significantly. The photosynthetic pigments and chlorophyll fluorescence parameters such as Fv/Fm, Fv/F0, Fm/F0 and qP were decreased while NPQ was raised by As. However, the toxic effects of As on photosynthesis were significantly ameliorated by SNP. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As, however, these oxidative indices were diminished significantly in the presence of SNP. As treatment stimulated the activities of SOD and CAT while the activities of APX and GST, and AsA content and AsA/DHA ratio were decreased. Upon SNP addition, along with further rise in SOD and CAT activity, APX and GST activity, and levels of AsA and AsA/DHA ratio were restored considerably. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, APX and GST activities and decreased AsA content, hence led to the oxidative stress. However, the addition of SNP protected seedlings against As stress by regulating As accumulation, oxidative stress and antioxidant defense system.

  20. Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

    Science.gov (United States)

    Shukla, Pratiksha; Singh, A K

    2015-09-01

    The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

  1. Geometric morphometric analysis reveals sexual dimorphism in the distal femur.

    Science.gov (United States)

    Cavaignac, Etienne; Savall, Frederic; Faruch, Marie; Reina, Nicolas; Chiron, Philippe; Telmon, Norbert

    2016-02-01

    An individual's sex can be determined by the shape of their distal femur. The goal of this study was to show that differences in distal femur shape related to sexual dimorphism could be identified, visualized, and quantified using 3D geometric morphometric analysis. Geometric morphometric analysis was carried out on CT scans of the distal femur of 256 subjects living in the south of France. Ten landmarks were defined on 3D reconstructions of the distal femur. Both traditional metric and geometric morphometric analyses were carried out on these bone reconstructions; these analyses identified trends in bone shape in sex-based subgroups. Sex-related differences in shape were statistically significant. The subject's sex was correctly assigned in 77.3% of cases using geometric morphometric analysis. This study has shown that geometric morphometric analysis of the distal femur is feasible and has revealed sexual dimorphism differences in this bone segment. This reliable, accurate method could be used for virtual autopsy and be used to perform diachronic and interethnic comparisons. Moreover, this study provides updated morphometric data for a modern population in the south of France. PMID:26743712

  2. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  3. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  4. Single cell transcriptional analysis reveals novel innate immune cell types

    Directory of Open Access Journals (Sweden)

    Linda E. Kippner

    2014-06-01

    Full Text Available Single-cell analysis has the potential to provide us with a host of new knowledge about biological systems, but it comes with the challenge of correctly interpreting the biological information. While emerging techniques have made it possible to measure inter-cellular variability at the transcriptome level, no consensus yet exists on the most appropriate method of data analysis of such single cell data. Methods for analysis of transcriptional data at the population level are well established but are not well suited to single cell analysis due to their dependence on population averages. In order to address this question, we have systematically tested combinations of methods for primary data analysis on single cell transcription data generated from two types of primary immune cells, neutrophils and T lymphocytes. Cells were obtained from healthy individuals, and single cell transcript expression data was obtained by a combination of single cell sorting and nanoscale quantitative real time PCR (qRT-PCR for markers of cell type, intracellular signaling, and immune functionality. Gene expression analysis was focused on hierarchical clustering to determine the existence of cellular subgroups within the populations. Nine combinations of criteria for data exclusion and normalization were tested and evaluated. Bimodality in gene expression indicated the presence of cellular subgroups which were also revealed by data clustering. We observed evidence for two clearly defined cellular subtypes in the neutrophil populations and at least two in the T lymphocyte populations. When normalizing the data by different methods, we observed varying outcomes with corresponding interpretations of the biological characteristics of the cell populations. Normalization of the data by linear standardization taking into account technical effects such as plate effects, resulted in interpretations that most closely matched biological expectations. Single cell transcription

  5. Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia.

    Directory of Open Access Journals (Sweden)

    Luca Fagnocchi

    Full Text Available Most bacterial small RNAs (sRNAs are post-transcriptional regulators involved in adaptive responses, controlling gene expression by modulating translation or stability of their target mRNAs often in concert with the RNA chaperone Hfq. Neisseria meningitides, the leading cause of bacterial meningitis, is able to adapt to different host niches during human infection. However, only a few sRNAs and their functions have been fully described to date. Recently, transcriptional expression profiling of N. meningitides in human blood ex vivo revealed 91 differentially expressed putative sRNAs. Here we expanded this analysis by performing a global transcriptome study after exposure of N. meningitides to physiologically relevant stress signals (e.g. heat shock, oxidative stress, iron and carbon source limitation. and we identified putative sRNAs that were differentially expressed in vitro. A set of 98 putative sRNAs was obtained by analyzing transcriptome data and 8 new sRNAs were validated, both by Northern blot and by primer extension techniques. Deletion of selected sRNAs caused attenuation of N. meningitides infection in the in vivo infant rat model, leading to the identification of the first sRNAs influencing meningococcal bacteremia. Further analysis indicated that one of the sRNAs affecting bacteremia responded to carbon source availability through repression by a GntR-like transcriptional regulator. Both the sRNA and the GntR-like regulator are implicated in the control of gene expression from a common network involved in energy metabolism.

  6. Isotope analysis reveals foraging area dichotomy for atlantic leatherback turtles.

    Directory of Open Access Journals (Sweden)

    Stéphane Caut

    Full Text Available BACKGROUND: The leatherback turtle (Dermochelys coriacea has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI. Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. METHODOLOGY/PRINCIPAL FINDINGS: Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal and foraging latitude (North Atlantic vs. West African coasts, respectively. Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. CONCLUSIONS/SIGNIFICANCE: Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by

  7. Quantitative flux analysis reveals folate-dependent NADPH production

    Science.gov (United States)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  8. Power analysis attacks revealing the secrets of smart cards

    CERN Document Server

    Mangard, Stefan; Popp, Thomas

    2008-01-01

    A comprehensive treatment of power analysis attacks and countermeasures. Based on the principle that the only way to defend against power analysis attacks is to understand them, this book explains how power analysis attacks work. It discusses simple and differential power analysis as well as advanced techniques like template attacks.

  9. BAHAMAS: new SNIa analysis reveals inconsistencies with standard cosmology

    CERN Document Server

    Shariff, H; Trotta, R; van Dyk, D A

    2015-01-01

    We present results obtained by applying our BAyesian HierArchical Modeling for the Analysis of Supernova cosmology (BAHAMAS) software package to the 740 spectroscopically confirmed supernovae type Ia (SNIa) from the "Joint Light-curve Analysis" (JLA) dataset. We simultaneously determine cosmological parameters and standardization parameters, including host galaxy mass corrections, residual scatter and object-by-object intrinsic magnitudes. Combining JLA and Planck Cosmic Microwave Background data, we find significant discrepancies in cosmological parameter constraints with respect to the standard analysis: we find Omega_M = 0.399+/-0.027, 2.8\\sigma\\ higher than previously reported and w = -0.910+/-0.045, 1.6\\sigma\\ higher than the standard analysis. We determine the residual scatter to be sigma_res = 0.104+/-0.005. We confirm (at the 95% probability level) the existence of two sub-populations segregated by host galaxy mass, separated at log_{10}(M/M_solar) = 10, differing in mean intrinsic magnitude by 0.055+...

  10. Arsenic Induced Inhibition of δ-aminolevulinate Dehydratase Activity in Rat Blood and its Response To Meso 2,3-dimercaptosuccinic Acid and Monoisoamyl DMSA

    Institute of Scientific and Technical Information of China (English)

    SMRATI BHADAURIA; SWARAN J.S.FLORA

    2004-01-01

    Objective The objective of this study was to investigate arsenic induced changes in blood δ-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (Ⅲ) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (Ⅲ and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (Ⅲ) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (Ⅲ), but at two higher concentrations (0.5and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood

  11. Penicillium simile sp. nov. revealed by morphological and phylogenetic analysis.

    Science.gov (United States)

    Davolos, Domenico; Pietrangeli, Biancamaria; Persiani, Anna Maria; Maggi, Oriana

    2012-02-01

    The morphology of three phenetically identical Penicillium isolates, collected from the bioaerosol in a restoration laboratory in Italy, displayed macro- and microscopic characteristics that were similar though not completely ascribable to Penicillium raistrickii. For this reason, a phylogenetic approach based on DNA sequencing analysis was performed to establish both the taxonomic status and the evolutionary relationships of these three peculiar isolates in relation to previously described species of the genus Penicillium. We used four nuclear loci (both rRNA and protein coding genes) that have previously proved useful for the molecular investigation of taxa belonging to the genus Penicillium at various evolutionary levels. The internal transcribed spacer region (ITS1-5.8S-ITS2), domains D1 and D2 of the 28S rDNA, a region of the tubulin beta chain gene (benA) and part of the calmodulin gene (cmd) were amplified by PCR and sequenced. Analysis of the rRNA genes and of the benA and cmd sequence data indicates the presence of three isogenic isolates belonging to a genetically distinct species of the genus Penicillium, here described and named Penicillium simile sp. nov. (ATCC MYA-4591(T)  = CBS 129191(T)). This novel species is phylogenetically different from P. raistrickii and other related species of the genus Penicillium (e.g. Penicillium scabrosum), from which it can be distinguished on the basis of morphological trait analysis.

  12. Subfield profitability analysis reveals an economic case for cropland diversification

    Science.gov (United States)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  13. Leukemia surfaceome analysis reveals new disease-associated features.

    Science.gov (United States)

    Mirkowska, Paulina; Hofmann, Andreas; Sedek, Lukasz; Slamova, Lucie; Mejstrikova, Ester; Szczepanski, Tomasz; Schmitz, Maike; Cario, Gunnar; Stanulla, Martin; Schrappe, Martin; van der Velden, Vincent H J; Bornhauser, Beat C; Wollscheid, Bernd; Bourquin, Jean-Pierre

    2013-06-20

    A better description of the leukemia cell surface proteome (surfaceome) is a prerequisite for the development of diagnostic and therapeutic tools. Insights into the complexity of the surfaceome have been limited by the lack of suitable methodologies. We combined a leukemia xenograft model with the discovery-driven chemoproteomic Cell Surface Capture technology to explore the B-cell precursor acute lymphoblastic leukemia (BCP-ALL) surfaceome; 713 cell surface proteins, including 181 CD proteins, were detected through combined analysis of 19 BCP-ALL cases. Diagnostic immunophenotypes were recapitulated in each case, and subtype specific markers were detected. To identify new leukemia-associated markers, we filtered the surfaceome data set against gene expression information from sorted, normal hematopoietic cells. Nine candidate markers (CD18, CD63, CD31, CD97, CD102, CD157, CD217, CD305, and CD317) were validated by flow cytometry in patient samples at diagnosis and during chemotherapy. CD97, CD157, CD63, and CD305 accounted for the most informative differences between normal and malignant cells. The ALL surfaceome constitutes a valuable resource to assist the functional exploration of surface markers in normal and malignant lymphopoiesis. This unbiased approach will also contribute to the development of strategies that rely on complex information for multidimensional flow cytometry data analysis to improve its diagnostic applications. PMID:23649467

  14. Changes in cod muscle proteins during frozen storage revealed by proteome analysis and multivariate data analysis

    DEFF Research Database (Denmark)

    Kjærsgård, Inger Vibeke Holst; Nørrelykke, M.R.; Jessen, Flemming

    2006-01-01

    Multivariate data analysis has been combined with proteomics to enhance the recovery of information from 2-DE of cod muscle proteins during different storage conditions. Proteins were extracted according to 11 different storage conditions and samples were resolved by 2-DE. Data generated by 2-DE...... was subjected to principal component analysis (PCA) and discriminant partial least squares regression (DPLSR). Applying PCA to 2-DE data revealed the samples to form groups according to frozen storage time, whereas differences due to different storage temperatures or chilled storage in modified atmosphere...... light chain 1, 2 and 3, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, aldolase A and two ?-actin fragments, and a nuclease diphosphate kinase B fragment to change in concentration, during frozen storage. Application of proteomics, multivariate data analysis and MS/MS to analyse...

  15. Modes of embayed beach dynamics: analysis reveals emergent timescales

    Science.gov (United States)

    Murray, K. T.; Murray, A.; Limber, P. W.; Ells, K. D.

    2013-12-01

    Embayed beaches, or beaches positioned between rocky headlands, exhibit morphologic changes over many length and time scales. Beach sediment is transported as a result of the day-to-day wave forcing, causing patterns of erosion and accretion. We use the Rocky Coastline Evolution Model (RCEM) to investigate how patterns of shoreline change depend on wave climate (the distribution of wave-approach angles) and beach characteristics. Measuring changes in beach width through time allows us to track the evolution of the shape of the beach and the movement of sand within it. By using Principle Component Analysis (PCA), these changes can be categorized into modes, where the first few modes explain the majority of the variation in the time series. We analyze these modes and how they vary as a function of wave climate and headland/bay aspect ratio. In the purposefully simple RCEM, sediment transport is wave-driven and affected by wave shadowing behind the headlands. The rock elements in our model experiments (including the headlands) are fixed and unerodable so that this analysis can focus purely on sand dynamics between the headlands, without a sand contribution from the headlands or cliffs behind the beach. The wave climate is characterized by dictating the percentage of offshore waves arriving from the left and the percentage of waves arriving from high angles (very oblique to the coastline orientation). A high-angle dominated wave climate tends to amplify coastline perturbations, whereas a lower-angle wave climate is diffusive. By changing the headland/bay aspect ratio and wave climate, we can perform PCA analysis of generalized embayed beaches with differing anatomy and wave climate forcings. Previous work using PCA analysis of embayed beaches focused on specific locations and shorter timescales (beach dynamics over longer timescales. The first two PCA modes, which explain a majority of the beach width time series variation (typically >70%), are a 'breathing' mode and a

  16. Genome analysis of the platypus reveals unique signatures of evolution

    Science.gov (United States)

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  17. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  18. Research Progress on Molecular Mechanisms of Arsenic- induced Oxidative Stress%砷的氧化应激分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    白彩军; 刘丹; 李冰

    2012-01-01

    砷暴露能够引起多种疾病和病理损伤.目前氧化应激机制是砷毒性的研究热点.砷通过扰乱氧化/抗氧化平衡,从而引起细胞信号通路和转录因子活性、细胞周期和细胞凋亡、线粒体、抗氧化物酶的活性、抗氧化防御系统等方面的改变.本文将就砷的氧化应激分子机制的研究进展进行综述.%Arsenic exposure can cause a variety of diseases and pathological damages. In recent years, oxidative stress mechanism has been considered to be the research focus of arsenic toxicity. Arsenic alters multiple cellular pathways and transcription factor activities, cell cycle and cell apoptosis, mitochondria, antioxidant enzymes activity, and antioxidant defense system by disturbing the pro/antioxidant balance. This review summarizes the molecular mechanism of arsenic- induced oxidative stress.

  19. Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity.

    Science.gov (United States)

    Papanikolaou, G; Politou, M; Terpos, E; Fourlemadis, S; Sakellaropoulos, N; Loukopoulos, D

    2000-04-01

    Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%. Identification of a candidate HFE gene in 1996 was soon followed by the description of two ancestral mutations, i.e., c.845G-->A (C282Y) and c.187C-->G (H63D). To these was recently added the mutation S65C, which may represent a simple polymorphism. The incidence of HH in Greece is unknown but clinical cases are rare. Also unknown is the carrier frequency of the two mutant alleles. A first estimate of the latter is given in the present report. It is based on data from the genetic analysis of 10 unrelated patients of Greek origin who were referred to our center for genotyping and 158 unselected male blood donors. The allele frequencies for the C282Y and H63D mutations were 0.003 and 0.145, respectively. The C282Y allele was detected in 50% of HH patients. This is considerably lower than the frequencies reported for HH patients in the U.S.A. (82%) and France (91 %) and closer to that reported in Italy (64%). Five patients did not carry any known HFE mutation; three may represent cases of juvenile hemochromatosis, given their early onset with iron overload, hypogonadism, and heart disease. We suggest that genetic heterogeneity is more prominent in Southern Europe. It is also possible that the penetrance of the responsible genes is different across the Mediterranean.

  20. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners

    Science.gov (United States)

    Golemiec, Mireille; Schneider, Jonathan; Boyce, W. Thomas; Bush, Nicole R.; Adler, Nancy; Levine, Joel D.

    2016-01-01

    The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioral interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of “reciprocal” interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored. PMID:26973572

  1. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    David P Hall

    Full Text Available Acute mountain sickness (AMS is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS, we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25. These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  2. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners.

    Science.gov (United States)

    Golemiec, Mireille; Schneider, Jonathan; Boyce, W Thomas; Bush, Nicole R; Adler, Nancy; Levine, Joel D

    2016-01-01

    The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioral interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of "reciprocal" interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored. PMID:26973572

  3. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners

    Directory of Open Access Journals (Sweden)

    Mireille eGolemiec

    2016-03-01

    Full Text Available The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioural interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of ‘reciprocal’ interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored.

  4. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  5. Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity.

    Science.gov (United States)

    Munro, Kristie L; Mariana, Anna; Klavins, Andrejs I; Foster, Amalanie J; Lai, Barry; Vogt, Stefan; Cai, ZhongHou; Harris, Hugh H; Dillon, Carolyn T

    2008-09-01

    Arsenic (As) is responsible for mass-poisonings worldwide following the ingestion of As-contaminated drinking water. Importantly, however, As toxicity is exploited in the antileukemia drug, Trisenox (As2O3), which successfully cures 65-80% of patients suffering relapsed acute promyelocytic leukemia. In an effort to determine the intracellular organelle and biomolecular targets of As, microprobe X-ray fluorescence (XRF) and X-ray absorption spectroscopy (XAS) analyses were performed on HepG2 cells following their exposure to high doses of arsenite (1 mM) or arsenate (20 mM). Microprobe XRF elemental mapping of thin-sectioned cells showed As accumulation in the euchromatin region of the cell nucleus (following arsenite exposure) synonymous with As targeting of DNA or proteins involved in DNA transcription. X-ray absorption near edge spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS) analysis of arsenite-treated cells, however, showed the predominance of an As tris-sulfur species, providing increased credence to As interactions with nuclear proteins as a key factor in As-induced toxicity. PMID:18597498

  6. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Institute of Scientific and Technical Information of China (English)

    Yonglong Yu; Dong Zhu; Chaoying Ma; Hui Cao; Yaping Wang; Yanhao Xu; Wenying Zhang; Yueming Yan

    2016-01-01

    Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20) during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA) was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further informa-tion about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  7. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  8. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

    OpenAIRE

    Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the exis...

  9. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas

    DEFF Research Database (Denmark)

    Cirilo, Priscila Daniele Ramos; Marchi, Fábio Albuquerque; Barros Filho, Mateus de Camargo;

    2013-01-01

    integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell...... transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs....

  10. Analysis of self-overlap reveals trade-offs in plankton swimming trajectories

    DEFF Research Database (Denmark)

    Mariani, Patrizio; Visser, Andre W.; Mazzocchi, Maria Grazia;

    2014-01-01

    these contrasting processes. This trade-off can be hypothesized as being evident in the behaviour of plankton, which inhabit a dilute three-dimensional environment with few refuges or orienting landmarks. We present an analysis of the swimming path geometries based on a volumetric Monte Carlo sampling approach......, which is particularly adept at revealing such trade-offs by measuring the self-overlap of the trajectories. Application of this method to experimentally measured trajectories reveals that swimming patterns in copepods are shaped to efficiently explore volumes at small scales, while achieving a large...

  11. Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation.

    Science.gov (United States)

    Malakar, Arup Kumar; Halder, Binata; Paul, Prosenjit; Chakraborty, Supriyo

    2016-09-15

    Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD. PMID:27275533

  12. Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis

    OpenAIRE

    Lin, Yuan-Pin; Duann, Jeng-Ren; Feng, Wenfeng; Chen, Jyh-Horng; Jung, Tzyy-Ping

    2014-01-01

    Background Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. Method This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Results Empirical results showed that music with major mode ...

  13. Reticulate evolutionary history and extensive introgression in mosquito species revealed by phylogenetic network analysis.

    Science.gov (United States)

    Wen, Dingqiao; Yu, Yun; Hahn, Matthew W; Nakhleh, Luay

    2016-06-01

    The role of hybridization and subsequent introgression has been demonstrated in an increasing number of species. Recently, Fontaine et al. (Science, 347, 2015, 1258524) conducted a phylogenomic analysis of six members of the Anopheles gambiae species complex. Their analysis revealed a reticulate evolutionary history and pointed to extensive introgression on all four autosomal arms. The study further highlighted the complex evolutionary signals that the co-occurrence of incomplete lineage sorting (ILS) and introgression can give rise to in phylogenomic analyses. While tree-based methodologies were used in the study, phylogenetic networks provide a more natural model to capture reticulate evolutionary histories. In this work, we reanalyse the Anopheles data using a recently devised framework that combines the multispecies coalescent with phylogenetic networks. This framework allows us to capture ILS and introgression simultaneously, and forms the basis for statistical methods for inferring reticulate evolutionary histories. The new analysis reveals a phylogenetic network with multiple hybridization events, some of which differ from those reported in the original study. To elucidate the extent and patterns of introgression across the genome, we devise a new method that quantifies the use of reticulation branches in the phylogenetic network by each genomic region. Applying the method to the mosquito data set reveals the evolutionary history of all the chromosomes. This study highlights the utility of 'network thinking' and the new insights it can uncover, in particular in phylogenomic analyses of large data sets with extensive gene tree incongruence. PMID:26808290

  14. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Directory of Open Access Journals (Sweden)

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  15. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  16. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    Directory of Open Access Journals (Sweden)

    Lingling Zhang

    Full Text Available Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  17. Local coexistence of VO2 phases revealed by deep data analysis

    Science.gov (United States)

    Strelcov, Evgheni; Ievlev, Anton; Belianinov, Alex; Tselev, Alexander; Kolmakov, Andrei; Kalinin, Sergei V.

    2016-07-01

    We report a synergistic approach of micro-Raman spectroscopic mapping and deep data analysis to study the distribution of crystallographic phases and ferroelastic domains in a defected Al-doped VO2 microcrystal. Bayesian linear unmixing revealed an uneven distribution of the T phase, which is stabilized by the surface defects and uneven local doping that went undetectable by other classical analysis techniques such as PCA and SIMPLISMA. This work demonstrates the impact of information recovery via statistical analysis and full mapping in spectroscopic studies of vanadium dioxide systems, which is commonly substituted by averaging or single point-probing approaches, both of which suffer from information misinterpretation due to low resolving power.

  18. The Revealed Competitiveness of Major Ports in the East Asian Region: An Additive Market Share Analysis

    Directory of Open Access Journals (Sweden)

    Tae Seung Kim

    2015-12-01

    Full Text Available In the single cargo market, the ordinary market share analysis method has been the representative tool for revealed competitiveness analysis. This paper develops and employs an applied market share index called the additive market share (AMS. Data are collected from 15 major container ports for the 1998-2013 period. In comparison to the results of an ordinary market share analysis, the highest AMS is observed for the Bohai Rim port cluster from 2008, not for the Yangtze River cluster or the Pearl River cluster. There are substitutable relationships between Yangtze River and non-Chinese ports and between Pearl River and Bohai Rim ports from 2001. Finally, there is an internal competition at Pearl River and Yangtze River ports, whereas Bohai Rim and non-Chinese ports show internally complementary relationships.

  19. A versatile multivariate image analysis pipeline reveals features of Xenopus extract spindles.

    Science.gov (United States)

    Grenfell, Andrew W; Strzelecka, Magdalena; Crowder, Marina E; Helmke, Kara J; Schlaitz, Anne-Lore; Heald, Rebecca

    2016-04-11

    Imaging datasets are rich in quantitative information. However, few cell biologists possess the tools necessary to analyze them. Here, we present a large dataset ofXenopusextract spindle images together with an analysis pipeline designed to assess spindle morphology across a range of experimental conditions. Our analysis of different spindle types illustrates how kinetochore microtubules amplify spindle microtubule density. Extract mixing experiments reveal that some spindle features titrate, while others undergo switch-like transitions, and multivariate analysis shows the pleiotropic morphological effects of modulating the levels of TPX2, a key spindle assembly factor. We also apply our pipeline to analyze nuclear morphology in human cell culture, showing the general utility of the segmentation approach. Our analyses provide new insight into the diversity of spindle types and suggest areas for future study. The approaches outlined can be applied by other researchers studying spindle morphology and adapted with minimal modification to other experimental systems. PMID:27044897

  20. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity

    Directory of Open Access Journals (Sweden)

    Eleanor Watson

    2014-09-01

    Full Text Available Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC–ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith–Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  1. Multilocus sequence analysis of nectar pseudomonads reveals high genetic diversity and contrasting recombination patterns.

    Directory of Open Access Journals (Sweden)

    Sergio Alvarez-Pérez

    Full Text Available The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA of four core housekeeping genes (rrs, gyrB, rpoB and rpoD. A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1; P. fluorescens, P. lutea and P. syringae (NG 2; and P. rhizosphaerae (NG 3. Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.

  2. Phylogenomic Analysis Reveals Extensive Phylogenetic Mosaicism in the Human GPCR Superfamily

    Directory of Open Access Journals (Sweden)

    Mathew Woodwark

    2007-01-01

    Full Text Available A novel high throughput phylogenomic analysis (HTP was applied to the rhodopsin G-protein coupled receptor (GPCR family. Instances of phylogenetic mosaicism between receptors were found to be frequent, often as instances of correlated mosaicism and repeated mosaicism. A null data set was constructed with the same phylogenetic topology as the rhodopsin GPCRs. Comparison of the two data sets revealed that mosaicism was found in GPCRs in a higher frequency than would be expected by homoplasy or the effects of topology alone. Various evolutionary models of differential conservation, recombination and homoplasy are explored which could result in the patterns observed in this analysis. We find that the results are most consistent with frequent recombination events. A complex evolutionary history is illustrated in which it is likely frequent recombination has endowed GPCRs with new functions. The pattern of mosaicism is shown to be informative for functional prediction for orphan receptors. HTP analysis is complementary to conventional phylogenomic analyses revealing mosaicism that would not otherwise have been detectable through conventional phylogenetics.

  3. VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

    Directory of Open Access Journals (Sweden)

    Ayling Roger D

    2008-11-01

    Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

  4. Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses.

    Science.gov (United States)

    Choudhury, Sreetama; Gupta, Payal; Ghosh, Sayan; Mukherjee, Sudeshna; Chakraborty, Priyanka; Chatterji, Urmi; Chattopadhyay, Sreya

    2016-05-16

    Arsenic contamination of drinking water is a matter of global concern. Arsenic intake impairs immune responses and leads to a variety of pathological conditions including cancer. In order to understand the intricate tuning of immune responses elicited by chronic exposure to arsenic, a mouse model was established by subjecting mice to different environmentally relevant concentrations of arsenic in drinking water for 30days. Detailed study of the thymus, a primary immune organ, revealed arsenic-mediated tissue damage in both histological specimens and scanning electron micrographs. Analysis of molecular markers of apoptosis by Western blot revealed a dose-dependent activation of the apoptotic cascade. Enzymatic assays supported oxidative stress as an instigator of cell death. Interestingly, assessment of inflammatory responses revealed disparity in the NF-κB/IL-6/STAT3 axis, where it was found that in animals consuming higher amounts of arsenic NF-κB activation did not lead to the classical IL-6 upregulation response. This deviation from the canonical pathway was accompanied with a significant rise in numbers of CD4+ CD25+ FoxP3 expressing cells in the thymus. The cytokine profile of the animals exposed to higher doses of arsenic also indicated an immune-suppressed milieu, thus validating that arsenic shapes the immune environment in context to its dose of exposure and that at higher doses it leads to immune-suppression. Our study establishes a novel role of arsenic in regulating immune homeostasis in context to its dose, where, at higher doses, arsenic related upregulation of NF-κB cascade takes on an alternative role that is correlated with increased immune-suppression.

  5. Single-cell analysis reveals a novel uncultivated magnetotactic bacterium within the candidate division OP3.

    Science.gov (United States)

    Kolinko, Sebastian; Jogler, Christian; Katzmann, Emanuel; Wanner, Gerhard; Peplies, Jörg; Schüler, Dirk

    2012-07-01

    Magnetotactic bacteria (MTB) are a diverse group of prokaryotes that orient along magnetic fields using membrane-coated magnetic nanocrystals of magnetite (Fe(3) O(4) ) or greigite (Fe(3) S(4) ), the magnetosomes. Previous phylogenetic analysis of MTB has been limited to few cultivated species and most abundant members of natural populations, which were assigned to Proteobacteria and the Nitrospirae phyla. Here, we describe a single cell-based approach that allowed the targeted phylogenetic and ultrastructural analysis of the magnetotactic bacterium SKK-01, which was low abundant in sediments of Lake Chiemsee. Morphologically conspicuous single cells of SKK-01 were micromanipulated from magnetically collected multi-species MTB populations, which was followed by whole genome amplification and ultrastructural analysis of sorted cells. Besides intracellular sulphur inclusions, the large ovoid cells of SKK-01 harbour ∼175 bullet-shaped magnetosomes arranged in multiple chains that consist of magnetite as revealed by TEM and EDX analysis. Sequence analysis of 16 and 23S rRNA genes from amplified genomic DNA as well as fluorescence in situ hybridization assigned SKK-01 to the candidate division OP3, which so far lacks any cultivated representatives. SKK-01 represents the first morphotype that can be assigned to the OP3 group as well as the first magnetotactic member of the PVC superphylum. PMID:22003954

  6. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    Science.gov (United States)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  7. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain.

    Science.gov (United States)

    Satchell, Karla J F; Jones, Christopher J; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H

    2016-09-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. PMID:27297393

  8. A beamformer analysis of MEG data reveals frontal generators of the musically elicited mismatch negativity.

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    Claudia Lappe

    Full Text Available To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM on magnetoencephalography (MEG data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20% by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC, inferior frontal (IFC, superior frontal (SFC and orbitofrontal (OFC cortices within a time window of 100-200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG, optical imaging and functional magnetic resonance imaging (fMRI studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.

  9. Transcriptome-wide Analysis Of Vernalization Reveals Conserved and Species-specific Mechanisms in Brachypodium

    Institute of Scientific and Technical Information of China (English)

    Qing Huan; Zhiwei Mao; Jingyu Zhang; Yunyuan Xu; Kang Chong

    2013-01-01

    Several temperate cereals need vernalization to promote flowering.Little,however,is known about the vernalization-memory-related genes,and almost no comparative analysis has been performed.Here,RNA-Seq was used for transcriptome analysis in non-vernalized,vernalized and post-vernalized Brachypodium distachyon (L.) Beauv.seedlings.In total,the expression of 1,665 genes showed significant changes (fold change ≥4) in response to vernalization.Among them,674 putative vernalization-memory-related genes with a constant response to vernalization were significantly enriched in transcriptional regulation and monooxygenase-mediated biological processes.Comparative analysis of vernalization-memory-related genes with barley demonstrated that the oxidative-stress response was the most conserved pathway between these two plant species.Moreover,Brachypodium preferred to regulate transcription and protein phosphorylation processes,while vernalization-memory-related genes,whose products are cytoplasmic membrane-bound-vesicle-located proteins,were preferred to be regulated in barley.Correlation analysis of the vernalization-related genes with barley revealed that the vernalization mechanism was conserved between these two plant species.In summary,vernalization,including its memory mechanism,is conserved between Brachypodium and barley,although several species-specific features also exist.The data reported here will provide primary resources for subsequent functional research in vernalization.

  10. Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.

    Science.gov (United States)

    Mizuno, Satoshi; Ogishima, Soichi; Kitatani, Kazuyuki; Kikuchi, Masataka; Tanaka, Hiroshi; Yaegashi, Nobuo; Nakaya, Jun

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of senile dementia. Many inflammatory factors such as amyloid-β and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named "AlzPathway," a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1) ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2) several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD. PMID:26849355

  11. Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Satoshi Mizuno

    Full Text Available Alzheimer's disease (AD is the most common cause of senile dementia. Many inflammatory factors such as amyloid-β and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named "AlzPathway," a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1 ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2 several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD.

  12. 樱桃汁和草莓汁激活Nrf2信号通路对砷诱导的人支气管上皮细胞损伤的保护作用%Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孔得刚; 王莉莉; 周洪雷; 任冬梅; 娄红祥; 沈涛

    2014-01-01

    ),and then antioxi-dant response element(ARE)luciferase reporter gene assay and Western blotting analysis were adopted for screening and identification of juice on Nrf2 signaling pathway;HBE cells were randomly divided into the control group,sul-foraphen treated group,and juice treated groups (juice dilution ratios were 1∶10,1∶20,and 1∶40,respectively),and then the QuantiChrom glutathione (GSH)assay kit were used to detect the intracellular GSH levels;MTT assay and cell trans-fection were carried out to evaluate their protection effects against arsenic-induced toxicity in HBE cells.Results Juices of cherry and strawberry increased the luciferase activity in a dose-dependent manner,enhanced the protein expression of Nrf2 and its downstream genes NADPH:quinone oxidoreduefase Ⅰ(NQO1 )and gamma glutamyl cysteine synthetase (γGCS)in MDA-MB-231 cells,and up-regulated the intracellular GSH levels in HBE cells.Co-treatment with juice and arsenic evidently improved HBE cell survival in response to arsenic treatment alone,while the juices no longer pro-tected the HBE cells whose Nrf2 expression was koncked down by Nrf2-siRNA.Conclusion Juices of cherry and strawberry confer the protection effects on HBE cells against arsenic-induced toxicity in a Nrf2-dependent manner.

  13. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure.

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    Nicolas M Berbenetz

    2010-09-01

    Full Text Available Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers positions nucleosomes adjacent to the origin to promote replication origin function.

  14. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

    Directory of Open Access Journals (Sweden)

    E. Damaraju

    2014-01-01

    Full Text Available Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length, and a dynamic sense, computed using sliding windows (44 s in length and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual, as well as reduced connectivity (hypoconnectivity between sensory networks from all modalities. Dynamic analysis suggests that (1, on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2, that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity

  15. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  16. Phototaxis of Haloarcula marismortui revealed through a novel microbial motion analysis algorithm.

    Science.gov (United States)

    Lin, Yu-Cheng; Fu, Hsu-Yuan; Yang, Chii-Shen

    2010-01-01

    Haloarcula marismortui has been described to be nonmotile prior to the recent identification of flagellar filaments, suggesting the motile nature of H. marismortui. Here we observed the locomotion of freshly cultured H. marismortui cells and tracked the swimming trajectories via ImageJ. Trajectories of H. marismortui are intrinsically noisy, posing difficulties in motion analysis with previously established algorithms. By introducing the concept of "window vector," a Microsoft Excel-VBA-implemented microbial motion analysis algorithm reported here was able to (1) discriminate nonswimming objects from swimming cells without empirical customization by applying a power-law relationship and (2) reduce the noise caused by Brownian motion, thus enhancing the accuracy of swim reversal identification. Based on this motion analysis algorithm, two recently identified sensory rhodopsins, HmSRI and HmSRII, were shown to mediate photoattractant and photorepellent responses, respectively, revealing the phototactic activity of H. marismortui, the only archaeon showing such phenomenon other than Halobacterium salinarum. PMID:20553410

  17. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  18. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

    Science.gov (United States)

    Li, Yue; Zhang, Zhaolei

    2014-11-01

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  19. Rapid genome evolution in Pms1 region of rice revealed by comparative sequence analysis

    Institute of Scientific and Technical Information of China (English)

    YU JinSheng; FAN YouRong; LIU Nan; SHAN Yan; LI XiangHua; ZHANG QiFa

    2007-01-01

    Pms1, a locus for photoperiod sensitive genic male sterility in rice, was identified and mapped to chromosome 7 in previous studies. Here we report an effort to identify the candidate genes for Pms1 by comparative sequencing of BAC clones from two cultivars Minghui 63 and Nongken 58, the parents for the initial mapping population. Annotation and comparison of the sequences of the two clones resulted in a total of five potential candidates which should be functionally tested. We also conducted comparative analysis of sequences of these two cultivars with two other cultivars, Nipponbare and 93-11,for which sequence data were available in public databases. The analysis revealed large differences in sequence composition among the four genotypes in the Pms1 region primarily due to retroelement activity leading to rapid recent growth and divergence of the genomes. High levels of polymorphism in the forms of indels and SNPs were found both in intra- and inter-subspecific comparisons. Dating analysis using LTRs of the retroelements in this region showed that the substitution rate of LTRs was much higher than reported in the literature. The results provided strong evidence for rapid genomic evolution of this region as a consequence of natural and artificial selection.

  20. Meta-Analysis of EMT Datasets Reveals Different Types of EMT

    Science.gov (United States)

    Zhang, Wei; Zhang, Mengdan; Yang, Xiao; Kuang, Rui; Zheng, Hui

    2016-01-01

    As a critical process during embryonic development, cancer progression and cell fate conversions, epithelial-mesenchymal transition (EMT) has been extensively studied over the last several decades. To further understand the nature of EMT, we performed meta-analysis of multiple microarray datasets to identify the related generic signature. In this study, 24 human and 17 mouse microarray datasets were integrated to identify conserved gene expression changes in different types of EMT. Our integrative analysis revealed that there is low agreement among the list of the identified signature genes and three other lists in previous studies. Since removing the datasets with weakly-induced EMT from the analysis did not significantly improve the overlapping in the signature-gene lists, we hypothesized the existence of different types of EMT. This hypothesis was further supported by the grouping of 74 human EMT-induction samples into five distinct clusters, and the identification of distinct pathways in these different clusters of EMT samples. The five clusters of EMT-induction samples also improves the understanding of the characteristics of different EMT types. Therefore, we concluded the existence of different types of EMT was the possible reason for its complex role in multiple biological processes. PMID:27258544

  1. Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

    Science.gov (United States)

    Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

    2015-11-01

    Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

  2. Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes

    Science.gov (United States)

    Jacob, Yael; Winetraub, Yonatan; Raz, Gal; Ben-Simon, Eti; Okon-Singer, Hadas; Rosenberg-Katz, Keren; Hendler, Talma; Ben-Jacob, Eshel

    2016-01-01

    Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network’s hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions. PMID:27271458

  3. Genetic analysis reveals candidate species in the Scinax catharinae clade (Amphibia: Anura) from Central Brazil.

    Science.gov (United States)

    Nogueira, Lídia; Solé, Mirco; Siqueira, Sérgio; Affonso, Paulo Roberto Antunes de Mello; Strüssmann, Christine; Sampaio, Iracilda

    2016-03-01

    Scinax (Anura: Hylidae) is a species-rich genus of amphibians (113 spp.), divided into five species groups by morphological features. Cladistic analyses however revealed only two monophyletic clades in these groups: Scinax catharinae and Scinax ruber. Most species from the S. catharinae clade are found in Atlantic rainforest, except for Scinax canastrensis,S. centralis, S. luizotavioi, S. machadoi,S. pombali and S. skaios. In the present work, specimens of Scinax collected in Chapada dos Guimarães, central Brazil, were morphologically compatible with species from theS. catharinae group. On the other hand, genetic analysis based on mitochondrial (16S and 12S) and nuclear (rhodopsin) sequences revealed a nucleotide divergence of 6 to 20% between Scinax sp. and other congeners from the Brazilian savannah (Cerrado). Accordingly, Bayesian inference placed Scinax sp. in the S. catharinae clade with high support values. Hence, these findings strongly indicate the presence of a new species in the S. catharinae clade from the southwestern portion of the Brazilian savannah. To be properly validated as a novel species, detailed comparative morphological and bioacustic studies with other taxa from Brazil such asS. canastrensis, S. centralis, S. luizotavioi, S. machadoi, S. pombali and S. skaios are required. PMID:27007898

  4. Stable isotope analysis of vertebrae reveals ontogenetic changes in habitat in an endothermic pelagic shark.

    Science.gov (United States)

    Carlisle, Aaron B; Goldman, Kenneth J; Litvin, Steven Y; Madigan, Daniel J; Bigman, Jennifer S; Swithenbank, Alan M; Kline, Thomas C; Block, Barbara A

    2015-01-22

    Ontogenetic changes in habitat are driven by shifting life-history requirements and play an important role in population dynamics. However, large portions of the life history of many pelagic species are still poorly understood or unknown. We used a novel combination of stable isotope analysis of vertebral annuli, Bayesian mixing models, isoscapes and electronic tag data to reconstruct ontogenetic patterns of habitat and resource use in a pelagic apex predator, the salmon shark (Lamna ditropis). Results identified the North Pacific Transition Zone as the major nursery area for salmon sharks and revealed an ontogenetic shift around the age of maturity from oceanic to increased use of neritic habitats. The nursery habitat may reflect trade-offs between prey availability, predation pressure and thermal constraints on juvenile endothermic sharks. The ontogenetic shift in habitat coincided with a reduction of isotopic niche, possibly reflecting specialization upon particular prey or habitats. Using tagging data to inform Bayesian isotopic mixing models revealed that adult sharks primarily use neritic habitats of Alaska yet receive a trophic subsidy from oceanic habitats. Integrating the multiple methods used here provides a powerful approach to retrospectively study the ecology and life history of migratory species throughout their ontogeny. PMID:25621332

  5. Precursors of stall and surge processes in gas turbines revealed by wavelet analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dremin, I.M.; Ivanov, O.V.; Nechitailo, V.A. [P.N. Lebedev Physical Institute, Moscow (Russian Federation); Furletov, V.I. [Central Institute for Aviation Motors, Moscow (Russian Federation); Terziev, V.G. [TEKO, Moscow (Russian Federation)

    2002-06-01

    Multiresolution wavelet analysis of pressure variations in a gas turbine compressor reveals the existence of precursors of stall and surge processes. Signals from eight pressure sensors positioned at various places within the compressor were recorded and digitized in three different operating modes in stationary conditions with a recording interval of 1 ms during 5-6 s. It has been discovered that there exists a scale of 32 intervals over which the dispersion (variance) of the wavelet coefficients shows a remarkable drop of about 40% for more than 1 s prior to the development of the malfunction. A shuffled sample of the same values of the pressure does not show such a drop demonstrating the dynamical origin of this effect. Higher order correlation moments reveal different slopes in these two regions differing by the variance values. The log-log dependence of the moments does not show clear fractal behavior because the scales of 16 and 32 intervals are not on the straight line of monofractals. This is a clear indication of the nonlinear response of the system at this scale. These results provide a means for automatic regulation of an engine, preventing possible failures. (author)

  6. Bifidobacterium asteroides PRL2011 genome analysis reveals clues for colonization of the insect gut.

    Directory of Open Access Journals (Sweden)

    Francesca Bottacini

    Full Text Available Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration.

  7. Lateral spreading in the Svecofennian mid-crust revealed by seismic attribute analysis

    DEFF Research Database (Denmark)

    Torvela, Taija; Moreau, Julien; Butler, Robert;

    orogen. Details of this spreading are, however, still not clear. The Svecofennian crust is imaged by the Finnish Reflection Experiment (FIRE) that was designed to image the major crustal structures in Finland. Here, we show an example of how seismic attributes, combined with the seismic facies...... interpretation technique, can be used to enhance the FIRE data. We focussed our study to the West Uusimaa complex WUC, where the middle crust of the Svecofennian is exposed. We compare the interpreted, enhanced seismic data with field observations. The attribute analysis of the seismic data reveals......In orogenic belts, crustal thickening precedes rheological weakening of the middle and lower orogenic crust leading to lateral spreading and, ultimately, to collapse of an orogen. Recent studies have implied similar development in the middle crust during the Palaeoproterozoic composite Svecofennian...

  8. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-07-15

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology.

  9. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  10. Anomalous dispersion of Lagrangian particles in local regions of turbulent flows revealed by convex hull analysis

    CERN Document Server

    Pratt, J; Mueller, W -C; Chapman, S C; Watkins, N W

    2014-01-01

    Local regions of anomalous particle dispersion, and intermittent events that occur in turbulent flows can greatly influence the global statistical description of the flow. These local behaviors can be identified and analyzed by comparing the growth of neighboring convex hulls of Lagrangian tracer particles. Although in our simulations of homogeneous turbulence the convex hulls generally grow in size, after the Lagrangian particles that define the convex hulls begin to disperse, our analysis reveals short periods when the convex hulls of the Lagrangian particles shrink, evidence that particles are not dispersing simply. Shrinkage can be associated with anisotropic flows, since it occurs most frequently in the presence of a mean magnetic field or thermal convection. We compare dispersion between a wide range of statistically homogeneous and stationary turbulent flows ranging from homogeneous isotropic Navier-Stokes turbulence over different configurations of magnetohydrodynamic turbulence and Boussinesq convect...

  11. Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis

    Science.gov (United States)

    Vogel, Robert M.; Erez, Amir; Altan-Bonnet, Grégoire

    2016-01-01

    Despite progress in drug development, a quantitative and physiological understanding of how small-molecule inhibitors act on cells is lacking. Here, we measure the signalling and proliferative response of individual primary T-lymphocytes to a combination of antigen, cytokine and drug. We uncover two distinct modes of signalling inhibition: digital inhibition (the activated fraction of cells diminishes upon drug treatment, but active cells appear unperturbed), versus analogue inhibition (the activated fraction is unperturbed whereas activation response is diminished). We introduce a computational model of the signalling cascade that accounts for such inhibition dichotomy, and test the model predictions for the phenotypic variability of cellular responses. Finally, we demonstrate that the digital/analogue dichotomy of cellular response as revealed on short (signal transduction) timescales, translates into similar dichotomy on longer (proliferation) timescales. Our single-cell analysis of drug action illustrates the strength of quantitative approaches to translate in vitro pharmacology into functionally relevant cellular settings. PMID:27687249

  12. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    Science.gov (United States)

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  13. Metabolomic analysis reveals metabolic disturbance in the cortex and hippocampus of subchronic MK-801 treated rats.

    Directory of Open Access Journals (Sweden)

    Liya Sun

    Full Text Available BACKGROUND: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia. METHODS: Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations. RESULTS: Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2X = 0.441, Q(2Y = 0.413 and R(2X = 0.698, Q(2Y = 0.677, respectively. The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment. CONCLUSIONS: Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to

  14. Partial sequencing of the bottle gourd genome reveals markers useful for phylogenetic analysis and breeding

    Directory of Open Access Journals (Sweden)

    Wang Sha

    2011-09-01

    Full Text Available Abstract Background Bottle gourd [Lagenaria siceraria (Mol. Standl.] is an important cucurbit crop worldwide. Archaeological research indicates that bottle gourd was domesticated more than 10,000 years ago, making it one of the earliest plants cultivated by man. In spite of its widespread importance and long history of cultivation almost nothing has been known about the genome of this species thus far. Results We report here the partial sequencing of bottle gourd genome using the 454 GS-FLX Titanium sequencing platform. A total of 150,253 sequence reads, which were assembled into 3,994 contigs and 82,522 singletons were generated. The total length of the non-redundant singletons/assemblies is 32 Mb, theoretically covering ~ 10% of the bottle gourd genome. Functional annotation of the sequences revealed a broad range of functional types, covering all the three top-level ontologies. Comparison of the gene sequences between bottle gourd and the model cucurbit cucumber (Cucumis sativus revealed a 90% sequence similarity on average. Using the sequence information, 4395 microsatellite-containing sequences were identified and 400 SSR markers were developed, of which 94% amplified bands of anticipated sizes. Transferability of these markers to four other cucurbit species showed obvious decline with increasing phylogenetic distance. From analyzing polymorphisms of a subset of 14 SSR markers assayed on 44 representative China bottle gourd varieties/landraces, a principal coordinates (PCo analysis output and a UPGMA-based dendrogram were constructed. Bottle gourd accessions tended to group by fruit shape rather than geographic origin, although in certain subclades the lines from the same or close origin did tend to cluster. Conclusions This work provides an initial basis for genome characterization, gene isolation and comparative genomics analysis in bottle gourd. The SSR markers developed would facilitate marker assisted breeding schemes for efficient

  15. Comparative transcriptomic analysis reveals similarities and dissimilarities in Saccharomyces cerevisiae wine strains response to nitrogen availability.

    Directory of Open Access Journals (Sweden)

    Catarina Barbosa

    Full Text Available Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23, under low (67 mg/L and high nitrogen (670 mg/L regimes, at three time points during fermentation (12 h, 24 h and 96 h. Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12 h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this

  16. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve

    Science.gov (United States)

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

  17. Metagenomic analysis reveals symbiotic relationship among bacteria in Microcystis-dominated community

    Directory of Open Access Journals (Sweden)

    Meili eXie

    2016-02-01

    Full Text Available Microcystis bloom, a cyanobacterial mass occurrence often found in eutrophicated water bodies, is one of the most serious threats to freshwater ecosystems worldwide. In nature, Microcystis forms aggregates or colonies that contain heterotrophic bacteria. The Microcystis-bacteria colonies were persistent even when they were maintained in lab culture for a long period. The relationship between Microcystis and the associated bacteria was investigated by a metagenomic approach in this study. We developed a visualization-guided method of binning for genome assembly after total colony DNA sequencing. We found that the method was effective in grouping sequences and it did not require reference genome sequence. Individual genomes of the colony bacteria were obtained and they provided valuable insights into microbial community structures. Analysis of metabolic pathways based on these genomes revealed that while all heterotrophic bacteria were dependent upon Microcystis for carbon and energy, Vitamin B12 biosynthesis, which is required for growth by Microcystis, was accomplished in a cooperative fashion among the bacteria. Our analysis also suggests that individual bacteria in the colony community contributed a complete pathway for degradation of benzoate, which is inhibitory to the cyanobacterial growth, and its ecological implication for Microcystis bloom is discussed.

  18. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    Science.gov (United States)

    Wu, Dan; Kendrick, Keith M; Levitin, Daniel J; Li, Chaoyi; Yao, Dezhong

    2015-01-01

    Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart. PMID:26545104

  19. Expression analysis of five zebrafish RXFP3 homologues reveals evolutionary conservation of gene expression pattern.

    Science.gov (United States)

    Donizetti, Aldo; Fiengo, Marcella; Iazzetti, Giovanni; del Gaudio, Rosanna; Di Giaimo, Rossella; Pariante, Paolo; Minucci, Sergio; Aniello, Francesco

    2015-01-01

    Relaxin peptides exert different functions in reproduction and neuroendocrine processes via interaction with two evolutionarily unrelated groups of receptors: RXFP1 and RXFP2 on one hand, RXFP3 and RXFP4 on the other hand. Evolution of receptor genes after splitting of tetrapods and teleost lineage led to a different retention rate between mammals and fish, with the latter having more gene copies compared to the former. In order to improve our knowledge on the evolution of the relaxin ligands/receptors system and have insights on their function in early stages of life, in the present paper we analyzed the expression pattern of five zebrafish RXFP3 homologue genes during embryonic development. In our analysis, we show that only two of the five genes are expressed during embryogenesis and that their transcripts are present in all the developmental stages. Spatial localization analysis of these transcripts revealed that the gene expression is restricted in specific territories starting from early pharyngula stage. Both genes are expressed in the brain but in different cell clusters and in extra-neural territories, one gene in the interrenal gland and the other in the pancreas. These two genes share expression territories with the homologue mammalian counterpart, highlighting a general conservation of gene expression regulatory processes and their putative function during evolution that are established early in vertebrate embryogenesis. PMID:25384467

  20. Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes.

    Science.gov (United States)

    Subirats, Jéssica; Sànchez-Melsió, Alexandre; Borrego, Carles M; Balcázar, José Luis; Simonet, Pascal

    2016-08-01

    A metagenomics approach was applied to explore the presence of antibiotic resistance genes (ARGs) in bacteriophages from hospital wastewater. Metagenomic analysis showed that most phage sequences affiliated to the order Caudovirales, comprising the tailed phage families Podoviridae, Siphoviridae and Myoviridae. Moreover, the relative abundance of ARGs in the phage DNA fraction (0.26%) was higher than in the bacterial DNA fraction (0.18%). These differences were particularly evident for genes encoding ATP-binding cassette (ABC) and resistance-nodulation-cell division (RND) proteins, phosphotransferases, β-lactamases and plasmid-mediated quinolone resistance. Analysis of assembled contigs also revealed that blaOXA-10, blaOXA-58 and blaOXA-24 genes belonging to class D β-lactamases as well as a novel blaTEM (98.9% sequence similarity to the blaTEM-1 gene) belonging to class A β-lactamases were detected in a higher proportion in phage DNA. Although preliminary, these findings corroborate the role of bacteriophages as reservoirs of resistance genes and thus highlight the necessity to include them in future studies on the emergence and spread of antibiotic resistance in the environment.

  1. Transcriptome analysis reveals dynamic changes in the gene expression of tobacco seedlings under low potassium stress

    Indian Academy of Sciences (India)

    Liming Lu; Yong Chen; Lin Lu; Yifei Lu; Liqin Li

    2015-09-01

    Potassium plays a key role in plant development and reproduction. In agricultural practice, potassium deficiency is common worldwide, and leads to crop growth inhibition and output reduction. In this study, we analysed the transcriptome of tobacco seedlings under low potassium stress. Tobacco seedlings with or without decreased potassium treatment were harvested after 0 (control), 6, 12, or 24 h and were submitted for microarray analysis. The results showed that up to 3790 genes were upregulated or downregulated more than 2-fold as a result of the decreased potassium treatment. Gene ontology analysis revealed significantly differentially expressed genes that were categorized as cation binding, transcription regulation, metabolic processes, transporter activity and enzyme regulation. Some potassium, nitrogen and phosphorus transporters; transcription factors; and plant signal molecules, such as CPKs were also significantly differentially expressed under potassium deficiency. Our results indicate that the expression profiles of a large number of genes involved in various plant physiological processes are significantly altered in response to potassium deficiency, which can result in physiological and morphological changes in tobacco plants.

  2. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    Science.gov (United States)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; M. Maloney, Cliona; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P.R.; Mehta, Amar; van Iperen, Erik P.A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M.A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; Boer, Anthonius de; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E.K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; J. Meyer, Nuala; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W.M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I.W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; D. Christie, Jason; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F.A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. PMID:21194676

  3. Comparative Metagenomic Analysis Reveals Mechanisms for Stress Response in Hypoliths from Extreme Hyperarid Deserts.

    Science.gov (United States)

    Le, Phuong Thi; Makhalanyane, Thulani P; Guerrero, Leandro D; Vikram, Surendra; Van de Peer, Yves; Cowan, Don A

    2016-01-01

    Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the two metagenomes were identified. The Antarctic hypolithic metagenome displayed a high number of sequences assigned to sigma factors, replication, recombination and repair, translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significant divergence in the genetic determinants of amino acid and nucleotide metabolism between these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes. PMID:27503299

  4. Multifractal analysis of Barkhausen noise reveals the dynamic nature of criticality at hysteresis loop

    Science.gov (United States)

    Tadić, Bosiljka

    2016-06-01

    The field-driven magnetisation reversal processes in disordered systems exhibit a collective behaviour that is manifested in the scale-invariance of avalanches, closely related to underlying dynamical mechanisms. Using the multifractal time series analysis, we study the structure of fluctuations at different scales in the accompanying Barkhausen noise. The stochastic signal represents the magnetisation discontinuities along the hysteresis loop of a three-dimensional random field Ising model simulated for varied disorder strength and driving rates. The analysis of the spectrum of the generalised Hurst exponents reveals that the dominant segments of the signal with large fluctuations represent two distinct classes of stochastic processes in weak and strong pinning regimes. Furthermore, in the weak pinning regime, the part of the signal originating from the beginning of the hysteresis loop has a different multifractal spectrum than the signal near the coercive field. The enhanced fluctuations (primarily in the central part of the hysteresis loop) for increased driving rate and larger system size, lead to a further broadening of the spectrum. The analysed Barkhausen signals are also shown to exhibit temporal correlations and power-law distributions of the magnetisation discontinuity and avalanche sizes, in agreement with previous studies. The multifractal properties of Barkhausen noise describe the dynamical state of domains and precisely discriminate the weak pinning, permitting the motion of individual walls, from the mechanisms occurring in strongly disordered systems.

  5. DNA polymorphisms in banana and sugar cane varieties revealed by RAPD analysis

    International Nuclear Information System (INIS)

    Sugar cane is the fourth most important cash crop of Pakistan and is grown on 1 million hectares of land, with a total production of 37 million tonnes. It does not flower under existing environmental conditions. Sugar cane is vegetatively propagated and the national breeding programmes is restricted to the adaptation and multiplication of exotic varieties. Random amplified polymorphic DNA (RAPD) markers were used to establish polymorphisms among various local sugar cane varieties. DNA from the varieties L-118, L-116, BL-4, BF-162, Col-44, Col-54, Triton and Puri was isolated and amplified by polymerase chain reaction using ten nucleotide primers. The amplification profiles of all the sugar cane varieties were compared and the polymorphisms detected. DNA was isolated from the embryogenic calli of sugar cane subjected to gamma irradiation at different doses (0, 0.5, 2.0, 4.0 and 6.0 krad) and salt stresses (NaCl: 0, 50, 100, 150 and 200 mM), and was amplified with random primers to detect the polymorphisms introduced by stress. The banana is another important vegetatively propagated crop in Pakistan. DNA isolation from micropropagated banana was optimized and RAPD analysis performed on several clones of the banana variety Williams. The level of genetic variability revealed from calli and vegetatively propagated sugar cane and banana by RAPD analysis is discussed. (author). 10 refs, 5 figs, 2 tabs

  6. Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays

    Directory of Open Access Journals (Sweden)

    Domenico F. Galati

    2016-01-01

    Full Text Available Multi-ciliated cells (MCCs use polarized fields of undulating cilia (ciliary array to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs that are arranged within a spatially complex 3-dimensional geometry (3D. Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs.

  7. Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes.

    Science.gov (United States)

    Subirats, Jéssica; Sànchez-Melsió, Alexandre; Borrego, Carles M; Balcázar, José Luis; Simonet, Pascal

    2016-08-01

    A metagenomics approach was applied to explore the presence of antibiotic resistance genes (ARGs) in bacteriophages from hospital wastewater. Metagenomic analysis showed that most phage sequences affiliated to the order Caudovirales, comprising the tailed phage families Podoviridae, Siphoviridae and Myoviridae. Moreover, the relative abundance of ARGs in the phage DNA fraction (0.26%) was higher than in the bacterial DNA fraction (0.18%). These differences were particularly evident for genes encoding ATP-binding cassette (ABC) and resistance-nodulation-cell division (RND) proteins, phosphotransferases, β-lactamases and plasmid-mediated quinolone resistance. Analysis of assembled contigs also revealed that blaOXA-10, blaOXA-58 and blaOXA-24 genes belonging to class D β-lactamases as well as a novel blaTEM (98.9% sequence similarity to the blaTEM-1 gene) belonging to class A β-lactamases were detected in a higher proportion in phage DNA. Although preliminary, these findings corroborate the role of bacteriophages as reservoirs of resistance genes and thus highlight the necessity to include them in future studies on the emergence and spread of antibiotic resistance in the environment. PMID:27312355

  8. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions

    Science.gov (United States)

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I.; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B. H.

    2016-05-01

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions.

  9. Glycoproteomic Analysis of Seven Major Allergenic Proteins Reveals Novel Post-translational Modifications*

    Science.gov (United States)

    Halim, Adnan; Carlsson, Michael C.; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y.; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L.; Wandall, Hans H.

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM1 characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines. PMID:25389185

  10. Glycoproteomic analysis of seven major allergenic proteins reveals novel post-translational modifications.

    Science.gov (United States)

    Halim, Adnan; Carlsson, Michael C; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L; Wandall, Hans H

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM(1) characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines.

  11. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    Directory of Open Access Journals (Sweden)

    Dan Wu

    Full Text Available Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  12. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions

    Science.gov (United States)

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I.; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B. H.

    2016-01-01

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions. PMID:27193869

  13. Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

    Directory of Open Access Journals (Sweden)

    Faure Claudine

    2007-10-01

    Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

  14. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus).

    Science.gov (United States)

    Dowling, Thomas E; Turner, Thomas F; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Marsh, Paul C

    2014-03-01

    Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is maintained by harvesting naturally produced larvae from the lake, rearing them in protective custody, and repatriating them at sizes less vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized for sequential larval cohorts collected over a 15-year time series revealed no changes in geographic structuring but indicated significant increase in mtDNA diversity for the entire population over time. Likewise, ratios of annual effective breeders to annual census size (N b /N a) increased significantly despite sevenfold reduction of N a. These results indicated that conservation actions diminished near-term extinction risk due to genetic factors and should now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term risks. More generally, time-series analysis permitted robust testing of trends in genetic diversity, despite low precision of some metrics. PMID:24665337

  15. Principal Component Analysis reveals correlation of cavities evolution and functional motions in proteins.

    Science.gov (United States)

    Desdouits, Nathan; Nilges, Michael; Blondel, Arnaud

    2015-02-01

    Protein conformation has been recognized as the key feature determining biological function, as it determines the position of the essential groups specifically interacting with substrates. Hence, the shape of the cavities or grooves at the protein surface appears to drive those functions. However, only a few studies describe the geometrical evolution of protein cavities during molecular dynamics simulations (MD), usually with a crude representation. To unveil the dynamics of cavity geometry evolution, we developed an approach combining cavity detection and Principal Component Analysis (PCA). This approach was applied to four systems subjected to MD (lysozyme, sperm whale myoglobin, Dengue envelope protein and EF-CaM complex). PCA on cavities allows us to perform efficient analysis and classification of the geometry diversity explored by a cavity. Additionally, it reveals correlations between the evolutions of the cavities and structures, and can even suggest how to modify the protein conformation to induce a given cavity geometry. It also helps to perform fast and consensual clustering of conformations according to cavity geometry. Finally, using this approach, we show that both carbon monoxide (CO) location and transfer among the different xenon sites of myoglobin are correlated with few cavity evolution modes of high amplitude. This correlation illustrates the link between ligand diffusion and the dynamic network of internal cavities.

  16. Bioinformatic analysis of the neprilysin (M13 family of peptidases reveals complex evolutionary and functional relationships

    Directory of Open Access Journals (Sweden)

    Pinney John W

    2008-01-01

    Full Text Available Abstract Background The neprilysin (M13 family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2, which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. Results The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates

  17. Time series analysis of satellite data reveals continuous deforestation of New England since the 1980s

    Science.gov (United States)

    Olofsson, Pontus; Holden, Christopher E.; Bullock, Eric L.; Woodcock, Curtis E.

    2016-06-01

    Land cover and land change were monitored continuously between 1985 and 2011 at 30 m resolution across New England in the Northeastern United States in support of modeling the terrestrial carbon budget. It was found that the forest area has been decreasing throughout the study period in each state of the region since the 1980s. A total of 386 657 ± 98 137 ha (95% confidence interval) of forest has been converted to other land covers since 1985. Mainly driven by low density residential development, the deforestation accelerated in the mid-1990s until 2007 when it plateaued as a result of declining new residential construction and in turn, the financial crisis of 2007–08. The area of forest harvest, estimated at 226 519 ± 66 682 ha, was mapped separately and excluded from the deforestation estimate, while the area of forest expansion on non-forested lands was found to not be significantly different from zero. New England is often held as a principal example of a forest transition with historical widespread deforestation followed by recovery of forestlands as farming activities diminished, but the results of this study support the notion of a reversal of the forest transition as the region again is experiencing widespread deforestation. All available Landsat imagery acquired after 1985 for the study area were collected and used in the analysis. Areas of land cover and land change were estimated from a random sample of reference observations stratified by a twelve-class land change map encompassing the entire study area and period. The statistical analysis revealed that the net change in forest area and the associated modeled impact on the terrestrial carbon balance would have been considerably different if the results of the map were used without inferring the area of forest change by analysis of a reference sample.

  18. Co-expression network analysis reveals transcription factors associated to cell wall biosynthesis in sugarcane.

    Science.gov (United States)

    Ferreira, Savio Siqueira; Hotta, Carlos Takeshi; Poelking, Viviane Guzzo de Carli; Leite, Debora Chaves Coelho; Buckeridge, Marcos Silveira; Loureiro, Marcelo Ehlers; Barbosa, Marcio Henrique Pereira; Carneiro, Monalisa Sampaio; Souza, Glaucia Mendes

    2016-05-01

    Sugarcane is a hybrid of Saccharum officinarum and Saccharum spontaneum, with minor contributions from other species in Saccharum and other genera. Understanding the molecular basis of cell wall metabolism in sugarcane may allow for rational changes in fiber quality and content when designing new energy crops. This work describes a comparative expression profiling of sugarcane ancestral genotypes: S. officinarum, S. spontaneum and S. robustum and a commercial hybrid: RB867515, linking gene expression to phenotypes to identify genes for sugarcane improvement. Oligoarray experiments of leaves, immature and intermediate internodes, detected 12,621 sense and 995 antisense transcripts. Amino acid metabolism was particularly evident among pathways showing natural antisense transcripts expression. For all tissues sampled, expression analysis revealed 831, 674 and 648 differentially expressed genes in S. officinarum, S. robustum and S. spontaneum, respectively, using RB867515 as reference. Expression of sugar transporters might explain sucrose differences among genotypes, but an unexpected differential expression of histones were also identified between high and low Brix° genotypes. Lignin biosynthetic genes and bioenergetics-related genes were up-regulated in the high lignin genotype, suggesting that these genes are important for S. spontaneum to allocate carbon to lignin, while S. officinarum allocates it to sucrose storage. Co-expression network analysis identified 18 transcription factors possibly related to cell wall biosynthesis while in silico analysis detected cis-elements involved in cell wall biosynthesis in their promoters. Our results provide information to elucidate regulatory networks underlying traits of interest that will allow the improvement of sugarcane for biofuel and chemicals production. PMID:26820137

  19. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

    Directory of Open Access Journals (Sweden)

    Hong Hao

    Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

  20. Time series analysis of satellite data reveals continuous deforestation of New England since the 1980s

    Science.gov (United States)

    Olofsson, Pontus; Holden, Christopher E.; Bullock, Eric L.; Woodcock, Curtis E.

    2016-06-01

    Land cover and land change were monitored continuously between 1985 and 2011 at 30 m resolution across New England in the Northeastern United States in support of modeling the terrestrial carbon budget. It was found that the forest area has been decreasing throughout the study period in each state of the region since the 1980s. A total of 386 657 ± 98 137 ha (95% confidence interval) of forest has been converted to other land covers since 1985. Mainly driven by low density residential development, the deforestation accelerated in the mid-1990s until 2007 when it plateaued as a result of declining new residential construction and in turn, the financial crisis of 2007-08. The area of forest harvest, estimated at 226 519 ± 66 682 ha, was mapped separately and excluded from the deforestation estimate, while the area of forest expansion on non-forested lands was found to not be significantly different from zero. New England is often held as a principal example of a forest transition with historical widespread deforestation followed by recovery of forestlands as farming activities diminished, but the results of this study support the notion of a reversal of the forest transition as the region again is experiencing widespread deforestation. All available Landsat imagery acquired after 1985 for the study area were collected and used in the analysis. Areas of land cover and land change were estimated from a random sample of reference observations stratified by a twelve-class land change map encompassing the entire study area and period. The statistical analysis revealed that the net change in forest area and the associated modeled impact on the terrestrial carbon balance would have been considerably different if the results of the map were used without inferring the area of forest change by analysis of a reference sample.

  1. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells.

    Science.gov (United States)

    Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas; Lyon, David; Mullari, Meeli; Madsen, Maria V; Daniel, Jeremy A; Jensen, Lars J; Nielsen, Michael L

    2016-01-01

    The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified by methylation. Through quantitative proteomics and RNA interference to examine arginine methylation stoichiometry, we unexpectedly found that the protein arginine methyltransferase (PRMT) family of arginine methyltransferases catalyzed methylation independently of arginine sequence context. In contrast to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially regulated the functions of the pre-mRNA splicing factor SRSF2 (serine/arginine-rich splicing factor 2) and the RNA transport ribonucleoprotein HNRNPUL1 (heterogeneous nuclear ribonucleoprotein U-like 1). Knocking down PRMT5 impaired the RNA binding function of SRSF2, whereas knocking down PRMT4 [also known as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human arginine methylome provides a missing piece in the global and integrative view of cellular physiology and protein regulation. PMID:27577262

  2. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.

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    Peter Hevezi

    Full Text Available Efforts to unravel the mechanisms underlying taste sensation (gustation have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM procured fungiform (FG and circumvallate (CV taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology.

  3. Secretome analysis of Aspergillus fumigatus reveals Asp-hemolysin as a major secreted protein.

    Science.gov (United States)

    Wartenberg, Dirk; Lapp, Katrin; Jacobsen, Ilse D; Dahse, Hans-Martin; Kniemeyer, Olaf; Heinekamp, Thorsten; Brakhage, Axel A

    2011-11-01

    Surface-associated and secreted proteins represent primarily exposed components of Aspergillus fumigatus during host infection. Several secreted proteins are known to be involved in defense mechanisms or immune evasion, thus, probably contributing to pathogenicity. Furthermore, several secreted antigens were identified as possible biomarkers for the verification of diseases caused by Aspergillus species. Nevertheless, there is only limited knowledge about the composition of the secretome and about molecular functions of particular proteins. To identify secreted proteins potentially essential for virulence, the core secretome of A. fumigatus grown in minimal medium was determined. Two-dimensional gel electrophoretic separation and subsequent MALDI-TOF-MS/MS analyses resulted in the identification of 64 different proteins. Additionally, secretome analyses of A. fumigatus utilizing elastin, collagen or keratin as main carbon and nitrogen source were performed. Thereby, the alkaline serine protease Alp1 was identified as the most abundant protein and hence presumably represents an important protease during host infection. Interestingly, the Asp-hemolysin (Asp-HS), which belongs to the protein family of aegerolysins and which was often suggested to be involved in fungal virulence, was present in the secretome under all growth conditions tested. In addition, a second, non-secreted protein with an aegerolysin domain annotated as Asp-hemolysin-like (HS-like) protein can be found to be encoded in the genome of A. fumigatus. Generation and analysis of Asp-HS and HS-like deletion strains revealed no differences in phenotype compared to the corresponding wild-type strain. Furthermore, hemolysis and cytotoxicity was not altered in both single-deletion and double-deletion mutants lacking both aegerolysin genes. All mutant strains showed no attenuation in virulence in a mouse infection model for invasive pulmonary aspergillosis. Overall, this study provides a comprehensive

  4. Comorbid Analysis of Genes Associated with Autism Spectrum Disorders Reveals Differential Evolutionary Constraints

    Science.gov (United States)

    David, Maude M.; Enard, David; Ozturk, Alp; Daniels, Jena; Jung, Jae-Yoon; Diaz-Beltran, Leticia; Wall, Dennis. P.

    2016-01-01

    The burden of comorbidity in Autism Spectrum Disorder (ASD) is substantial. The symptoms of autism overlap with many other human conditions, reflecting common molecular pathologies suggesting that cross-disorder analysis will help prioritize autism gene candidates. Genes in the intersection between autism and related conditions may represent nonspecific indicators of dysregulation while genes unique to autism may play a more causal role. Thorough literature review allowed us to extract 125 ICD-9 codes comorbid to ASD that we mapped to 30 specific human disorders. In the present work, we performed an automated extraction of genes associated with ASD and its comorbid disorders, and found 1031 genes involved in ASD, among which 262 are involved in ASD only, with the remaining 779 involved in ASD and at least one comorbid disorder. A pathway analysis revealed 13 pathways not involved in any other comorbid disorders and therefore unique to ASD, all associated with basal cellular functions. These pathways differ from the pathways associated with both ASD and its comorbid conditions, with the latter being more specific to neural function. To determine whether the sequence of these genes have been subjected to differential evolutionary constraints, we studied long term constraints by looking into Genomic Evolutionary Rate Profiling, and showed that genes involved in several comorbid disorders seem to have undergone more purifying selection than the genes involved in ASD only. This result was corroborated by a higher dN/dS ratio for genes unique to ASD as compare to those that are shared between ASD and its comorbid disorders. Short-term evolutionary constraints showed the same trend as the pN/pS ratio indicates that genes unique to ASD were under significantly less evolutionary constraint than the genes associated with all other disorders. PMID:27414027

  5. Analysis of the full genome of human group C rotaviruses reveals lineage diversification and reassortment.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Fehér, Enikő; Marton, Szilvia; Calderaro, Adriana; Bányai, Krisztián

    2016-08-01

    Group C rotaviruses (RVC) are enteric pathogens of humans and animals. Whole-genome sequences are available only for few RVCs, leaving gaps in our knowledge about their genetic diversity. We determined the full-length genome sequence of two human RVCs (PR2593/2004 and PR713/2012), detected in Italy from hospital-based surveillance for rotavirus infection in 2004 and 2012. In the 11 RNA genomic segments, the two Italian RVCs segregated within separate intra-genotypic lineages showed variation ranging from 1.9 % (VP6) to 15.9 % (VP3) at the nucleotide level. Comprehensive analysis of human RVC sequences available in the databases allowed us to reveal the existence of at least two major genome configurations, defined as type I and type II. Human RVCs of type I were all associated with the M3 VP3 genotype, including the Italian strain PR2593/2004. Conversely, human RVCs of type II were all associated with the M2 VP3 genotype, including the Italian strain PR713/2012. Reassortant RVC strains between these major genome configurations were identified. Although only a few full-genome sequences of human RVCs, mostly of Asian origin, are available, the analysis of human RVC sequences retrieved from the databases indicates that at least two intra-genotypic RVC lineages circulate in European countries. Gathering more sequence data is necessary to develop a standardized genotype and intra-genotypic lineage classification system useful for epidemiological investigations and avoiding confusion in the literature.

  6. RNA-Seq analysis reveals a six-gene SoxR regulon in Streptomyces coelicolor.

    Directory of Open Access Journals (Sweden)

    Nawar Naseer

    Full Text Available The redox-regulated transcription factor SoxR is conserved in diverse bacteria, but emerging studies suggest that this protein plays distinct physiological roles in different bacteria. SoxR regulates a global oxidative stress response (involving > 100 genes against exogenous redox-cycling drugs in Escherichia coli and related enterics. In the antibiotic producers Streptomyces coelicolor and Pseudomonas aeruginosa, however, SoxR regulates a smaller number of genes that encode membrane transporters and proteins with homology to antibiotic-tailoring enzymes. In both S. coelicolor and P. aeruginosa, SoxR-regulated genes are expressed in stationary phase during the production of endogenously-produced redox-active antibiotics. These observations suggest that SoxR evolved to sense endogenous secondary metabolites and activate machinery to process and transport them in antibiotic-producing bacteria. Previous bioinformatics analysis that searched the genome for SoxR-binding sites in putative promoters defined a five-gene SoxR regulon in S. coelicolor including an ABC transporter, two oxidoreductases, a monooxygenase and an epimerase/dehydratase. Since this in silico screen may have missed potential SoxR-targets, we conducted a whole genome transcriptome comparison of wild type S. coelicolor and a soxR-deficient mutant in stationary phase using RNA-Seq. Our analysis revealed a sixth SoxR-regulated gene in S. coelicolor that encodes a putative quinone oxidoreductase. Knowledge of the full complement of genes regulated by SoxR will facilitate studies to elucidate the function of this regulatory molecule in antibiotic producers.

  7. RNA-Seq analysis reveals a six-gene SoxR regulon in Streptomyces coelicolor.

    Science.gov (United States)

    Naseer, Nawar; Shapiro, Joshua A; Chander, Monica

    2014-01-01

    The redox-regulated transcription factor SoxR is conserved in diverse bacteria, but emerging studies suggest that this protein plays distinct physiological roles in different bacteria. SoxR regulates a global oxidative stress response (involving > 100 genes) against exogenous redox-cycling drugs in Escherichia coli and related enterics. In the antibiotic producers Streptomyces coelicolor and Pseudomonas aeruginosa, however, SoxR regulates a smaller number of genes that encode membrane transporters and proteins with homology to antibiotic-tailoring enzymes. In both S. coelicolor and P. aeruginosa, SoxR-regulated genes are expressed in stationary phase during the production of endogenously-produced redox-active antibiotics. These observations suggest that SoxR evolved to sense endogenous secondary metabolites and activate machinery to process and transport them in antibiotic-producing bacteria. Previous bioinformatics analysis that searched the genome for SoxR-binding sites in putative promoters defined a five-gene SoxR regulon in S. coelicolor including an ABC transporter, two oxidoreductases, a monooxygenase and an epimerase/dehydratase. Since this in silico screen may have missed potential SoxR-targets, we conducted a whole genome transcriptome comparison of wild type S. coelicolor and a soxR-deficient mutant in stationary phase using RNA-Seq. Our analysis revealed a sixth SoxR-regulated gene in S. coelicolor that encodes a putative quinone oxidoreductase. Knowledge of the full complement of genes regulated by SoxR will facilitate studies to elucidate the function of this regulatory molecule in antibiotic producers. PMID:25162599

  8. Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high demand for thiamin transport and antioxidant protection.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Ketogulonicigenium vulgare, though grows poorly when mono-cultured, has been widely used in the industrial production of the precursor of vitamin C with the coculture of Bacillus megaterium. Various efforts have been made to clarify the synergic pattern of this artificial microbial community and to improve the growth and production ability of K. vulgare, but there is still no sound explanation. In previous research, we found that the addition of reduced glutathione into K. vulgare monoculture could significantly improve its growth and productivity. By performing SEM and TEM, we observed that after adding GSH into K. vulgare monoculture, cells became about 4-6 folds elongated, and formed intracytoplasmic membranes (ICM. To explore the molecular mechanism and provide insights into the investigation of the synergic pattern of the co-culture system, we conducted a comparative iTRAQ-2-D-LC-MS/MS-based proteomic analysis of K. vulgare grown under reduced glutathione. Principal component analysis of proteomic data showed that after the addition of glutathione, proteins for thiamin/thiamin pyrophosphate (TPP transport, glutathione transport and the maintenance of membrane integrity, together with several membrane-bound dehydrogenases had significant up-regulation. Besides, several proteins participating in the pentose phosphate pathway and tricarboxylic acid cycle were also up-regulated. Additionally, proteins combating intracellular reactive oxygen species were also up-regulated, which similarly occurred in K. vulgare when the co-cultured B. megaterium cells lysed from our former research results. This study reveals the demand for transmembrane transport of substrates, especially thiamin, and the demand for antioxidant protection of K. vulgare.

  9. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    Science.gov (United States)

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis.

  10. Comparative Genomic Analysis of Clinical and Environmental Vibrio Vulnificus Isolates Revealed Biotype 3 Evolutionary Relationships

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    Yael eKotton

    2015-01-01

    Full Text Available In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59% and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 kbp to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C and environmental (E, all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins were present in all human pathogenic strains (both biotype 3 and non-biotype 3 and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and

  11. Interspecies insertion polymorphism analysis reveals recent activity of transposable elements in extant coelacanths.

    Science.gov (United States)

    Naville, Magali; Chalopin, Domitille; Volff, Jean-Nicolas

    2014-01-01

    Coelacanths are lobe-finned fish represented by two extant species, Latimeria chalumnae in South Africa and Comoros and L. menadoensis in Indonesia. Due to their intermediate phylogenetic position between ray-finned fish and tetrapods in the vertebrate lineage, they are of great interest from an evolutionary point of view. In addition, extant specimens look similar to 300 million-year-old fossils; because of their apparent slowly evolving morphology, coelacanths have been often described as « living fossils ». As an underlying cause of such a morphological stasis, several authors have proposed a slow evolution of the coelacanth genome. Accordingly, sequencing of the L. chalumnae genome has revealed a globally low substitution rate for protein-coding regions compared to other vertebrates. However, genome and gene evolution can also be influenced by transposable elements, which form a major and dynamic part of vertebrate genomes through their ability to move, duplicate and recombine. In this work, we have searched for evidence of transposition activity in coelacanth genomes through the comparative analysis of orthologous genomic regions from both Latimeria species. Comparison of 5.7 Mb (0.2%) of the L. chalumnae genome with orthologous Bacterial Artificial Chromosome clones from L. menadoensis allowed the identification of 27 species-specific transposable element insertions, with a strong relative contribution of CR1 non-LTR retrotransposons. Species-specific homologous recombination between the long terminal repeats of a new coelacanth endogenous retrovirus was also detected. Our analysis suggests that transposon activity is responsible for at least 0.6% of genome divergence between both Latimeria species. Taken together, this study demonstrates that coelacanth genomes are not evolutionary inert: they contain recently active transposable elements, which have significantly contributed to post-speciation genome divergence in Latimeria.

  12. Interspecies insertion polymorphism analysis reveals recent activity of transposable elements in extant coelacanths.

    Directory of Open Access Journals (Sweden)

    Magali Naville

    Full Text Available Coelacanths are lobe-finned fish represented by two extant species, Latimeria chalumnae in South Africa and Comoros and L. menadoensis in Indonesia. Due to their intermediate phylogenetic position between ray-finned fish and tetrapods in the vertebrate lineage, they are of great interest from an evolutionary point of view. In addition, extant specimens look similar to 300 million-year-old fossils; because of their apparent slowly evolving morphology, coelacanths have been often described as « living fossils ». As an underlying cause of such a morphological stasis, several authors have proposed a slow evolution of the coelacanth genome. Accordingly, sequencing of the L. chalumnae genome has revealed a globally low substitution rate for protein-coding regions compared to other vertebrates. However, genome and gene evolution can also be influenced by transposable elements, which form a major and dynamic part of vertebrate genomes through their ability to move, duplicate and recombine. In this work, we have searched for evidence of transposition activity in coelacanth genomes through the comparative analysis of orthologous genomic regions from both Latimeria species. Comparison of 5.7 Mb (0.2% of the L. chalumnae genome with orthologous Bacterial Artificial Chromosome clones from L. menadoensis allowed the identification of 27 species-specific transposable element insertions, with a strong relative contribution of CR1 non-LTR retrotransposons. Species-specific homologous recombination between the long terminal repeats of a new coelacanth endogenous retrovirus was also detected. Our analysis suggests that transposon activity is responsible for at least 0.6% of genome divergence between both Latimeria species. Taken together, this study demonstrates that coelacanth genomes are not evolutionary inert: they contain recently active transposable elements, which have significantly contributed to post-speciation genome divergence in Latimeria.

  13. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    Energy Technology Data Exchange (ETDEWEB)

    Chong, S.S.; McCall, A.E.; Cota, J. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  14. Molecular systematic analysis reveals cryptic tertiary diversification of a widespread tropical rain forest tree.

    Science.gov (United States)

    Dick, Christopher W; Abdul-Salim, Kobinah; Bermingham, Eldredge

    2003-12-01

    The broad geographic range of many Neotropical rain forest tree species implies excellent dispersal abilities or range establishment that preceded the formation of current dispersal barriers. In order to initiate historical analyses of such widespread Neotropical trees, we sequenced the nuclear ribosomal spacer (ITS) region of Symphonia globulifera L. f. (Clusiaceae) from populations spanning the Neotropics and western Africa. This rain forest tree has left unmistakable Miocene fossils in Mesoamerica (15.5-18.2 Ma) and in South America ( approximately 15 Ma). Although marine dispersal of S. globulifera is considered improbable, our study establishes three marine dispersal events leading to the colonization of Mesoamerica, the Amazon basin, and the West Indies, thus supporting the paleontological data. Our phylogeographic analysis revealed the spatial extent of the three Neotropical S. globulifera clades, which represent trans-Andes (Mesoamerica+west Ecuador), cis-Andes (Amazonia+Guiana), and the West Indies. Strong phylogeographic structure found among trans-Andean populations of S. globulifera stands in contrast to an absence of ITS nucleotide variation across the Amazon basin and indicates profound regional differences in the demographic history of this rain forest tree. Drawing from these results, we provide a historical biogeographic hypothesis to account for differences in the patterns of beta diversity within Mesoamerican and Amazonian forests. PMID:14737707

  15. GC--MS analysis reveals production of 2--Phenylethanol from Aspergillus niger endophytic in rose.

    Science.gov (United States)

    Wani, Masood Ahmed; Sanjana, Kaul; Kumar, Dhar Manoj; Lal, Dhar Kanahya

    2010-02-01

    Endophytes include all organisms that during a variable period of their life, colonize the living internal tissues of their hosts without causing detectable symptoms. Several fungal endophytes have been isolated from a variety of plant species which have proved themselves as a rich source of secondary metabolites. The reported natural products from endophytes include antibiotics, immunosuppresants, anticancer compounds, antioxidant agents, etc. For the first time Rosa damacaena (rose) has been explored for its endophytes. The rose oil industry is the major identified deligence for its application in perfumery, flavouring, ointments, and pharmaceuticals including various herbal products. During the present investigation fungal endophytes were isolated from Rosa damacaena. A total of fifty four isolates were isolated out of which sixteen isolates were screened for the production of secondary metabolites. GCMS analysis reveals the production of 2-phenylethanol by one of the isolates JUBT 3M which was identified as Aspergillus niger. This is the first report of production of 2-phenylethanol from endophytic A. niger. 2-phenylethanol is an important constituent of rose oil constituting about 4.06% of rose oil. Presence of 2-phenylethanol indicates that the endophyte of rose may duplicate the biosynthesis of phenyl propanoids by rose plant. Besides this, the other commercial applications of phenylethanol include its use in antiseptics, disinfectants, anti-microbials and preservative in pharmaceuticals. PMID:20082377

  16. Mosaic Analysis with Double Markers Reveals Cell-Type-Specific Paternal Growth Dominance

    Directory of Open Access Journals (Sweden)

    Simon Hippenmeyer

    2013-03-01

    Full Text Available Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM in mice to create uniparental disomies (UPDs and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2, accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.

  17. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    Science.gov (United States)

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis. PMID:19663508

  18. Gamma-Tocotrienol Modulated Gene Expression in Senescent Human Diploid Fibroblasts as Revealed by Microarray Analysis

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    Suzana Makpol

    2013-01-01

    Full Text Available The effect of γ-tocotrienol, a vitamin E isomer, in modulating gene expression in cellular aging of human diploid fibroblasts was studied. Senescent cells at passage 30 were incubated with 70 μM of γ-tocotrienol for 24 h. Gene expression patterns were evaluated using Sentrix HumanRef-8 Expression BeadChip from Illumina, analysed using GeneSpring GX10 software, and validated using quantitative RT-PCR. A total of 100 genes were differentially expressed (P<0.001 by at least 1.5 fold in response to γ-tocotrienol treatment. Amongst the genes were IRAK3, SelS, HSPA5, HERPUD1, DNAJB9, SEPR1, C18orf55, ARF4, RINT1, NXT1, CADPS2, COG6, and GLRX5. Significant gene list was further analysed by Gene Set Enrichment Analysis (GSEA, and the Normalized Enrichment Score (NES showed that biological processes such as inflammation, protein transport, apoptosis, and cell redox homeostasis were modulated in senescent fibroblasts treated with γ-tocotrienol. These findings revealed that γ-tocotrienol may prevent cellular aging of human diploid fibroblasts by modulating gene expression.

  19. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  20. Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

    Science.gov (United States)

    Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

    2016-01-01

    Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

  1. Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population.

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    Roberto Rosini

    Full Text Available The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl transferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

  2. Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population.

    Science.gov (United States)

    Rosini, Roberto; Campisi, Edmondo; De Chiara, Matteo; Tettelin, Hervé; Rinaudo, Daniela; Toniolo, Chiara; Metruccio, Matteo; Guidotti, Silvia; Sørensen, Uffe B Skov; Kilian, Mogens; Ramirez, Mario; Janulczyk, Robert; Donati, Claudio; Grandi, Guido; Margarit, Immaculada

    2015-01-01

    The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl transferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

  3. Metatranscriptome analysis reveals host-microbiome interactions in traps of carnivorous Genlisea species

    Directory of Open Access Journals (Sweden)

    Hieu X. Cao

    2015-07-01

    Full Text Available In the carnivorous plant genus Genlisea a unique lobster pot trapping mechanism supplements nutrition in nutrient-poor habitats. A wide spectrum of microbes frequently occurs in Genlisea’s leaf-derived traps without clear relevance for Genlisea carnivory. We sequenced the metatranscriptomes of subterrestrial traps versus the aerial chlorophyll-containing leaves of G. nigrocaulis and of G. hispidula. Ribosomal RNA assignment revealed soil-borne microbial diversity in Genlisea traps, with 92 genera of 19 phyla present in more than one sample. Microbes from 16 of these phyla including proteobacteria, green algae, amoebozoa, fungi, ciliates and metazoans, contributed additionally short-lived mRNA to the metatranscriptome. Furthermore, transcripts of 438 members of hydrolases (e.g. proteases, phosphatases, lipases, mainly resembling those of metazoans, ciliates and green algae, were found. Compared to aerial leaves, Genlisea traps displayed a transcriptional up-regulation of endogenous NADH oxidases generating reactive oxygen species as well as of acid phosphatases for prey digestion. A leaf-versus-trap transcriptome comparison reflects that carnivory provides inorganic P- and different forms of N-compounds (ammonium, nitrate, amino acid, oligopeptides and implies the need to protect trap cells against oxidative stress. The analysis elucidates a complex food web inside the Genlisea traps, and suggests ecological relationships between this plant genus and its entrapped microbiome.

  4. Metatranscriptome analysis reveals host-microbiome interactions in traps of carnivorous Genlisea species.

    Science.gov (United States)

    Cao, Hieu X; Schmutzer, Thomas; Scholz, Uwe; Pecinka, Ales; Schubert, Ingo; Vu, Giang T H

    2015-01-01

    In the carnivorous plant genus Genlisea a unique lobster pot trapping mechanism supplements nutrition in nutrient-poor habitats. A wide spectrum of microbes frequently occurs in Genlisea's leaf-derived traps without clear relevance for Genlisea carnivory. We sequenced the metatranscriptomes of subterrestrial traps vs. the aerial chlorophyll-containing leaves of G. nigrocaulis and of G. hispidula. Ribosomal RNA assignment revealed soil-borne microbial diversity in Genlisea traps, with 92 genera of 19 phyla present in more than one sample. Microbes from 16 of these phyla including proteobacteria, green algae, amoebozoa, fungi, ciliates and metazoans, contributed additionally short-lived mRNA to the metatranscriptome. Furthermore, transcripts of 438 members of hydrolases (e.g., proteases, phosphatases, lipases), mainly resembling those of metazoans, ciliates and green algae, were found. Compared to aerial leaves, Genlisea traps displayed a transcriptional up-regulation of endogenous NADH oxidases generating reactive oxygen species as well as of acid phosphatases for prey digestion. A leaf-vs.-trap transcriptome comparison reflects that carnivory provides inorganic P- and different forms of N-compounds (ammonium, nitrate, amino acid, oligopeptides) and implies the need to protect trap cells against oxidative stress. The analysis elucidates a complex food web inside the Genlisea traps, and suggests ecological relationships between this plant genus and its entrapped microbiome. PMID:26236284

  5. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

    Science.gov (United States)

    Jiang, Lulu; Hindmarch, Charles C. T.; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W.; Welsh, Gavin I.

    2016-01-01

    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes. PMID:27774996

  6. Global analysis of transcriptionally engaged yeast RNA polymerase III reveals extended tRNA transcripts.

    Science.gov (United States)

    Turowski, Tomasz W; Leśniewska, Ewa; Delan-Forino, Clementine; Sayou, Camille; Boguta, Magdalena; Tollervey, David

    2016-07-01

    RNA polymerase III (RNAPIII) synthesizes a range of highly abundant small stable RNAs, principally pre-tRNAs. Here we report the genome-wide analysis of nascent transcripts attached to RNAPIII under permissive and restrictive growth conditions. This revealed strikingly uneven polymerase distributions across transcription units, generally with a predominant 5' peak. This peak was higher for more heavily transcribed genes, suggesting that initiation site clearance is rate-limiting during RNAPIII transcription. Down-regulation of RNAPIII transcription under stress conditions was found to be uneven; a subset of tRNA genes showed low response to nutrient shift or loss of the major transcription regulator Maf1, suggesting potential "housekeeping" roles. Many tRNA genes were found to generate long, 3'-extended forms due to read-through of the canonical poly(U) terminators. The degree of read-through was anti-correlated with the density of U-residues in the nascent tRNA, and multiple, functional terminators can be located far downstream. The steady-state levels of 3'-extended pre-tRNA transcripts are low, apparently due to targeting by the nuclear surveillance machinery, especially the RNA binding protein Nab2, cofactors for the nuclear exosome, and the 5'-exonuclease Rat1. PMID:27206856

  7. Gene coexpression analysis reveals complex metabolism of the monoterpene alcohol linalool in Arabidopsis flowers.

    Science.gov (United States)

    Ginglinger, Jean-François; Boachon, Benoit; Höfer, René; Paetz, Christian; Köllner, Tobias G; Miesch, Laurence; Lugan, Raphael; Baltenweck, Raymonde; Mutterer, Jérôme; Ullmann, Pascaline; Beran, Franziska; Claudel, Patricia; Verstappen, Francel; Fischer, Marc J C; Karst, Francis; Bouwmeester, Harro; Miesch, Michel; Schneider, Bernd; Gershenzon, Jonathan; Ehlting, Jürgen; Werck-Reichhart, Danièle

    2013-11-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus predicted to be involved in monoterpenoid metabolism. We show that all four selected genes, the two terpene synthases (TPS10 and TPS14) and the two cytochrome P450s (CYP71B31 and CYP76C3), are simultaneously expressed at anthesis, mainly in upper anther filaments and in petals. Upon transient expression in Nicotiana benthamiana, the TPS enzymes colocalize in vesicular structures associated with the plastid surface, whereas the P450 proteins were detected in the endoplasmic reticulum. Whether they were expressed in Saccharomyces cerevisiae or in N. benthamiana, the TPS enzymes formed two different enantiomers of linalool: (-)-(R)-linalool for TPS10 and (+)-(S)-linalool for TPS14. Both P450 enzymes metabolize the two linalool enantiomers to form different but overlapping sets of hydroxylated or epoxidized products. These oxygenated products are not emitted into the floral headspace, but accumulate in floral tissues as further converted or conjugated metabolites. This work reveals complex linalool metabolism in Arabidopsis flowers, the ecological role of which remains to be determined.

  8. Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis.

    Science.gov (United States)

    Caulin, Aleah F; Graham, Trevor A; Wang, Li-San; Maley, Carlo C

    2015-07-19

    Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans. PMID:26056366

  9. Genome-wide analysis reveals specificities of Cpf1 endonucleases in human cells.

    Science.gov (United States)

    Kim, Daesik; Kim, Jungeun; Hur, Junho K; Been, Kyung Wook; Yoon, Sun-Heui; Kim, Jin-Soo

    2016-08-01

    Programmable clustered regularly interspaced short palindromic repeats (CRISPR) Cpf1 endonucleases are single-RNA-guided (crRNA) enzymes that recognize thymidine-rich protospacer-adjacent motif (PAM) sequences and produce cohesive double-stranded breaks (DSBs). Genome editing with CRISPR-Cpf1 endonucleases could provide an alternative to CRISPR-Cas9 endonucleases, but the determinants of targeting specificity are not well understood. Using mismatched crRNAs we found that Cpf1 could tolerate single or double mismatches in the 3' PAM-distal region, but not in the 5' PAM-proximal region. Genome-wide analysis of cleavage sites in vitro for eight Cpf1 nucleases using Digenome-seq revealed that there were 6 (LbCpf1) and 12 (AsCpf1) cleavage sites per crRNA in the human genome, fewer than are present for Cas9 nucleases (>90). Most Cpf1 off-target cleavage sites did not produce mutations in cells. We found mismatches in either the 3' PAM-distal region or in the PAM sequence of 12 off-target sites that were validated in vivo. Off-target effects were completely abrogated by using preassembled, recombinant Cpf1 ribonucleoproteins.

  10. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies. PMID:26758200

  11. Temporal proteomic analysis reveals continuous impairment of intestinal development in neonatal piglets with intrauterine growth restriction.

    Science.gov (United States)

    Wang, Xiaoqiu; Wu, Weizong; Lin, Gang; Li, Defa; Wu, Guoyao; Wang, Junjun

    2010-02-01

    Efficiency of nutrient utilization is reduced in neonates with intrauterine growth restriction (IUGR) compared with those with a normal birth weight (NBW). However, the underlying mechanisms are largely unknown. In this study, we applied temporal proteomic approach, coupled with histological and biochemical analyses, to study dynamic changes of the proteome in the small intestinal mucosa of IUGR piglets during the nursing period (Days 1, 7 and 21). We identified 56 differentially expressed protein spots between IUGR and NBW piglets. These proteins participate in key biological processes, including (1) absorption, digestion and transport of nutrients; (2) cell structure and motility; (3) glucose and energy metabolism; (4) lipid metabolism; (5) amino acid metabolism; (6) mineral and vitamin metabolism; (7) cellular redox homeostasis; (8) stress response; and (9) apoptosis. The results of our temporal proteomics analysis reveal continuous impairment of intestinal development in neonatal piglets with IUGR. The findings have important implications for understanding metabolic defects in the small intestine of IUGR neonates and are expected to provide new strategies to improve their survival and growth.

  12. Retrospective stable isotope analysis reveals ecosystem responses to river regulation over the last century.

    Science.gov (United States)

    Turner, Thomas F; Krabbenhoft, Trevor I; Collyer, Michael L; Krabbenhoft, Corey A; Edwards, Melanie S; Sharp, Zachary D

    2015-12-01

    Disruption of natural flow regimes, nutrient pollution, and other consequences of human population growth and development have impacted most major rivers of the world. Alarming losses of aquatic biodiversity coincide with human-caused river alteration, but effects of biotic homogenization on aquatic ecosystem processes are not as well documented. This is because unaltered systems for comparison are scarce, and some ecosystem-wide effects may take decades to manifest. We evaluated aquatic ecosystem responses to extensive river- floodplain engineering and nutrient addition in the Rio Grande of southwestern North America as revealed by changes in trophic structure of, and resource availability to, the fish community. Stable Isotope Analysis (SIA) was conducted on museum-preserved fishes collected over a 70-year period of intensive river management and exponential human population growth. Trophic complexity and resource heterogeneity for fish consumers (measured as "isotopic niche breadth") decreased following sediment deprivation and channelization, and these effects persist into the present. Increased nutrient inputs led to δ15N enrichment in the entire fish community at all affected sites, and a shift to autochthonous sources of carbon at the most proximal site downstream of wastewater release, probably via bottom-up transfer. Overall, retrospective SIA of apex consumers suggests radical change and functional impairment of a floodplain river ecosystem already marked by significant biodiversity loss.

  13. The complement system of elasmobranches revealed by liver transcriptome analysis of a hammerhead shark, Sphyrna zygaena.

    Science.gov (United States)

    Goshima, Masayuki; Sekiguchi, Reo; Matsushita, Misao; Nonaka, Masaru

    2016-08-01

    Comprehensive studies of the complement genes in basal vertebrates have revealed that cyclostomes have apparently primitive complement systems whereas bony fish have well-developed complement systems comparable to those of mammals. Here we have performed liver transcriptome analysis of a hammerhead shark, Sphyrna zygaeana, to elucidate the early history of vertebrate complement evolution. Identified genes were; one C1qB, one C1r, one C1s, one MASP-1/-3, one MASP-2, two factor B/C2, one C3, three C4, one C5, one C6, one C7, one C8A, three C8B, one C8G, one C9, two factor I and one S protein. No MBL, ficolin, C1qA or C1qC were found. These results indicate that the lectin, classical, alternative and lytic pathways were established in the common ancestor of jawed vertebrates. In addition to the absence of MBL and ficolin, the MASP transcripts lacked the serine protease domain, suggesting that the lectin pathway was lost in the hammerhead shark lineage. PMID:26987526

  14. Genome-Wide Analysis Revealed the Complex Regulatory Network of Brassinosteroid Effects in Photomorphogenesis

    Institute of Scientific and Technical Information of China (English)

    Li Song; Xiao-Yi Zhou; Li Li; Liang-Jiao Xue; Xi Yang; Hong-Wei Xue

    2009-01-01

    Light and brassinosteroids (BRs) have been proved to be crucial in regulating plant growth and development;however,the mechanism of how they synergistically function is still largely unknown.To explore the underlying mechanisms in photomorphogenesis,genome-wide analyses were carried out through examining the gene expressions of the dark-grown WT or BR biosynthesis-defective mutant det2 seedlings in the presence of light stimuli or exogenous Brassinolide (BL).Results showed that BR deficiency stimulates,while BL treatment suppresses,the expressions of lightresponsive genes and photomorphogenesis,confirming the negative effects of BR in photomorphogenesis.This is consistent with the specific effects of BR on the expression of genes involved in cell wall modification,cellular metabolism and energy utilization during dark-light transition.Further analysis revealed that hormone biosynthesis and signaling-related genes,especially those of auxin,were altered under BL treatment or light stimuli,indicating that BR may modulate photomorphogenesis through synergetic regulation with other hormones.Additionally,suppressed ubiquitin-cycle pathway during light-dark transition hinted the presence of a complicated network among light,hormone,and protein degradation.The study provides the direct evidence of BR effects in photomorphogenesis and identified the genes involved in BR and light signaling pathway,which will help to elucidate the molecular mechanism of plant photomorphogenesis.

  15. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs. PMID:26985781

  16. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  17. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

    Directory of Open Access Journals (Sweden)

    Tang Vivian W

    2006-12-01

    Full Text Available Abstract Background Zonula occludens, also known as the tight junction, is a specialized cell-cell interaction characterized by membrane "kisses" between epithelial cells. A cytoplasmic plaque of ~100 nm corresponding to a meshwork of densely packed proteins underlies the tight junction membrane domain. Due to its enormous size and difficulties in obtaining a biochemically pure fraction, the molecular composition of the tight junction remains largely unknown. Results A novel biochemical purification protocol has been developed to isolate tight junction protein complexes from cultured human epithelial cells. After identification of proteins by mass spectroscopy and fingerprint analysis, candidate proteins are scored and assessed individually. A simple algorithm has been devised to incorporate transmembrane domains and protein modification sites for scoring membrane proteins. Using this new scoring system, a total of 912 proteins have been identified. These 912 hits are analyzed using a bioinformatics approach to bin the hits in 4 categories: configuration, molecular function, cellular function, and specialized process. Prominent clusters of proteins related to the cytoskeleton, cell adhesion, and vesicular traffic have been identified. Weaker clusters of proteins associated with cell growth, cell migration, translation, and transcription are also found. However, the strongest clusters belong to synaptic proteins and signaling molecules. Localization studies of key components of synaptic transmission have confirmed the presence of both presynaptic and postsynaptic proteins at the tight junction domain. To correlate proteomics data with structure, the tight junction has been examined using electron microscopy. This has revealed many novel structures including end-on cytoskeletal attachments, vesicles fusing/budding at the tight junction membrane domain, secreted substances encased between the tight junction kisses, endocytosis of tight junction

  18. Diversity in a Polymicrobial Community Revealed by Analysis of Viromes, Endolysins and CRISPR Spacers

    Science.gov (United States)

    Treangen, Todd J.; Koren, Sergey; Pop, Mihai; Bhaya, Devaki

    2016-01-01

    The polymicrobial biofilm communities in Mushroom and Octopus Spring in Yellowstone National Park (YNP) are well characterized, yet little is known about the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2–13), Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1, contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage predators. To analyze phage populations from Octopus Spring biofilms, we sequenced a viral enriched fraction. To assemble and analyze phage metagenomic data, we developed a custom module, VIRITAS, implemented within the MetAMOS framework. This module bins contigs into groups based on tetranucleotide frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this pipeline we were able to assemble phage sequences into contigs and bin them into three clusters that corroborated with their potential host range. The virome contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a recognizable Pfam domain while the rest were hypothetical. Of the recognized domains with CRISPR spacer matches, was the phage endolysin used by lytic phage to disrupt cells. Analysis of the endolysins present in the thermophilic cyanophage contigs revealed a subset of characterized endolysins as well as a Glyco_hydro_108 (PF05838) domain not previously associated with sequenced cyanophages. A search for CRISPR spacer matches to all identified phage endolysins demonstrated that a majority of endolysin domains were targets. This strategy provides a general way to link host and phage as endolysins are known to be widely distributed in bacteriophage. Endolysins can also provide information about host cell wall composition and have the additional potential to be used as targets for novel therapeutics. PMID:27611571

  19. Multivariate pattern analysis reveals anatomical connectivity differences between the left and right mesial temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Peng Fang

    2015-01-01

    Full Text Available Previous studies have demonstrated differences of clinical signs and functional brain network organizations between the left and right mesial temporal lobe epilepsy (mTLE, but the anatomical connectivity differences underlying functional variance between the left and right mTLE remain uncharacterized. We examined 43 (22 left, 21 right mTLE patients with hippocampal sclerosis and 39 healthy controls using diffusion tensor imaging. After the whole-brain anatomical networks were constructed for each subject, multivariate pattern analysis was applied to classify the left mTLE from the right mTLE and extract the anatomical connectivity differences between the left and right mTLE patients. The classification results reveal 93.0% accuracy for the left mTLE versus the right mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited a different connectivity pattern in the cortical-limbic network and cerebellum. The majority of the most discriminating anatomical connections were located within or across the cortical-limbic network and cerebellum, thereby indicating that these disease-related anatomical network alterations may give rise to a portion of the complex of emotional and memory deficit between the left and right mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and parahippocampal gyrus, which exhibit high discriminative power in classification, may play critical roles in the pathophysiology of mTLE. The current study demonstrated that anatomical connectivity differences between the left mTLE and the right mTLE may have the potential to serve as a neuroimaging biomarker to guide personalized diagnosis of the left and right mTLE.

  20. Transcriptomic analysis of the oleaginous microalga Neochloris oleoabundans reveals metabolic insights into triacylglyceride accumulation

    Directory of Open Access Journals (Sweden)

    Rismani-Yazdi Hamid

    2012-09-01

    Full Text Available Abstract Background The lack of sequenced genomes for oleaginous microalgae limits our understanding of the mechanisms these organisms utilize to become enriched in triglycerides. Here we report the de novo transcriptome assembly and quantitative gene expression analysis of the oleaginous microalga Neochloris oleoabundans, with a focus on the complex interaction of pathways associated with the production of the triacylglycerol (TAG biofuel precursor. Results After growth under nitrogen replete and nitrogen limiting conditions, we quantified the cellular content of major biomolecules including total lipids, triacylglycerides, starch, protein, and chlorophyll. Transcribed genes were sequenced, the transcriptome was assembled de novo, and the expression of major functional categories, relevant pathways, and important genes was quantified through the mapping of reads to the transcriptome. Over 87 million, 77 base pair high quality reads were produced on the Illumina HiSeq sequencing platform. Metabolite measurements supported by genes and pathway expression results indicated that under the nitrogen-limiting condition, carbon is partitioned toward triglyceride production, which increased fivefold over the nitrogen-replete control. In addition to the observed overexpression of the fatty acid synthesis pathway, TAG production during nitrogen limitation was bolstered by repression of the β-oxidation pathway, up-regulation of genes encoding for the pyruvate dehydrogenase complex which funnels acetyl-CoA to lipid biosynthesis, activation of the pentose phosphate pathway to supply reducing equivalents to inorganic nitrogen assimilation and fatty acid biosynthesis, and the up-regulation of lipases—presumably to reconstruct cell membranes in order to supply additional fatty acids for TAG biosynthesis. Conclusions Our quantitative transcriptome study reveals a broad overview of how nitrogen stress results in excess TAG production in N. oleoabundans, and

  1. Computational bacterial genome-wide analysis of phylogenetic profiles reveals potential virulence genes of Streptococcus agalactiae.

    Directory of Open Access Journals (Sweden)

    Frank Po-Yen Lin

    Full Text Available The phylogenetic profile of a gene is a reflection of its evolutionary history and can be defined as the differential presence or absence of a gene in a set of reference genomes. It has been employed to facilitate the prediction of gene functions. However, the hypothesis that the application of this concept can also facilitate the discovery of bacterial virulence factors has not been fully examined. In this paper, we test this hypothesis and report a computational pipeline designed to identify previously unknown bacterial virulence genes using group B streptococcus (GBS as an example. Phylogenetic profiles of all GBS genes across 467 bacterial reference genomes were determined by candidate-against-all BLAST searches,which were then used to identify candidate virulence genes by machine learning models. Evaluation experiments with known GBS virulence genes suggested good functional and model consistency in cross-validation analyses (areas under ROC curve, 0.80 and 0.98 respectively. Inspection of the top-10 genes in each of the 15 virulence functional groups revealed at least 15 (of 119 homologous genes implicated in virulence in other human pathogens but previously unrecognized as potential virulence genes in GBS. Among these highly-ranked genes, many encode hypothetical proteins with possible roles in GBS virulence. Thus, our approach has led to the identification of a set of genes potentially affecting the virulence potential of GBS, which are potential candidates for further in vitro and in vivo investigations. This computational pipeline can also be extended to in silico analysis of virulence determinants of other bacterial pathogens.

  2. An evolutionary analysis of flightin reveals a conserved motif unique and widespread in Pancrustacea.

    Science.gov (United States)

    Soto-Adames, Felipe N; Alvarez-Ortiz, Pedro; Vigoreaux, Jim O

    2014-01-01

    Flightin is a thick filament protein that in Drosophila melanogaster is uniquely expressed in the asynchronous, indirect flight muscles (IFM). Flightin is required for the structure and function of the IFM and is indispensable for flight in Drosophila. Given the importance of flight acquisition in the evolutionary history of insects, here we study the phylogeny and distribution of flightin. Flightin was identified in 69 species of hexapods in classes Collembola (springtails), Protura, Diplura, and insect orders Thysanura (silverfish), Dictyoptera (roaches), Orthoptera (grasshoppers), Pthiraptera (lice), Hemiptera (true bugs), Coleoptera (beetles), Neuroptera (green lacewing), Hymenoptera (bees, ants, and wasps), Lepidoptera (moths), and Diptera (flies and mosquitoes). Flightin was also found in 14 species of crustaceans in orders Anostraca (water flea), Cladocera (brine shrimp), Isopoda (pill bugs), Amphipoda (scuds, sideswimmers), and Decapoda (lobsters, crabs, and shrimps). Flightin was not identified in representatives of chelicerates, myriapods, or any species outside Pancrustacea (Tetraconata, sensu Dohle). Alignment of amino acid sequences revealed a conserved region of 52 amino acids, referred herein as WYR, that is bound by strictly conserved tryptophan (W) and arginine (R) and an intervening sequence with a high content of tyrosines (Y). This motif has no homologs in GenBank or PROSITE and is unique to flightin and paraflightin, a putative flightin paralog identified in decapods. A third motif of unclear affinities to pancrustacean WYR was observed in chelicerates. Phylogenetic analysis of amino acid sequences of the conserved motif suggests that paraflightin originated before the divergence of amphipods, isopods, and decapods. We conclude that flightin originated de novo in the ancestor of Pancrustacea > 500 MYA, well before the divergence of insects (~400 MYA) and the origin of flight (~325 MYA), and that its IFM-specific function in Drosophila is a more

  3. Diversity in a Polymicrobial Community Revealed by Analysis of Viromes, Endolysins and CRISPR Spacers.

    Science.gov (United States)

    Davison, Michelle; Treangen, Todd J; Koren, Sergey; Pop, Mihai; Bhaya, Devaki

    2016-01-01

    The polymicrobial biofilm communities in Mushroom and Octopus Spring in Yellowstone National Park (YNP) are well characterized, yet little is known about the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2-13), Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1, contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage predators. To analyze phage populations from Octopus Spring biofilms, we sequenced a viral enriched fraction. To assemble and analyze phage metagenomic data, we developed a custom module, VIRITAS, implemented within the MetAMOS framework. This module bins contigs into groups based on tetranucleotide frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this pipeline we were able to assemble phage sequences into contigs and bin them into three clusters that corroborated with their potential host range. The virome contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a recognizable Pfam domain while the rest were hypothetical. Of the recognized domains with CRISPR spacer matches, was the phage endolysin used by lytic phage to disrupt cells. Analysis of the endolysins present in the thermophilic cyanophage contigs revealed a subset of characterized endolysins as well as a Glyco_hydro_108 (PF05838) domain not previously associated with sequenced cyanophages. A search for CRISPR spacer matches to all identified phage endolysins demonstrated that a majority of endolysin domains were targets. This strategy provides a general way to link host and phage as endolysins are known to be widely distributed in bacteriophage. Endolysins can also provide information about host cell wall composition and have the additional potential to be used as targets for novel therapeutics. PMID:27611571

  4. Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Denisa Liszeková

    Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

  5. Analysis of newly established EST databases reveals similarities between heart regeneration in newt and fish

    Directory of Open Access Journals (Sweden)

    Weis Patrick

    2010-01-01

    Full Text Available Abstract Background The newt Notophthalmus viridescens possesses the remarkable ability to respond to cardiac damage by formation of new myocardial tissue. Surprisingly little is known about changes in gene activities that occur during the course of regeneration. To begin to decipher the molecular processes, that underlie restoration of functional cardiac tissue, we generated an EST database from regenerating newt hearts and compared the transcriptional profile of selected candidates with genes deregulated during zebrafish heart regeneration. Results A cDNA library of 100,000 cDNA clones was generated from newt hearts 14 days after ventricular injury. Sequencing of 11520 cDNA clones resulted in 2894 assembled contigs. BLAST searches revealed 1695 sequences with potential homology to sequences from the NCBI database. BLAST searches to TrEMBL and Swiss-Prot databases assigned 1116 proteins to Gene Ontology terms. We also identified a relatively large set of 174 ORFs, which are likely to be unique for urodele amphibians. Expression analysis of newt-zebrafish homologues confirmed the deregulation of selected genes during heart regeneration. Sequences, BLAST results and GO annotations were visualized in a relational web based database followed by grouping of identified proteins into clusters of GO Terms. Comparison of data from regenerating zebrafish hearts identified biological processes, which were uniformly overrepresented during cardiac regeneration in newt and zebrafish. Conclusion We concluded that heart regeneration in newts and zebrafish led to the activation of similar sets of genes, which suggests that heart regeneration in both species might follow similar principles. The design of the newly established newt EST database allows identification of molecular pathways important for heart regeneration.

  6. Particle Motion Analysis Reveals Nanoscale Bond Characteristics and Enhances Dynamic Range for Biosensing.

    Science.gov (United States)

    Visser, Emiel W A; van IJzendoorn, Leo J; Prins, Menno W J

    2016-03-22

    Biofunctionalized colloidal particles are widely used as labels in bioanalytical assays, lab-on-chip devices, biophysical research, and in studies on live biological systems. With detection resolution going down to the level of single particles and single molecules, understanding the nature of the interaction of the particles with surfaces and substrates becomes of paramount importance. Here, we present a comprehensive study of motion patterns of colloidal particles maintained in close proximity to a substrate by short molecular tethers (40 nm). The motion of the particles (500-1000 nm) was optically tracked with a very high localization accuracy (below 3 nm). A surprisingly large variation in motion patterns was observed, which can be attributed to properties of the particle-molecule-substrate system, namely the bond number, the nature of the bond, particle protrusions, and substrate nonuniformities. Experimentally observed motion patterns were compared to numerical Monte Carlo simulations, revealing a close correspondence between the observed motion patterns and properties of the molecular system. Particles bound via single tethers show distinct disc-, ring-, and bell-shaped motion patterns, where the ring- and bell-shaped patterns are caused by protrusions on the particle in the direct vicinity of the molecular attachment point. Double and triple tethered particles exhibit stripe-shaped and triangular-shaped motion patterns, respectively. The developed motion pattern analysis allows for discrimination between particles bound by different bond types, which opens the possibility to improve the limit of detection and the dynamic range of bioanalytical assays, with a projected increase of dynamic range by nearly 2 orders of magnitude.

  7. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  8. Sr Isotope Analysis of Lacustrine Fossils Reveals Paleohydrological Reorganisation in the Turkana Basin Through the Holocene.

    Science.gov (United States)

    Vonhof, H.; Lubbe, J. V. D.; Joordens, J. J.; Feibel, C. S.; Junginger, A.; Garcin, Y.; Krause-Nehring, J.; Beck, C.; Johnson, T. C.

    2015-12-01

    Lake Turkana in northern Kenya is one of the largest lakes in the East African Rift System (EARS) that experienced significant climate-driven lake level variation over the Holocene. Arguably the most important feature of Holocene climate change in the EARS is the termination of the African Humid Period (AHP), that caused a ~70 meter lake level drop in Lake Turkana. The precise hydrological response to the termination of the AHP is potentially complex, because Lake Turkana lies at the cross roads of two large atmospheric convection systems; the Intertropical Convergence Zone (ITCZ) and the Congo Air Boundary (CAB). Shifting of these atmospheric systems around the end of the AHP dramatically rearranged spatial rainfall patterns in the Turkana Basin catchment, causing changes in relative runoff contributions from the different sub-catchments in the Turkana Basin. We here present a Holocene Turkana lake water Sr-isotope reconstruction, based on the analysis of well-dated lacustrine ostracods and shells. This reconstruction reveals consistently high Sr isotope values for the early Holocene, followed by a remarkable drop of Sr isotope ratios around the AHP termination. We interpret this pattern to represent a westward shift in the location of the CAB, leading to the reduction and eventual shutdown of runoff contribution from the Chew Bahir Basin to the Turkana Basin at the end of the AHP. The record demonstrates the exceptional suitability of Sr isotope data for this type of paleohydrological reconstructions. This is mainly due to the chemically conservative Sr-isotope mass balance in EARS lake systems, which is insensitive to environmental change at seasonal timescales that so often overprints the longer term climate signal in stable (oxygen and carbon) isotope records of these lakes. Furthermore, when Sr-isotope signatures of the contributing sub-catchments are known, the observed Sr isotope trends can be interpreted in terms of spatial shifts in climate driven runoff

  9. Proteomic analysis reveals metabolic and regulatory systems involved the syntrophic and axenic lifestyle of Syntrophomonas wolfei.

    Directory of Open Access Journals (Sweden)

    Jessica Rhea Sieber

    2015-02-01

    Full Text Available Microbial syntrophy is a vital metabolic interaction necessary for the complete oxidation of organic biomass to methane in all-anaerobic ecosystems. However, this process is thermodynamically constrained and represents an ecosystem-level metabolic bottleneck. To gain insight into the physiology of this process, a shotgun proteomic approach was used to quantify the protein landscape of the model syntrophic metabolizer, Syntrophomonas wolfei, grown axenically and syntrophically with Methanospirillum hungatei. Remarkably, the abundance of most proteins as represented by normalized spectral abundance factor (NSAF value changed very little between the pure and coculture growth conditions. Among the most abundant proteins detected were GroEL and GroES chaperonins, a small heat shock protein, and proteins involved in electron transfer, beta-oxidation, and ATP synthesis. Several putative energy conservation enzyme systems that utilize NADH and ferredoxin were present. The abundance of an EtfAB2 and the membrane-bound iron-sulfur oxidoreductase (Swol_0698 gene product delineated a potential conduit for electron transfer between acyl-CoA dehydrogenases and membrane redox carriers. Proteins detected only when S. wolfei was grown with M. hungatei included a zinc-dependent dehydrogenase with a GroES domain, whose gene is present in genomes in many organisms capable of syntrophy, and transcriptional regulators responsive to environmental stimuli or the physiological status of the cell. The proteomic analysis revealed an emphasis macromolecular stability and energy metabolism to S. wolfei and presence of regulatory mechanisms responsive to external stimuli and cellular physiological status.

  10. Evolutionary history of barley cultivation in Europe revealed by genetic analysis of extant landraces

    Directory of Open Access Journals (Sweden)

    Jones Huw

    2011-11-01

    Full Text Available Abstract Background Understanding the evolution of cultivated barley is important for two reasons. First, the evolutionary relationships between different landraces might provide information on the spread and subsequent development of barley cultivation, including the adaptation of the crop to new environments and its response to human selection. Second, evolutionary information would enable landraces with similar traits but different genetic backgrounds to be identified, providing alternative strategies for the introduction of these traits into modern germplasm. Results The evolutionary relationships between 651 barley landraces were inferred from the genotypes for 24 microsatellites. The landraces could be divided into nine populations, each with a different geographical distribution. Comparisons with ear row number, caryopsis structure, seasonal growth habit and flowering time revealed a degree of association between population structure and phenotype, and analysis of climate variables indicated that the landraces are adapted, at least to some extent, to their environment. Human selection and/or environmental adaptation may therefore have played a role in the origin and/or maintenance of one or more of the barley landrace populations. There was also evidence that at least some of the population structure derived from geographical partitioning set up during the initial spread of barley cultivation into Europe, or reflected the later introduction of novel varieties. In particular, three closely-related populations were made up almost entirely of plants with the daylength nonresponsive version of the photoperiod response gene PPD-H1, conferring adaptation to the long annual growth season of northern Europe. These three populations probably originated in the eastern Fertile Crescent and entered Europe after the initial spread of agriculture. Conclusions The discovery of population structure, combined with knowledge of associated phenotypes and

  11. Transcriptome analysis of an endoparasitoid wasp Cotesia chilonis (Hymenoptera: Braconidae) reveals genes involved in successful parasitism.

    Science.gov (United States)

    Qi, Yixiang; Teng, Ziwen; Gao, Lingfeng; Wu, Shunfan; Huang, Jia; Ye, Gongyin; Fang, Qi

    2015-04-01

    For successful parasitization, parasitiods usually depend on the chemosensory cues for the selection of hosts, as well as a variety of virulence factors introduced into their hosts to overcome host immunity and prevent rejection of progeny development. In bracovirus-carrying wasps, the symbiotic polydnaviruses act in manipulating development and immunity of hosts. The endoparasitoid Cotesia chilonis carrying bracovirus as a key host immunosuppressive factor is a superior endoparasitoid of rice stem borer, Chilo suppressalis. So far, genomic information for C. chilonis is not available and transcriptomic data may provide valuable resources for global studying on physiological processes of C. chilonis, including chemosensation and parasitism at molecular level. Here, we performed RNA-seq to characterize the transcriptome of C. chilonis adults. We obtained 27,717,892 reads, assembled into 38,318 unigenes with a mean size of 690 bp. Approximately, 62.1% of the unigenes were annotated using NCBI databases. A large number of chemoreception-related genes encoding proteins including odorant receptors, gustatory receptors, odorant-binding proteins, chemosensory proteins, transient receptor potential ion channels, and sensory neuron membrane proteins were identified in silico. Totally, 72 transcripts possessing high identities with the bracovirus-related genes were identified. We investigated the mRNA expression levels of several transcripts at different developmental stages (including egg, larva, pupae, and adult) by quantitative real-time PCR analysis. The results revealed that some genes had adult-specific expression, indicating their potential significance for mating and parasitism. Overall, these results provide comprehensive insights into transcriptomic data of a polydnavirus-carrying parasitoid of a rice pest. PMID:25336406

  12. Comparative genome analysis reveals metabolic versatility and environmental adaptations of Sulfobacillus thermosulfidooxidans strain ST.

    Directory of Open Access Journals (Sweden)

    Xue Guo

    Full Text Available The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant acidophiles within the phylum Firmicutes and requires extremely acidic environments and hypersalinity for optimal growth. However, our understanding of them is still preliminary partly because few genome sequences are available. Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was deciphered to obtain a comprehensive insight into the genetic content and to understand the cellular mechanisms necessary for its survival. Furthermore, the expressions of key genes related with iron and sulfur oxidation were verified by semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of heterogeneity with other Sulfobacillus species. The presence of numerous transposases, genomic islands and complete CRISPR/Cas defence systems testifies to its dynamic evolution consistent with the genome heterogeneity. As expected, S. thermosulfidooxidans encodes a suit of conserved enzymes required for the oxidation of inorganic sulfur compounds (ISCs. The model of sulfur oxidation in S. thermosulfidooxidans was proposed, which showed some different characteristics from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase reductase and heterodisulfide reductase were suggested to play important roles in the sulfur oxidation. Although the iron oxidation ability was observed, some key proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a predicted sulfocyanin is proposed to transfer electrons in the iron oxidation. Furthermore, its carbon metabolism is rather flexible, can perform the transformation of pentose through the oxidative and non-oxidative pentose phosphate pathways and has the ability to take up small organic compounds. It encodes a multitude of heavy metal

  13. Properties of galaxies around AGNs with the most massive supermassive black holes revealed by clustering analysis

    Science.gov (United States)

    Shirasaki, Yuji; Komiya, Yutaka; Ohishi, Masatoshi; Mizumoto, Yoshihiko

    2016-04-01

    We present results of the clustering analysis between active galactic nuclei (AGNs) and galaxies at redshift 0.1-1.0, which was performed to investigate the properties of galaxies associated with the AGNs and reveal the nature of the fueling mechanism of supermassive black holes (SMBHs). We used 8059 AGNs/quasi-stellar objects (QSOs) for which virial masses of individual SMBHs were measured, and divided them into four mass groups.Cross-correlation analysis was performed to reconfirm our previous result that cross-correlation length increases with SMBH mass MBH; we obtained consistent results. A linear bias of AGN for each mass group was measured as 1.47 for MBH = 107.5-108.2 M⊙ and 3.08 for MBH = 109-1010 M⊙. The averaged color and luminosity distributions of galaxies around the AGNs/QSOs were also derived for each mass group. The galaxy color Dopt-IR was estimated from a spectral energy distribution (SED) constructed from a catalog derived by merging the Sloan Digital Sky Survey (SDSS) and the UKIRT Infrared Deep Sky Survey (UKIDSS) catalogs. The distributions of color and luminosity were derived by a subtraction method, which does not require redshift information of galaxies. The main results of this work are as follows. (1) A linear bias increases by a factor of two from the lower-mass group to the highest-mass group. (2) The environment around AGNs with the most massive SMBHs (MBH > 109 M⊙) is dominated by red sequence galaxies. (3) Marginal indication of decline in luminosity function at dimmer side of MIR > -19.5 is found for galaxies around AGNs with MBH = 108.2-109 M⊙ and nearest redshift group (z = 0.1-0.3). These results indicate that AGNs with the most massive SMBHs reside in haloes where a large fraction of galaxies have been transited to the red sequence. The accretion of hot halo gas as well as recycled gas from evolving stars can be one of the plausible mechanisms to fuel the SMBHs above ˜ 109 M⊙.

  14. SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas

    Directory of Open Access Journals (Sweden)

    Behboudi Afrouz

    2011-06-01

    Full Text Available Abstract Background Genomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes. Endometrial carcinoma (EC is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women. Cytogenetic studies of human ECs have not produced very conclusive data, since many of these studies are based on karyotyping of limited number of cases and no really specific karyotypic changes have yet been identified. As the majority of the genes are conserved among mammals, the use of inbred animal model systems may serve as a tool for identification of underlying genes and pathways involved in tumorigenesis in humans. In the present work we used spectral karyotyping (SKY to identify cancer-related aberrations in a well-characterized experimental model for spontaneous endometrial carcinoma in the BDII rat tumor model. Results Analysis of 21 experimental ECs revealed specific nonrandom numerical and structural chromosomal changes. The most recurrent numerical alterations were gains in rat chromosome 4 (RNO4 and losses in RNO15. The most commonly structural changes were mainly in form of chromosomal translocations and were detected in RNO3, RNO6, RNO10, RNO11, RNO12, and RNO20. Unbalanced chromosomal translocations involving RNO3p was the most commonly observed structural changes in this material followed by RNO11p and RNO10 translocations. Conclusion The non-random nature of these events, as documented by their high frequencies of incidence, is suggesting for dynamic selection of these changes during experimental EC tumorigenesis and therefore for their potential contribution into development of this malignancy

  15. Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

    Directory of Open Access Journals (Sweden)

    Henry D Priest

    Full Text Available Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

  16. Carbon sources in the Beaufort Sea revealed by molecular lipid biomarkers and compound specific isotope analysis

    Directory of Open Access Journals (Sweden)

    I. Tolosa

    2012-10-01

    Full Text Available Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids and compound specific isotope analysis of suspended particulate organic matter (SPM and surface sediments of the Mackenzie Shelf and slope (Southeast Beaufort Sea, Arctic Ocean, were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the sedimentary organic matter (OM.

    Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and < 1%, respectively. In marine SPM from the Mackenzie slope, the major contributions were fresh and detrital algal components (> 80% with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60–75% whereas those from the slope contained the highest proportion of fossil (40% and C3 terrestrial plant material (10%. Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the

  17. A comparative phylogenetic analysis of medicinal plant Tribulus terrestris in Northwest India revealed by RAPD and ISSR markers

    OpenAIRE

    ASHWANI KUMAR; NEELAM VERMA

    2012-01-01

    Kumar A, Verma N. 2012. A comparative phylogenetic analysis of medicinal plant Tribulus terrestris in Northwest India revealed by RAPD and ISSR markers. Biodiversitas 13: 107-113. Several DNA marker systems and associated techniques are available today for fingerprinting of plant varieties. A total of 5 RAPD and 8 ISSR primers were used. Amplification of genomic DNA of the 6 genotypes, using RAPD analysis, yielded 164 fragments that could be scored, of which 47 were polymorphic, with an avera...

  18. Phylogeographic analysis reveals significant spatial genetic structure of Incarvillea sinensis as a product of mountain building

    Directory of Open Access Journals (Sweden)

    Chen Shaotian

    2012-04-01

    Full Text Available Abstract Background Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM in 705 individuals from 47 localities. Results A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P  Conclusions The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our study is a typical case of the significance of the uplift of the Qinghai-Tibet Plateau and the Quaternary Glacial in spatial genetic structure of eastern Asian plants, and sheds new light on the evolution of biodiversity in the Qinghai-Tibet Plateau at the intraspecies level.

  19. Force-clamp analysis techniques reveal stretched exponential unfolding kinetics in ubiquitin

    CERN Document Server

    Lannon, Herbert; Brujic, Jasna

    2012-01-01

    Force-clamp spectroscopy reveals the unfolding and disulfide bond rupture times of single protein molecules as a function of the stretching force, point mutations and solvent conditions. The statistics of these times reveal whether the protein domains are independent of one another, the mechanical hierarchy in the polyprotein chain, and the functional form of the probability distribution from which they originate. It is therefore important to use robust statistical tests to decipher the correct theoretical model underlying the process. Here we develop multiple techniques to compare the well-established experimental data set on ubiquitin with existing theoretical models as a case study. We show that robustness against filtering, agreement with a maximum likelihood function that takes into account experimental artifacts, the Kuiper statistic test and alignment with synthetic data all identify the Weibull or stretched exponential distribution as the best fitting model. Our results are inconsistent with recently ...

  20. Single molecule analysis reveals three phases of DNA degradation by an exonuclease

    OpenAIRE

    Lee, Gwangrog; Yoo, Jungmin; Leslie, Benjamin J.; Ha, Taekjip

    2011-01-01

    λ exonuclease degrades one strand of duplex DNA in the 5’-3’ direction to generate a 3’ overhang required for recombination. Its ability to hydrolyze thousands of nucleotides processively is attributed to its ring structure and most studies have focused on the processive phase. Here, we use single molecule FRET to reveal three phases of λ exonuclease reactions: initiation, distributive and processive phases. The distributive phase occurs at early reactions where the 3’ overhang is too short f...

  1. Revealed comparative advantage index: an analysis of export trade in the Austrian district of Burgerland

    OpenAIRE

    Granabetter, Doris

    2016-01-01

    The Austrian District of Burgenland is located in the eastern part of the country. In the last decade, the region has benefited from different subsidy programs from the European Union. The aim of this paper is to analyze and evaluate the export competitiveness of Burgenland in relation to the foreign trade of Austria as a whole from 2010 to 2014, which is the period showing the highest increase in exports since the Iron Curtain fell. The Revealed Comparative Advantage index (RCA) was used ...

  2. Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

    OpenAIRE

    Chou, Wei-Chun; Cheng, An-Lin; Brotto, Marco; Chuang, Chun-Yu

    2014-01-01

    Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy,...

  3. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill;

    2015-01-01

    architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts...... differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator...

  4. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.

    Science.gov (United States)

    Zhang, Hai-Nan; Yang, Lina; Ling, Jian-Ya; Czajkowsky, Daniel M; Wang, Jing-Fang; Zhang, Xiao-Wei; Zhou, Yi-Ming; Ge, Feng; Yang, Ming-Kun; Xiong, Qian; Guo, Shu-Juan; Le, Huang-Ying; Wu, Song-Fang; Yan, Wei; Liu, Bingya; Zhu, Heng; Chen, Zhu; Tao, Sheng-Ce

    2015-12-01

    Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies.

  5. Multilocus analysis reveals large genetic diversity in Kluyveromyces marxianus strains isolated from Parmigiano Reggiano and Pecorino di Farindola cheeses.

    Science.gov (United States)

    Fasoli, Giuseppe; Barrio, Eladio; Tofalo, Rosanna; Suzzi, Giovanna; Belloch, Carmela

    2016-09-16

    In the present study, we have analysed the genetic diversity in Kluyveromyces marxianus isolated from Parmigiano Reggiano and Pecorino di Farindola cheesemaking environment. Molecular typing methods inter-RTL fingerprint and mtDNA RFLPs, as well as, sequence diversity and heterozygosity in the intergenic region between KmSSB1 and KmRIO2 genes and analysis of the mating locus were applied to 54 K. marxianus strains. Inter-RTL fingerprint revealed a large degree of genetic heterogeneity and clustering allowed differentiation of K. marxianus strains from different geographical origins. In general, inter-LTR profiles were more discriminating than RFLPs of mtDNA; however our results also indicate that both techniques could be complementary unveiling different degrees of genetic diversity. Sequence analysis of the intergenic region between KmSSB1 and KmRIO2 genes revealed 26 variable positions in which a double peak could be observed in the sequence chromatogram. Further analysis revealed the presence of heterozygous strains in the K. marxianus population isolated from Parmigiano Reggiano. On the other hand, all strains isolated from Pecorino di Farindola were homozygous. Two very different groups of haplotypes could be observed as well as mixtures between them. Phylogenetic reconstruction divided K. marxianus dairy strains into two separate populations. A few heterozygous strains in an intermediate position between them could also be observed. Mating type locus analysis revealed a large population of diploid strains containing both MATa and MATα alleles and few haploid strains, most of them presenting the MATα allele. Different scenarios explaining the presence and maintaining of homozygous and heterozygous diploids as well as hybrids between them in the Parmigiano Reggiano K. marxianus population are proposed. A principal component analysis supported the large differences between K. marxianus isolated from Parmigiano Reggiano and Pecorino di Farindola. PMID:27294555

  6. Mitochondrial DNA analysis reveals three stocks of yellowfin tuna Thunnus albacares (Bonnaterre, 1788) in Indian waters

    Digital Repository Service at National Institute of Oceanography (India)

    Kunal, S.P.; GirishKumar; Menezes, M.R.; Meena, R.M.

    .001). In addition, spatial analysis of molecular variance identified three genetically heterogeneous groups of yellowfin tuna in Indian waters. Results were further corroborated by significant value of nearest neighbour statistic (S sub(nn)=0.261, P less than...

  7. Proteomic analysis of chromoplasts from six crop species reveals insights into chromoplast function and development

    Science.gov (United States)

    Chromoplasts are unique plastids that accumulate massive amounts of carotenoids. To gain a general and comparative characterization of chromoplast proteins, we performed proteomic analysis of chromoplasts from six carotenoid-rich crops: watermelon, tomato, carrot, orange cauliflower, red papaya, and...

  8. Comparative genome analysis of the oleaginous yeast Trichosporon fermentans reveals its potential applications in lipid accumulation.

    Science.gov (United States)

    Shen, Qi; Chen, Yue; Jin, Danfeng; Lin, Hui; Wang, Qun; Zhao, Yu-Hua

    2016-11-01

    In this work, Trichosporon fermentans CICC 1368, which has been shown to accumulate cellular lipids efficiently using industry-agricultural wastes, was subjected to preliminary genome analysis, yielding a genome size of 31.3 million bases and 12,702 predicted protein-coding genes. Our analysis also showed a high degree of gene duplications and unique genes compared with those observed in other oleaginous yeasts, with 3-4-fold more genes related to fatty acid elongation and degradation compared with those in Rhodosporidium toruloides NP11 and Yarrowia lipolytica CLIB122. Phylogenetic analysis with other oleaginous microbes suggested that the lipogenic capacity of T. fermentans was obtained during evolution after the divergence of genera. Thus, our study provided the first draft genome and comparative analysis of T. fermentans, laying the foundation for its genetic improvement to facilitate cost-effective lipid production. PMID:27664738

  9. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.;

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...

  10. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte; Mørup, Morten; Pedersen, Søren Damkiær;

    2013-01-01

    BACKGROUND: Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data.The aim of this study...... is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas...... expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates...

  11. Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher L Brett

    Full Text Available Protons, the smallest and most ubiquitous of ions, are central to physiological processes. Transmembrane proton gradients drive ATP synthesis, metabolite transport, receptor recycling and vesicle trafficking, while compartmental pH controls enzyme function. Despite this fundamental importance, the mechanisms underlying pH homeostasis are not entirely accounted for in any organelle or organism. We undertook a genome-wide survey of vacuole pH (pH(v in 4,606 single-gene deletion mutants of Saccharomyces cerevisiae under control, acid and alkali stress conditions to reveal the vacuolar pH-stat. Median pH(v (5.27±0.13 was resistant to acid stress (5.28±0.14 but shifted significantly in response to alkali stress (5.83±0.13. Of 107 mutants that displayed aberrant pH(v under more than one external pH condition, functional categories of transporters, membrane biogenesis and trafficking machinery were significantly enriched. Phospholipid flippases, encoded by the family of P4-type ATPases, emerged as pH regulators, as did the yeast ortholog of Niemann Pick Type C protein, implicated in sterol trafficking. An independent genetic screen revealed that correction of pH(v dysregulation in a neo1(ts mutant restored viability whereas cholesterol accumulation in human NPC1(-/- fibroblasts diminished upon treatment with a proton ionophore. Furthermore, while it is established that lumenal pH affects trafficking, this study revealed a reciprocal link with many mutants defective in anterograde pathways being hyperacidic and retrograde pathway mutants with alkaline vacuoles. In these and other examples, pH perturbations emerge as a hitherto unrecognized phenotype that may contribute to the cellular basis of disease and offer potential therapeutic intervention through pH modulation.

  12. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  13. Genetic analysis reveals the complex structure of HIV-1 transmission within defined risk groups

    OpenAIRE

    HUE,S; Pillay, D; Clewley, J. P.; Pybus, O. G.

    2005-01-01

    We explored the epidemic history of HIV-1 subtype B in the United Kingdom using statistical methods that infer the population history of pathogens from sampled gene sequence data. Phylogenetic analysis of HIV-1 pol gene sequences from Britain showed at least six large transmission chains, indicating a genetically variable, but epidemiologically homogeneous, epidemic among men having sex with men. Through coalescent-based analysis we showed that these chains arose through separa...

  14. Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity.

    Directory of Open Access Journals (Sweden)

    John D Gillece

    Full Text Available A recent emergence of Cryptococcus gattii in the Pacific Northwest involves strains that fall into three primarily clonal molecular subtypes: VGIIa, VGIIb and VGIIc. Multilocus sequence typing (MLST and variable number tandem repeat analysis appear to identify little diversity within these molecular subtypes. Given the apparent expansion of these subtypes into new geographic areas and their ability to cause disease in immunocompetent individuals, differentiation of isolates belonging to these subtypes could be very important from a public health perspective. We used whole genome sequence typing (WGST to perform fine-scale phylogenetic analysis on 20 C. gattii isolates, 18 of which are from the VGII molecular type largely responsible for the Pacific Northwest emergence. Analysis both including and excluding (289,586 SNPs and 56,845 SNPs, respectively molecular types VGI and VGIII isolates resulted in phylogenetic reconstructions consistent, for the most part, with MLST analysis but with far greater resolution among isolates. The WGST analysis presented here resulted in identification of over 100 SNPs among eight VGIIc isolates as well as unique genotypes for each of the VGIIa, VGIIb and VGIIc isolates. Similar levels of genetic diversity were found within each of the molecular subtype isolates, despite the fact that the VGIIb clade is thought to have emerged much earlier. The analysis presented here is the first multi-genome WGST study to focus on the C. gattii molecular subtypes involved in the Pacific Northwest emergence and describes the tools that will further our understanding of this emerging pathogen.

  15. Comparative Genome Sequence Analysis Reveals the Extent of Diversity and Conservation for Glycan-Associated Proteins in Burkholderia spp.

    OpenAIRE

    Ong, Hui San; Mohamed, Rahmah; Firdaus-Raih, Mohd

    2012-01-01

    Members of the Burkholderia family occupy diverse ecological niches. In pathogenic family members, glycan-associated proteins are often linked to functions that include virulence, protein conformation maintenance, surface recognition, cell adhesion, and immune system evasion. Comparative analysis of available Burkholderia genomes has revealed a core set of 178 glycan-associated proteins shared by all Burkholderia of which 68 are homologous to known essential genes. The genome sequence compari...

  16. In vitro analysis of phosphorothioate modification of DNA reveals substrate recognition by a multiprotein complex

    Science.gov (United States)

    Cao, Bo; Zheng, Xiaoqing; Cheng, Qiuxiang; Yao, Fen; Zheng, Tao; Ramesh Babu, I.; Zhou, Huchen; Dedon, Peter; You, Delin

    2015-01-01

    A wide variety of prokaryotes possess DNA modifications consisting of sequence-specific phosphorothioates (PT) inserted by members of a five-gene cluster. Recent genome mapping studies revealed two unusual features of PT modifications: short consensus sequences and partial modification of a specific genomic site in a population of bacteria. To better understand the mechanism of target selection of PT modifications that underlies these features, we characterized the substrate recognition of the PT-modifying enzymes termed DptC, D and E in a cell extract system from Salmonella. The results revealed that double-stranded oligodeoxynucleotides underwent de novo PT modification in vitro, with the same modification pattern as in vivo, i. e., GpsAAC/GpsTTC motif. Unexpectedly, in these in vitro analyses we observed no significant effect on PT modification by sequences flanking GAAC/GTTC motif, while PT also occurred in the GAAC/GTTC motif that could not be modified in vivo. Hemi-PT DNA also served as substrate of the PT-modifying enzymes, but not single-stranded DNA. The PT-modifying enzymes were then found to function as a large protein complex, with all of three subunits in tetrameric conformations. This study provided the first demonstration of in vitro DNA PT modification by PT-modifying enzymes that function as a large protein complex. PMID:26213215

  17. Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine; Ahituv, Nadav; Chang, Jessie; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.

    2004-08-20

    COUP-TFII is a central nuclear hormone receptor that tightly regulates the expression of numerous target lipid metabolism genes in vertebrates. However, it remains unclear how COUP-TFII itself is transcriptionally controlled since studies with its promoter and upstream region fail to recapitulate the genes liver expression. In an attempt to identify liver enhancers in the vicinity of COUP-TFII, we employed a comparative genomic approach. Initial comparisons between humans and mice of the 3,470kb gene poor region surrounding COUP-TFII revealed 2,023 conserved non-coding elements. To prioritize a subset of these elements for functional studies, we performed further genomic comparisons with the orthologous pufferfish (Fugu rubripes) locus and uncovered two anciently conserved non-coding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver (HepG2) cells revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity. In addition, an in vivo reporter assay using naked DNA transfer with CNS-66kb linked to luciferase displayed strong reproducible liver expression in adult mice, further supporting its role as a liver enhancer. Together, these studies further support the utility of comparative genomics to uncover gene regulatory sequences based on evolutionary conservation and provide the substrates to better understand the regulation and expression of COUP-TFII.

  18. Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

    Directory of Open Access Journals (Sweden)

    Xiaodong Fang

    2014-09-01

    Full Text Available Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber. Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.

  19. Metagenomic and whole-genome analysis reveals new lineages of gokushoviruses and biogeographic separation in the sea

    Directory of Open Access Journals (Sweden)

    Jessica Myriam Labonté

    2013-12-01

    Full Text Available Much remains to be learned about single-stranded (ss DNA viruses in natural systems, and the evolutionary relationships among them. One of the eight recognized families of ssDNA viruses is the Microviridae, a group of viruses infecting bacteria. In this study we used metagenomic analysis, genome assembly and amplicon sequencing of purified ssDNA to show that bacteriophages belonging to the subfamily Gokushovirinae within the Microviridae are genetically diverse and widespread members of marine microbial communities. Metagenomic analysis of coastal samples from the Gulf of Mexico and British Columbia, Canada, revealed numerous sequences belonging to gokushoviruses and allowed the assembly of five putative genomes with an organization similar to chlamydiamicroviruses. Fragment recruitment to these genomes from different metagenomic data sets is consistent with gokushovirus genotypes being restricted to specific oceanic regions. Conservation among the assembled genomes allowed the design of degenerate primers that target an 800 bp fragment from the gene encoding the major capsid protein. Sequences could be amplified from coastal temperate and subtropical waters, but not from samples collected from the Arctic Ocean, or freshwater lakes. Phylogenetic analysis revealed that most sequences were distantly related to those from cultured representatives. Moreover, the sequences fell into at least seven distinct evolutionary groups, most of which were represented by one of the assembled metagenomes. Our results greatly expand the known sequence space for gokushoviruses, and reveal biogeographic separation and new evolutionary lineages of gokushoviruses in the oceans.

  20. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    Science.gov (United States)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  1. Network Analysis Reveals the Recognition Mechanism for Mannose-binding Lectins

    Science.gov (United States)

    Zhao, Yunjie; Jian, Yiren; Zeng, Chen; Computational Biophysics Lab Team

    The specific carbohydrate binding of mannose-binding lectin (MBL) protein in plants makes it a very useful molecular tool for cancer cell detection and other applications. The biological states of most MBL proteins are dimeric. Using dynamics network analysis on molecular dynamics (MD) simulations on the model protein of MBL, we elucidate the short- and long-range driving forces behind the dimer formation. The results are further supported by sequence coevolution analysis. We propose a general framework for deciphering the recognition mechanism underlying protein-protein interactions that may have potential applications in signaling pathways.

  2. Genome-wide analysis of the Arabidopsis leaf transcriptome reveals interaction of phosphate and sugar metabolism

    DEFF Research Database (Denmark)

    Muller, Renate; Morant, Marc; Jarmer, Hanne Østergaard;

    2007-01-01

    factors individually. The genes exhibiting interactions form three main clusters with different response patterns and functionality of genes. One cluster (cluster 1) most likely represents a regulatory program to support increased growth and development when both P and carbohydrates are ample. Another...... cluster (cluster 3) represents genes induced to alleviate P starvation and these are further induced by carbohydrate accumulation. Thus, interactions between P and Suc reveal two different signaling programs and novel interactions in gene regulation in response to environmental factors. cis......-Regulatory elements were analyzed for each factor and for interaction clusters. PHR1 binding sites were more frequent in promoters of P-regulated genes as compared to the entire Arabidopsis genome, and E2F and PHR1 binding sites were more frequent in interaction clusters 1 and 3, respectively....

  3. Comparative analysis reveals loss of the appetite-regulating peptide hormone ghrelin in falcons.

    Science.gov (United States)

    Seim, Inge; Jeffery, Penny L; Herington, Adrian C; Chopin, Lisa K

    2015-05-15

    Ghrelin and leptin are key peripherally secreted appetite-regulating hormones in vertebrates. Here we consider the ghrelin gene (GHRL) of birds (class Aves), where it has been reported that ghrelin inhibits rather than augments feeding. Thirty-one bird species were compared, revealing that most species harbour a functional copy of GHRL and the coding region for its derived peptides ghrelin and obestatin. We provide evidence for loss of GHRL in saker and peregrine falcons, and this is likely to result from the insertion of an ERVK retrotransposon in intron 0. We hypothesise that the loss of anorexigenic ghrelin is a predatory adaptation that results in increased food-seeking behaviour and feeding in falcons.

  4. Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility.

    Science.gov (United States)

    Alvi, Muhammad A; McArt, Darragh G; Kelly, Paul; Fuchs, Marc-Aurel; Alderdice, Matthew; McCabe, Clare M; Bingham, Victoria; McGready, Claire; Tripathi, Shailesh; Emmert-Streib, Frank; Loughrey, Maurice B; McQuaid, Stephen; Maxwell, Perry; Hamilton, Peter W; Turkington, Richard; James, Jacqueline A; Wilson, Richard H; Salto-Tellez, Manuel

    2015-08-28

    Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p clinically exploitable markers.

  5. Integrated analysis of multiple data sources reveals modular structure of biological networks

    International Nuclear Information System (INIS)

    It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data. Furthermore, we take advantage of the detected modules to provide a reliably functional context for the uncharacterized components within modules. On the other hand, the integration of various protein-protein association information makes our method robust to false-positives, especially for derived protein complexes. More importantly, this simple method can be extended naturally to other types of data fusion and provides a framework for the study of more comprehensive properties of the biological network and other forms of complex networks

  6. Crystal structure analysis reveals functional flexibility in the selenocysteine-specific tRNA from mouse.

    Directory of Open Access Journals (Sweden)

    Oleg M Ganichkin

    Full Text Available BACKGROUND: Selenocysteine tRNAs (tRNA(Sec exhibit a number of unique identity elements that are recognized specifically by proteins of the selenocysteine biosynthetic pathways and decoding machineries. Presently, these identity elements and the mechanisms by which they are interpreted by tRNA(Sec-interacting factors are incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: We applied rational mutagenesis to obtain well diffracting crystals of murine tRNA(Sec. tRNA(Sec lacking the single-stranded 3'-acceptor end ((ΔGCCARNA(Sec yielded a crystal structure at 2.0 Å resolution. The global structure of (ΔGCCARNA(Sec resembles the structure of human tRNA(Sec determined at 3.1 Å resolution. Structural comparisons revealed flexible regions in tRNA(Sec used for induced fit binding to selenophosphate synthetase. Water molecules located in the present structure were involved in the stabilization of two alternative conformations of the anticodon stem-loop. Modeling of a 2'-O-methylated ribose at position U34 of the anticodon loop as found in a sub-population of tRNA(Secin vivo showed how this modification favors an anticodon loop conformation that is functional during decoding on the ribosome. Soaking of crystals in Mn(2+-containing buffer revealed eight potential divalent metal ion binding sites but the located metal ions did not significantly stabilize specific structural features of tRNA(Sec. CONCLUSIONS/SIGNIFICANCE: We provide the most highly resolved structure of a tRNA(Sec molecule to date and assessed the influence of water molecules and metal ions on the molecule's conformation and dynamics. Our results suggest how conformational changes of tRNA(Sec support its interaction with proteins.

  7. Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis FlowersW

    NARCIS (Netherlands)

    Ginglinger, J.F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T.G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullman, P.; Verstappen, F.W.A.; Bouwmeester, H.J.

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus

  8. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

    DEFF Research Database (Denmark)

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M;

    2014-01-01

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform o...

  9. A Bayesian multidimensional scaling procedure for the spatial analysis of revealed choice data

    NARCIS (Netherlands)

    DeSarbo, WS; Kim, Y; Fong, D

    1999-01-01

    We present a new Bayesian formulation of a vector multidimensional scaling procedure for the spatial analysis of binary choice data. The Gibbs sampler is gainfully employed to estimate the posterior distribution of the specified scalar products, bilinear model parameters. The computational procedure

  10. Meta-analysis reveals a critical period for management of powdery mildew on Hop cones

    Science.gov (United States)

    Results of 28 field trials conducted over a 12-year period investigating management of hop powdery mildew caused by Podosphaera macularis were quantitatively summarized by meta-analysis to compare product efficacy and use patterns by mode of action as defined by Fungicide Resistance Action Committe...

  11. Vacuolar invertase regulates elongation of Arabidopsis thaliana roots as revealed by QTL and mutant analysis.

    NARCIS (Netherlands)

    Sergeeva, L.I.; Keurentjes, J.J.B.; Bentsink, L.; Vonk, J.; Plas, van der L.H.W.; Koornneef, M.; Vreugdenhil, D.

    2006-01-01

    The possible role of the sucrose-splitting enzymes sucrose synthase and invertase in elongating roots and hypocotyls of Arabidopsis was tested by using a combination of histochemical methods and quantitative trait locus (QTL) analysis. Lengths of roots and hypocotyls correlated better with invertase

  12. Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

    Directory of Open Access Journals (Sweden)

    Ana F A Parente

    Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

  13. Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Mark R. Winter

    2015-10-01

    Full Text Available Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex.

  14. Potential analysis reveals changing number of climate states during the last 60 kyr

    Directory of Open Access Journals (Sweden)

    V. N. Livina

    2010-02-01

    Full Text Available We develop and apply a new statistical method of potential analysis for detecting the number of states of a geophysical system, from its recorded time series. Estimation of the degree of a polynomial potential allows us to derive the number of potential wells in a system. The method correctly detects changes in the number of wells in artificial data. In ice-core proxy records of Greenland paleotemperature, a reduction in the number of climate states from two to one is detected sometime prior to the last glacial maximum (LGM, 23–19 kyr BP. This result is also found in analysis of Greenland Ca data. The bifurcation can be interpreted as loss of stability of the warm interstadial state of the Dansgaard-Oeschger (DO events. The proposed method can be applied to a wide range of geophysical time series exhibiting bifurcations.

  15. Comparative proteomic analysis reveals mite (Varroa destructor) resistance-related proteins in Eastern honeybees (Apis cerana).

    Science.gov (United States)

    Ji, T; Shen, F; Liu, Z; Yin, L; Shen, J; Liang, Q; Luo, Y X

    2015-08-21

    The mite (Varroa destructor) has become the greatest threat to apiculture worldwide. As the original host of the mite, Apis cerana can effectively resist the mite. An increased understanding of the resistance mechanisms of Eastern honeybees against V. destructor may help researchers to protect other species against these parasites. In this study, the proteomes of 4 Apis cerana colonies were analyzed using an isobaric tag for relative and absolute quantitation technology. We determined the differences in gene and protein expression between susceptible and resistant colonies that were either unchallenged or challenged by V. destructor. The results showed that a total of 1532 proteins were identified. Gene Ontology enrichment analysis suggested that the transcription factors and basic metabolic and respiratory processes were efficient and feasible factors controlling this resistance, and 12 differentially expressed proteins were identified in Venn analysis. The results were validated by quantitative polymerase chain reaction. This study may provide insight into the genetic mechanisms underlying the resistance of honeybee to mites.

  16. Phylogenetic analysis of 48 gene families revealing relationships between Hagfishes, Lampreys, and Gnathostomata

    Institute of Scientific and Technical Information of China (English)

    Shuiyan Yu; Weiwei Zhang; Ling Li; Huifang Huang; Fei Ma; Qingwei Li

    2008-01-01

    It has become clear that the extant vertebrates are divided into three major groups, that is, hagfishes, lampreys, and jawed vertebrates.Morphological and molecular studies, however, have resulted in conflicting views with regard m their interrelationships. To clarify the phylogenetic relationships between them, 48 orthologous protein-coding gene families were analyzed. Even as the analysis of 34 nuclear gene families supported the monophyly of cyclostomes, the analysis of 14 mitochondrial gene families suggested a closer relationship between lampreys and gnathostomes compared to hagfishes. Lampreys were sister group of gnathostomes. The results of this study sup-ported the eyclostomes. Choice of outgroup, tree-making methods, and software may affect the phylogenetic prediction, which may have caused much debate over the subject. Development of new methods for tackling such problems is still necessary.

  17. Histopathological and ultrastructural analysis of vestibular endorgans in Meniere's disease reveals basement membrane pathology

    Directory of Open Access Journals (Sweden)

    McCall Andrew A

    2009-06-01

    Full Text Available Abstract Background We report the systematic analysis of the ultrastructural and cytological histopathology of vestibular endorgans acquired from labyrinthectomy in Meniere's disease. Methods 17 subjects with intractable Meniere's disease and ipsilateral non-serviceable hearing presenting to the Neurotology Clinic from 1997 to 2006 who chose ablative labyrinthectomy (average age = 62 years; range 29–83 years participated. The average duration of symptoms prior to surgery was 7 years (range 1–20 years. Results Nearly all vestibular endorgans demonstrated varying degrees of degeneration. A monolayer of epithelial cells occurred significantly more frequently in the horizontal cristae (12/13 = 92% (p Conclusion Systematic histopathological analysis of the vestibular endorgans from Meniere's disease demonstrated neuroepithelial degeneration which was highly correlated with an associated BM thickening. Other findings included hair cell and supporting cell microvessicles, increased intercellular clear spaces in the stroma, and endothelial cell vacuolization and stromal perivascular BM thickening.

  18. Proteomic analysis of regenerated rabbit lenses reveal crystallin expression characteristic of adult rabbits

    OpenAIRE

    Liu, Xialin; Min ZHANG; Liu, Yuhua; Challa, Pratap; Gonzalez, Pedro; Liu, Yizhi

    2008-01-01

    Purpose To explore lens crystallin characteristics and morphology of rabbit regenerated lenses in comparison with wild type natural lenses by means of proteomic analysis and histological assay. Methods The lens regeneration model of the New Zealand rabbit was established, and lens regeneration was observed by slit lamp examination and photography. A histological assay was evaluated under light microscopy and transmission electron microscopy (TEM). Protein samples of regenerated lenses were co...

  19. Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma

    OpenAIRE

    Palavalli, Lavanya H.; Prickett, Todd D.; Wunderlich, John R.; Wei, Xiaomu; Burrell, Allison S.; Porter-Gill, Patricia; Davis, Sean; Wang, Chenwei; Cronin, Julia C.; Agrawal, Neena S.; Lin, Jimmy C.; Westbroek, Wendy; Hoogstraten-Miller, Shelley; Molinolo, Alfredo A; Fetsch, Patricia

    2009-01-01

    A mutational analysis of the matrix metalloproteinase (MMP) gene family in human melanoma identified somatic mutations in 23% of melanomas. Five mutations in one of the most commonly mutated genes, MMP8, reduced MMP enzyme activity. Expression of wild-type but not mutant MMP8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression.

  20. Balkanized Research in Ecological Engineering Revealed by a Bibliometric Analysis of Earthworms and Ecosystem Services

    OpenAIRE

    Blouin, Manuel; Sery, Nicolas; Cluzeau, Daniel; Brun, Jean-Jacques; Bédécarrats, Alain

    2013-01-01

    International audience Energy crisis, climate changes, and biodiversity losses have reinforced the drive for more ecologically based approaches for environmental management. Such approaches are characterized by the use of organisms rather than energy-consuming technologies. Although earthworms are believed to be potentially useful organisms for managing ecosystem services, there is actually no quantification of such a trend in literature. This bibliometric analysis aimed to measure the evo...

  1. Stable isotope analysis of vertebrae reveals ontogenetic changes in habitat in an endothermic pelagic shark

    OpenAIRE

    Carlisle, Aaron B.; Goldman, Kenneth J.; Litvin, Steven Y.; Madigan, Daniel J; Bigman, Jennifer S.; Alan M Swithenbank; Kline, Thomas C.; Barbara A. Block

    2015-01-01

    Ontogenetic changes in habitat are driven by shifting life-history requirements and play an important role in population dynamics. However, large portions of the life history of many pelagic species are still poorly understood or unknown. We used a novel combination of stable isotope analysis of vertebral annuli, Bayesian mixing models, isoscapes and electronic tag data to reconstruct ontogenetic patterns of habitat and resource use in a pelagic apex predator, the salmon shark (Lamna ditropis...

  2. Analysis of image versus position, scale and direction reveals pattern texture anisotropy

    Directory of Open Access Journals (Sweden)

    Roland eLehoucq

    2015-01-01

    Full Text Available Pattern heterogeneities and anisotropies often carry significant physical information. We provide a toolbox which: (i cumulates analysis in terms of position, direction and scale; (ii is as general as possible; (iii is simple and fast to understand, implement, execute and exploit.It consists in dividing the image into analysis boxes at a chosen scale; in each box an ellipse (the inertia tensor is fitted to the signal and thus determines the direction in which the signal is more present. This tensor can be averaged in position and/or be used to study the dependence with scale. This choice is formally linked with Leray transforms and anisotropic wavelet analysis. Such protocol is intutively interpreted and consistent with what the eye detects: relevant scales, local variations in space, priviledged directions. It is fast and parallelizable.Its several variants are adaptable to the user's data and needs. It is useful to statistically characterize anisotropies of 2D or 3D patterns in which individual objects are not easily distinguished, with only minimal pre-processing of the raw image, and more generally applies to data in higher dimensions.It is less sensitive to edge effects, and thus better adapted for a multiscale analysis down to small scale boxes, than pair correlation function or Fourier transform.Easy to understand and implement,it complements more sophisticated methods such as Hough transform or diffusion tensor imaging.We use it on various fracture patterns (sea ice cover, thin sections of granite, granular materials, to pinpoint the maximal anisotropy scales. The results are robust to noise and to user choices. This toolbox could turn also useful for granular materials, hard condensed matter, geophysics, thin films, statistical mechanics, characterisation of networks, fluctuating amorphous systems, inhomogeneous and disordered systems, or medical imaging, among others.

  3. Cell proliferation in the Drosophila adult brain revealed by clonal analysis and bromodeoxyuridine labelling

    OpenAIRE

    Brand Andrea H; Egger Boris; von Trotha Jakob W

    2009-01-01

    Abstract Background The production of new neurons during adulthood and their subsequent integration into a mature central nervous system have been shown to occur in all vertebrate species examined to date. However, the situation in insects is less clear and, in particular, it has been reported that there is no proliferation in the Drosophila adult brain. Results We report here, using clonal analysis and 5'-bromo-2'-deoxyuridine (BrdU) labelling, that cell proliferation does occur in the Droso...

  4. Microarray analysis reveals overlapping and specific transcriptional responses to different plant hormones in rice

    OpenAIRE

    Garg, Rohini; Tyagi, Akhilesh K.; Jain, Mukesh

    2012-01-01

    Hormones exert pleiotropic effects on plant growth and development throughout the life cycle. Many of these effects are mediated at molecular level via altering gene expression. In this study, we investigated the exogenous effect of plant hormones, including auxin, cytokinin, abscisic acid, ethylene, salicylic acid and jasmonic acid, on the transcription of rice genes at whole genome level using microarray. Our analysis identified a total of 4171 genes involved in several biological processes...

  5. A Simple Force-Motion Relation for Migrating Cells Revealed by Multipole Analysis of Traction Stress

    OpenAIRE

    Tanimoto, Hirokazu; Sano, Masaki

    2014-01-01

    For biophysical understanding of cell motility, the relationship between mechanical force and cell migration must be uncovered, but it remains elusive. Since cells migrate at small scale in dissipative circumstances, the inertia force is negligible and all forces should cancel out. This implies that one must quantify the spatial pattern of the force instead of just the summation to elucidate the force-motion relation. Here, we introduced multipole analysis to quantify the traction stress dyna...

  6. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus)

    OpenAIRE

    Thomas E Dowling; Turner, Thomas F.; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Paul C Marsh

    2013-01-01

    Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is m...

  7. Vacuolar invertase regulates elongation of Arabidopsis thaliana roots as revealed by QTL and mutant analysis

    OpenAIRE

    Sergeeva, L.I.; Keurentjes, J. J. B.; Bentsink, L.; Vonk, J.; Plas, van der, M..; Koornneef, M; Vreugdenhil, D.

    2006-01-01

    The possible role of the sucrose-splitting enzymes sucrose synthase and invertase in elongating roots and hypocotyls of Arabidopsis was tested by using a combination of histochemical methods and quantitative trait locus (QTL) analysis. Lengths of roots and hypocotyls correlated better with invertase activities than with sucrose synthase activities. The highest correlations were observed with activities in the elongating zones of roots. The genetic basis of these correlations was studied by us...

  8. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  9. BAHAMAS: New Analysis of Type Ia Supernovae Reveals Inconsistencies with Standard Cosmology

    Science.gov (United States)

    Shariff, Hikmatali; Jiao, Xiyun; Trotta, Roberto; van Dyk, David A.

    2016-08-01

    We present results obtained by applying our BAyesian HierArchical Modeling for the Analysis of Supernova cosmology (BAHAMAS) software package to the 740 spectroscopically confirmed supernovae of type Ia (SNe Ia) from the “Joint Light-curve Analysis” (JLA) data set. We simultaneously determine cosmological parameters and standardization parameters, including corrections for host galaxy mass, residual scatter, and object-by-object intrinsic magnitudes. Combining JLA and Planck data on the cosmic microwave background, we find significant discrepancies in cosmological parameter constraints with respect to the standard analysis: we find {{{Ω }}}{{m}}=0.399+/- 0.027, 2.8σ higher than previously reported, and w=-0.910+/- 0.045, 1.6σ higher than the standard analysis. We determine the residual scatter to be {σ }{{res}}=0.104+/- 0.005. We confirm (at the 95% probability level) the existence of two subpopulations segregated by host galaxy mass, separated at {{log}}10(M/{M}ȯ )=10, differing in mean intrinsic magnitude by 0.055 ± 0.022 mag, lower than previously reported. Cosmological parameter constraints, however, are unaffected by the inclusion of corrections for host galaxy mass. We find ˜ 4σ evidence for a sharp drop in the value of the color correction parameter, β (z), at a redshift {z}t=0.662+/- 0.055. We rule out some possible explanations for this behavior, which remains unexplained.

  10. BAHAMAS: New Analysis of Type Ia Supernovae Reveals Inconsistencies with Standard Cosmology

    Science.gov (United States)

    Shariff, Hikmatali; Jiao, Xiyun; Trotta, Roberto; van Dyk, David A.

    2016-08-01

    We present results obtained by applying our BAyesian HierArchical Modeling for the Analysis of Supernova cosmology (BAHAMAS) software package to the 740 spectroscopically confirmed supernovae of type Ia (SNe Ia) from the “Joint Light-curve Analysis” (JLA) data set. We simultaneously determine cosmological parameters and standardization parameters, including corrections for host galaxy mass, residual scatter, and object-by-object intrinsic magnitudes. Combining JLA and Planck data on the cosmic microwave background, we find significant discrepancies in cosmological parameter constraints with respect to the standard analysis: we find {{{Ω }}}{{m}}=0.399+/- 0.027, 2.8σ higher than previously reported, and w=-0.910+/- 0.045, 1.6σ higher than the standard analysis. We determine the residual scatter to be {σ }{{res}}=0.104+/- 0.005. We confirm (at the 95% probability level) the existence of two subpopulations segregated by host galaxy mass, separated at {{log}}10(M/{M}⊙ )=10, differing in mean intrinsic magnitude by 0.055 ± 0.022 mag, lower than previously reported. Cosmological parameter constraints, however, are unaffected by the inclusion of corrections for host galaxy mass. We find ˜ 4σ evidence for a sharp drop in the value of the color correction parameter, β (z), at a redshift {z}t=0.662+/- 0.055. We rule out some possible explanations for this behavior, which remains unexplained.

  11. Microsatellite analysis reveals genetically distinct populations of red pine (Pinus resinosa, Pinaceae).

    Science.gov (United States)

    Boys, Jacquelyn; Cherry, Marilyn; Dayanandan, Selvadurai

    2005-05-01

    Red pine (Pinus resinosa Ait.) is an ecologically and economically important forest tree species of northeastern North America and is considered one of the most genetically depauperate conifer species in the region. We have isolated and characterized 13 nuclear microsatellite loci by screening a partial genomic library with di-, tri-, and tetranucleotide repeat oligonucleotide probes. In an analysis of over 500 individuals representing 17 red pine populations from Manitoba through Newfoundland, five polymorphic microsatellite loci with an average of nine alleles per locus were identified. The mean expected and observed heterozygosity values were 0.508 and 0.185, respectively. Significant departures from Hardy-Weinberg equilibrium with excess homozygosity indicating high levels of inbreeding were evident in all populations studied. The population differentiation was high with 28-35% of genetic variation partitioned among populations. The genetic distance analysis showed that three northeastern (two Newfoundland and one New Brunswick) populations are genetically distinct from the remaining populations. The coalescence-based analysis suggests that "northeastern" and "main" populations likely became isolated during the most recent Pleistocene glacial period, and severe population bottlenecks may have led to the evolution of a highly selfing mating system in red pine. PMID:21652464

  12. Metabolomic analysis reveals mechanism of antioxidant butylated hydroxyanisole on lipid accumulation in Crypthecodinium cohnii.

    Science.gov (United States)

    Sui, Xiao; Niu, Xiangfeng; Shi, Mengliang; Pei, Guangsheng; Li, Jinghan; Chen, Lei; Wang, Jiangxin; Zhang, Weiwen

    2014-12-24

    The heterotrophic dinoflagellate alga Crypthecodinium cohnii is known to accumulate lipids with a high fraction of docosahexaenoic acid (DHA). In this study, we first evaluated two antioxidant compounds, butylated hydroxyanisole (BHA) and propyl gallate (PG), for their effects on lipid accumulation in C. cohnii. The results showed that antioxidant BHA could increase lipid accumulation in C. cohnii by 8.80% at a final concentration of 30 μM, while PG had no obvious effect on lipid accumulation at the tested concentrations. To decipher the molecular mechanism responsible for the increased lipid accumulation by BHA, we employed an integrated GC-MS and LC-MS metabolomic approach to determine the time-series metabolic profiles with or without BHA, and then subjected the metabolomic data to a principal component analysis (PCA) and a weighted gene coexpression network analysis (WGCNA) network analyses to identify the key metabolic modules and metabolites possibly relevant to the increased lipid accumulation. LC-MS analysis showed that several metabolites, including NADPH, could be important for the stimulation role of BHA on lipid accumulation. Meanwhile GC-MS and network analyses allowed identification of eight metabolic modules and nine hub metabolites possibly relevant to the stimulation role of BHA in C. cohnii. The study provided a metabolomics view of the BHA mode of action on lipid accumulation in C. cohnii, and the information could be valuable for a better understanding of antioxidant effects on lipid accumulation in other microalgae as well. PMID:25436856

  13. Antennal RNA-sequencing analysis reveals evolutionary aspects of chemosensory proteins in the carpenter ant, Camponotus japonicus.

    Science.gov (United States)

    Hojo, Masaru K; Ishii, Kenichi; Sakura, Midori; Yamaguchi, Katsushi; Shigenobu, Shuji; Ozaki, Mamiko

    2015-01-01

    Chemical communication is essential for the coordination of complex organisation in ant societies. Recent comparative genomic approaches have revealed that chemosensory genes are diversified in ant lineages, and suggest that this diversification is crucial for social organisation. However, how such diversified genes shape the peripheral chemosensory systems remains unknown. In this study, we annotated and analysed the gene expression profiles of chemosensory proteins (CSPs), which transport lipophilic compounds toward chemosensory receptors in the carpenter ant, Camponotus japonicus. Transcriptome analysis revealed 12 CSP genes and phylogenetic analysis showed that 3 of these are lineage-specifically expanded in the clade of ants. RNA sequencing and real-time quantitative polymerase chain reaction revealed that, among the ant specific CSP genes, two of them (CjapCSP12 and CjapCSP13) were specifically expressed in the chemosensory organs and differentially expressed amongst ant castes. Furthermore, CjapCSP12 and CjapCSP13 had a ratio of divergence at non-synonymous and synonymous sites (dN/dS) greater than 1, and they were co-expressed with CjapCSP1, which is known to bind cuticular hydrocarbons. Our results suggested that CjapCSP12 and CjapCSP13 were functionally differentiated for ant-specific chemosensory events, and that CjapCSP1, CjapCSP12, and CjapCSP13 work cooperatively in the antennal chemosensilla of worker ants. PMID:26310137

  14. Antennal RNA-sequencing analysis reveals evolutionary aspects of chemosensory proteins in the carpenter ant, Camponotus japonicus.

    Science.gov (United States)

    Hojo, Masaru K; Ishii, Kenichi; Sakura, Midori; Yamaguchi, Katsushi; Shigenobu, Shuji; Ozaki, Mamiko

    2015-08-27

    Chemical communication is essential for the coordination of complex organisation in ant societies. Recent comparative genomic approaches have revealed that chemosensory genes are diversified in ant lineages, and suggest that this diversification is crucial for social organisation. However, how such diversified genes shape the peripheral chemosensory systems remains unknown. In this study, we annotated and analysed the gene expression profiles of chemosensory proteins (CSPs), which transport lipophilic compounds toward chemosensory receptors in the carpenter ant, Camponotus japonicus. Transcriptome analysis revealed 12 CSP genes and phylogenetic analysis showed that 3 of these are lineage-specifically expanded in the clade of ants. RNA sequencing and real-time quantitative polymerase chain reaction revealed that, among the ant specific CSP genes, two of them (CjapCSP12 and CjapCSP13) were specifically expressed in the chemosensory organs and differentially expressed amongst ant castes. Furthermore, CjapCSP12 and CjapCSP13 had a ratio of divergence at non-synonymous and synonymous sites (dN/dS) greater than 1, and they were co-expressed with CjapCSP1, which is known to bind cuticular hydrocarbons. Our results suggested that CjapCSP12 and CjapCSP13 were functionally differentiated for ant-specific chemosensory events, and that CjapCSP1, CjapCSP12, and CjapCSP13 work cooperatively in the antennal chemosensilla of worker ants.

  15. Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

    Directory of Open Access Journals (Sweden)

    Nordlund Henri R

    2005-03-01

    Full Text Available Abstract Background A chicken egg contains several biotin-binding proteins (BBPs, whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. Results Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. Conclusion We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins.

  16. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

    Directory of Open Access Journals (Sweden)

    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  17. Regulation of BZR1 in fruit ripening revealed by iTRAQ proteomics analysis

    Science.gov (United States)

    Liu, Lihong; Liu, Haoran; Li, Shuo; Zhang, Xin; Zhang, Min; Zhu, Ning; Dufresne, Craig P.; Chen, Sixue; Wang, Qiaomei

    2016-01-01

    Fruit ripening is a complex and genetically programmed process. Brassinosteroids (BRs) play an essential role in plant growth and development, including fruit ripening. As a central component of BR signaling, the transcription factor BZR1 is involved in fruit development in tomato. However, the transcriptional network through which BZR1 regulates fruit ripening is mostly unknown. In this study, we use isobaric tags for relative and absolute quantitation (iTRAQ) labeling technology to explore important proteins regulated by BZR1 in two independent tomato transgenic lines over-expressing BZR1-1D at four ripening stages, identifying 411 differentially expressed proteins. These proteins were implicated in light reaction, plant hormone pathways and cell-wall-related metabolism, etc. The ‘light reaction’ metabolic pathway was identified as a markedly enhanced pathway by BZR1 during tomato fruit ripening. The protein level of a probable 2-oxoglutarate-dependent dioxygenase 2-ODD2, involved in gibberellin biosynthesis was significantly increased at all four developmental and ripening stages. The results reveal molecular links between BR signaling pathway and downstream components involved in multiple ripening-associated events during tomato fruit ripening, which will provide new insights into the molecular mechanisms underlying tomato ripening regulatory networks, and be potential in understanding BR-regulated fruit ripening. PMID:27680870

  18. Proteomic analysis reveals a novel function of the kinase Sat4p in Saccharomyces cerevisiae mitochondria.

    Directory of Open Access Journals (Sweden)

    Uta Gey

    Full Text Available The Saccharomyces cerevisiae kinase Sat4p has been originally identified as a protein involved in salt tolerance and stabilization of plasma membrane transporters, implicating a cytoplasmic localization. Our study revealed an additional mitochondrial (mt localization, suggesting a dual function for Sat4p. While no mt related phenotype was observed in the absence of Sat4p, its overexpression resulted in significant changes of a specific mitochondrial subproteome. As shown by a comparative two dimensional difference gel electrophoresis (2D-DIGE approach combined with mass spectrometry, particularly two groups of proteins were affected: the iron-sulfur containing aconitase-type proteins (Aco1p, Lys4p and the lipoamide-containing subproteome (Lat1p, Kgd2p and Gcv3p. The lipoylation sites of all three proteins could be assigned by nanoLC-MS/MS to Lys75 (Lat1p, Lys114 (Kgd2p and Lys102 (Gcv3p, respectively. Sat4p overexpression resulted in accumulation of the delipoylated protein variants and in reduced levels of aconitase-type proteins, accompanied by a decrease in the activities of the respective enzyme complexes. We propose a regulatory role of Sat4p in the late steps of the maturation of a specific subset of mitochondrial iron-sulfur cluster proteins, including Aco1p and lipoate synthase Lip5p. Impairment of the latter enzyme may account for the observed lipoylation defects.

  19. Characterization and phylogenetic analysis of -gliadin gene sequences reveals significant genomic divergence in Triticeae species

    Indian Academy of Sciences (India)

    Guang-Rong Li; Tao Lang; En-Nian Yang; Cheng Liu; Zu-Jun Yang

    2014-12-01

    Although the unique properties of wheat -gliadin gene family are well characterized, little is known about the evolution and genomic divergence of -gliadin gene family within the Triticeae. We isolated a total of 203 -gliadin gene sequences from 11 representative diploid and polyploid Triticeae species, and found 108 sequences putatively functional. Our results indicate that -gliadin genes may have possibly originated from wild Secale species, where the sequences contain the shortest repetitive domains and display minimum variation. A miniature inverted-repeat transposable element insertion is reported for the first time in -gliadin gene sequence of Thinopyrum intermedium in this study, indicating that the transposable element might have contributed to the diversification of -gliadin genes family among Triticeae genomes. The phylogenetic analyses revealed that the -gliadin gene sequences of Dasypyrum, Australopyrum, Lophopyrum, Eremopyrum and Pseudoroengeria species have amplified several times. A search for four typical toxic epitopes for celiac disease within the Triticeae -gliadin gene sequences showed that the -gliadins of wild Secale, Australopyrum and Agropyron genomes lack all four epitopes, while other Triticeae species have accumulated these epitopes, suggesting that the evolution of these toxic epitopes sequences occurred during the course of speciation, domestication or polyploidization of Triticeae.

  20. Structure-function analysis of a bacterial deoxyadenosine kinase reveals the basis for substrate specificity.

    Science.gov (United States)

    Welin, Martin; Wang, Liya; Eriksson, Staffan; Eklund, Hans

    2007-03-01

    Deoxyribonucleoside kinases (dNKs) catalyze the transfer of a phosphoryl group from ATP to a deoxyribonucleoside (dN), a key step in DNA precursor synthesis. Recently structural information concerning dNKs has been obtained, but no structure of a bacterial dCK/dGK enzyme is known. Here we report the structure of such an enzyme, represented by deoxyadenosine kinase from Mycoplasma mycoides subsp. mycoides small colony type (Mm-dAK). Superposition of Mm-dAK with its human counterpart's deoxyguanosine kinase (dGK) and deoxycytidine kinase (dCK) reveals that the overall structures are very similar with a few amino acid alterations in the proximity of the active site. To investigate the substrate specificity, Mm-dAK has been crystallized in complex with dATP and dCTP, as well as the products dCMP and dCDP. Both dATP and dCTP bind to the enzyme in a feedback-inhibitory manner with the dN part in the deoxyribonucleoside binding site and the triphosphates in the P-loop. Substrate specificity studies with clinically important nucleoside analogs as well as several phosphate donors were performed. Thus, in this study we combine structural and kinetic data to gain a better understanding of the substrate specificity of the dCK/dGK family of enzymes. The structure of Mm-dAK provides a starting point for making new anti bacterial agents against pathogenic bacteria.

  1. Service innovation management practices in the telecommunications industry: what does cross country analysis reveal?

    Science.gov (United States)

    Rahman, Syed Abidur; Taghizadeh, Seyedeh Khadijeh; Ramayah, T; Ahmad, Noor Hazlina

    2015-01-01

    Service innovation management practice is currently being widely scrutinized mainly in the developed countries, where it has been initiated. The current study attempts to propose a framework and empirically validate and explain the service innovation practices for successful performance in the telecommunications industry of two developing countries, Malaysia and Bangladesh. The research framework proposes relationships among organisational culture, operating core (innovation process, cross-functional organisation, and implementation of tools/technology), competition-informed pricing, and performance. A total of 176 usable data from both countries are analysed for the purpose of the research. The findings show that organisational culture tends to be more influential on innovation process and cross-functional organisation in Malaysian telecommunication industry. In contrast, implementation of tools/technology plays a more instrumental role in competition-informed pricing practices in Bangladesh. This study revealed few differences in the innovation management practices between two developing countries. The findings have strategic implications for the service sectors in both the developing countries regarding implementation of innovative enterprises, especially in Bangladesh where innovation is the basis for survival. Testing the innovation management practices in the developing countries perhaps contains uniqueness in the field of innovation management. PMID:26722630

  2. Phosphoproteome analysis of the MAPK pathway reveals previously undetected feedback mechanisms.

    Science.gov (United States)

    Gnad, Florian; Doll, Sophia; Song, Kyung; Stokes, Matthew P; Moffat, John; Liu, Bonnie; Arnott, David; Wallin, Jeffrey; Friedman, Lori S; Hatzivassiliou, Georgia; Belvin, Marcia

    2016-07-01

    The RAS-RAF-MEK-ERK (MAPK) pathway is prevalently perturbed in cancer. Recent large-scale sequencing initiatives profiled thousands of tumors providing insight into alterations at the DNA and RNA levels. These efforts confirmed that key nodes of the MAPK pathway, in particular KRAS and BRAF, are among the most frequently altered proteins in cancer. The establishment of targeted therapies, however, has proven difficult. To decipher the underlying challenges, it is essential to decrypt the phosphorylation network spanned by the MAPK core axis. Using mass spectrometry we identified 2241 phosphorylation sites on 1020 proteins, and measured their responses to inhibition of MEK or ERK. Multiple phosphorylation patterns revealed previously undetected feedback, as upstream signaling nodes, including receptor kinases, showed changes at the phosphorylation level. We provide a dataset rich in potential therapeutic targets downstream of the MAPK cascade. By integrating TCGA (The Cancer Genome Atlas) data, we highlight some downstream phosphoproteins that are frequently altered in cancer. All MS data have been deposited in the ProteomeXchange with identifier PXD003908 (http://proteomecentral.proteomexchange.org/dataset/PXD003908). PMID:27273156

  3. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

    Science.gov (United States)

    Lee, Kim-Chung; Tam, Emily W T; Lo, Ka-Ching; Tsang, Alan K L; Lau, Candy C Y; To, Kelvin K W; Chan, Jasper F W; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2015-06-17

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

  4. Transcriptome analysis reveals novel genes involved in nonhost response to bacterial infection in tobacco.

    Science.gov (United States)

    Daurelio, Lucas Damián; Petrocelli, Silvana; Blanco, Francisca; Holuigue, Loreto; Ottado, Jorgelina; Orellano, Elena Graciela

    2011-03-01

    Plants are continuously exposed to pathogen challenge. The most common defense response to pathogenic microorganisms is the nonhost response, which is usually accompanied by transcriptional changes. In order to identify genes involved in nonhost resistance, we evaluated the tobacco transcriptome profile after infection with Xanthomonas axonopodis pv. citri (Xac), a nonhost phytopathogenic bacterium. cDNA-amplified fragment length polymorphism was used to identify differentially expressed transcripts in tobacco leaves infected with Xac at 2, 8 and 24h post-inoculation. From a total of 2087 transcript-derived fragments (TDFs) screened (approximately 20% of the tobacco transcriptome), 316 TDFs showed differential expression. Based on sequence similarities, 82 differential TDFs were identified and assigned to different functional categories: 56 displayed homology to genes with known functions, 12 to proteins with unknown functions and 14 did not have a match. Real-time PCR was carried out with selected transcripts to confirm the expression pattern obtained. The results reveal novel genes associated with nonhost resistance in plant-pathogen interaction in tobacco. These novel genes could be included in future strategies of molecular breeding for nonhost disease resistance. PMID:20828873

  5. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

    Directory of Open Access Journals (Sweden)

    Kim-Chung Lee

    2015-06-01

    Full Text Available Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxybenzoic acid possesses a structure similar to those of aspirin [2-(acetoxybenzoic acid] and salicylic acid (2-hydroxybenzoic acid. Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid are virulent factors of the pathogenic Aspergillus species.

  6. A novel genome-wide full- length kinesin prediction analysis reveals additional mammalian kinesins

    Institute of Scientific and Technical Information of China (English)

    XUE Yu; LIU Dan; FU Chuanhai; DOU Zhen; ZHOU Qing; YAO Xuebiao

    2006-01-01

    Kinesin superfamily of microtubule- based motor orchestrates a variety of cellular processes. Recent availability of mammalian genomes has enabled analyses of kinesins on the whole genome. Here we present a novel full-length kinesin prediction program (FKPP) for mammalian kinesin gene discovery based on a comparative genomics approach. Contrary to previous predictions of 94 kinesins, we identify a total of 134 potentially kinesin genes from mammalian genomes, including 45 from mouse, 45 from rat and 44 from human. In addition, FKPP synthesizes 25 potentially full-length mammalian kinesins based on the partial sequences in the database. Surprisingly, FKPP reveals that full-length human CENP-E contains 2701 aa rather than 2663 aa in the database. Experimentation using sequence specific antibody and cDNA sequencing of human CENP-E validates the accuracy of FKPP. Given the remarkable computing efficiency and accuracy of FKPP, we reclassify the mammalian kinesin superfamily. Since current databases contain many incomplete sequences, FKPP may provide a novel approach for molecular delineation of kinesins and other protein families.

  7. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  8. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

    Directory of Open Access Journals (Sweden)

    Richard Allen White III

    2015-09-01

    Full Text Available Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacteria belonging to Alphaproteobacteria and Gammaproteobacteria were dominant in the microbialites and sediments, respectively. The microbialites were also home to many other groups associated with microbialite formation including filamentous cyanobacteria and dissimilatory sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global microbialite microbiome. Other members were present that are typically not associated with microbialites including Gemmatimonadetes and iron-oxidizing Betaproteobacteria, which participate in carbon metabolism and iron cycling. Compared to the sediments, the microbialite microbiome has significantly more genes associated with photosynthetic processes (e.g., photosystem II reaction centers, carotenoid and chlorophyll biosynthesis and carbon fixation (e.g., CO dehydrogenase. The Clinton Creek microbialite communities had strikingly similar functional potentials to non-lithifying microbial mats from the Canadian High Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes (R2 0.900. These metagenomic profiles from an anthropogenic microbialite-forming ecosystem provide context to microbialite formation on a human-relevant timescale.

  9. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

    Directory of Open Access Journals (Sweden)

    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  10. Integrative Genome-wide Analysis Reveals Cooperative Regulation of Alternative Splicing by hnRNP Proteins

    Directory of Open Access Journals (Sweden)

    Stephanie C. Huelga

    2012-02-01

    Full Text Available Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here, we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS in human cells. Using splicing-sensitive microarrays, crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq, and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and autoregulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells.

  11. Comparative Transcriptome Analysis to Reveal Genes Involved in Wheat Hybrid Necrosis

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2014-12-01

    Full Text Available Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469 were investigated using digital gene expression (DGE. A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO revealed that most of the up-regulated genes belong to “universal stress related”, “DNA/RNA binding”, “protein degradation” functional groups, while the down-regulated genes belong to “carbohydrate metabolism” and “translation regulation” functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  12. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves.

    Science.gov (United States)

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

    2016-01-01

    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves. PMID:27005614

  13. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta “Gold Standard” Leaves

    Directory of Open Access Journals (Sweden)

    Juanjuan Yu

    2016-03-01

    Full Text Available Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta “Gold Standard” is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta “Gold Standard”, as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta “Gold Standard”. For example, cytosolic glutamine synthetase (GS1, heat shock protein 70 (Hsp70, and chloroplastic elongation factor G (cpEF-G were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves.

  14. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta “Gold Standard” Leaves

    Science.gov (United States)

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

    2016-01-01

    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta “Gold Standard” is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta “Gold Standard”, as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta “Gold Standard”. For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves. PMID:27005614

  15. Service innovation management practices in the telecommunications industry: what does cross country analysis reveal?

    Science.gov (United States)

    Rahman, Syed Abidur; Taghizadeh, Seyedeh Khadijeh; Ramayah, T; Ahmad, Noor Hazlina

    2015-01-01

    Service innovation management practice is currently being widely scrutinized mainly in the developed countries, where it has been initiated. The current study attempts to propose a framework and empirically validate and explain the service innovation practices for successful performance in the telecommunications industry of two developing countries, Malaysia and Bangladesh. The research framework proposes relationships among organisational culture, operating core (innovation process, cross-functional organisation, and implementation of tools/technology), competition-informed pricing, and performance. A total of 176 usable data from both countries are analysed for the purpose of the research. The findings show that organisational culture tends to be more influential on innovation process and cross-functional organisation in Malaysian telecommunication industry. In contrast, implementation of tools/technology plays a more instrumental role in competition-informed pricing practices in Bangladesh. This study revealed few differences in the innovation management practices between two developing countries. The findings have strategic implications for the service sectors in both the developing countries regarding implementation of innovative enterprises, especially in Bangladesh where innovation is the basis for survival. Testing the innovation management practices in the developing countries perhaps contains uniqueness in the field of innovation management.

  16. Systematic transcriptome analysis reveals elevated expression of alcohol-metabolizing genes in NAFLD livers.

    Science.gov (United States)

    Zhu, Ruixin; Baker, Susan S; Moylan, Cynthia A; Abdelmalek, Manal F; Guy, Cynthia D; Zamboni, Fausto; Wu, Dingfeng; Lin, Weili; Liu, Wensheng; Baker, Robert D; Govindarajan, Sugantha; Cao, Zhiwei; Farci, Patrizia; Diehl, Anna Mae; Zhu, Lixin

    2016-03-01

    Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley © Sons, Ltd.

  17. Proteomic analysis of a segregant population reveals candidate proteins linked to mealiness in peach.

    Science.gov (United States)

    Almeida, Andréa Miyasaka; Urra, Claudio; Moraga, Carol; Jego, Marcela; Flores, Alejandra; Meisel, Lee; González, Mauricio; Infante, Rodrigo; Defilippi, Bruno G; Campos-Vargas, Reinaldo; Orellana, Ariel

    2016-01-10

    Peaches are stored at low temperatures to delay ripening and increase postharvest life. However some varieties are susceptible to chilling injury,which leads to fruit mealiness, browning and flesh bleeding. In order to identify potentialmarkers associated with chilling injury,we performed proteomic analyses on a segregating population with contrasting susceptibility to chilling-induced mealiness. Chilling-induced mealiness was assessed by measuring juiciness in fruits that have been stored in cold and then allowed to ripen. Fruitmesocarp and leaf proteome from contrasting segregants were analyzed using 2-DE gels. Comparison of protein abundance between segregants revealed 133 spots from fruit mesocarp and 36 from leaf. Thirty four fruit mesocarp proteins were identified from these spots. Most of these proteins were related to ethylene synthesis, ABA response and stress response. Leaf protein analyses identified 22 proteins, most of which related to energy metabolism. Some of the genes that code for these proteins have been previously correlated with chilling injury through transcript analyses and co-segregation with mealiness QTLs. The results from this study, further deciphers the molecular mechanisms associated with chilling response in peach fruit, and identifies candidate proteins linked to mealiness in peach which may be used as putative markers for this trait. PMID:26459401

  18. Behavioral Analysis of Dopaminergic Activation in Zebrafish and Rats Reveals Similar Phenotypes.

    Science.gov (United States)

    Ek, Fredrik; Malo, Marcus; Åberg Andersson, Madelene; Wedding, Christoffer; Kronborg, Joel; Svensson, Peder; Waters, Susanna; Petersson, Per; Olsson, Roger

    2016-05-18

    Zebrafish is emerging as a complement to mammals in behavioral studies; however, there is a lack of comparative studies with rodents and humans to establish the zebrafish as a predictive translational model. Here we present a detailed phenotype evaluation of zebrafish larvae, measuring 300-3000 variables and analyzing them using multivariate analysis to identify the most important ones for further evaluations. The dopamine agonist apomorphine has previously been shown to have a complex U-shaped dose-response relationship in the variable distance traveled. In this study, we focused on breaking down distance traveled into more detailed behavioral phenotypes for both zebrafish and rats and identified in the multivariate analysis low and high dose phenotypes with characteristic behavioral features. Further analysis of single parameters also identified an increased activity at the lowest concentration indicative of a U-shaped dose-response. Apomorphine increased the distance of each swim movement (bout) at both high and low doses, but the underlying behavior of this increase is different; at high dose, both bout duration and frequency increased whereas bout max speed was higher at low dose. Larvae also displayed differences in place preference. The low dose phenotype spent more time in the center, indicative of an anxiolytic effect, while the high-dose phenotype had a wall preference. These dose-dependent effects corroborated findings in a parallel rat study and previous observations in humans. The translational value of pharmacological zebrafish studies was further evaluated by comparing the amino acid sequence of the dopamine receptors (D1-D4), between zebrafish, rats and humans. Humans and zebrafish share 100% of the amino acids in the binding site for D1 and D3 whereas D2 and D4 receptors share 85-95%. Molecular modeling of dopamine D2 and D4 receptors indicated that nonconserved amino acids have limited influence on important ligand-receptor interactions. PMID

  19. Phylogenetic analysis of the Australian rosella parrots (Platycercus) reveals discordance among molecules and plumage.

    Science.gov (United States)

    Shipham, Ashlee; Schmidt, Daniel J; Joseph, Leo; Hughes, Jane M

    2015-10-01

    Relationships and species limits among the colourful Australian parrots known as rosellas (Platycercus) are contentious because of poorly understood patterns of parapatry, sympatry and hybridization as well as complex patterns of geographical replacement of phenotypic forms. Two subgenera are, however, conventionally recognised: Platycercus comprises the blue-cheeked crimson rosella complex (Crimson Rosella P. elegans and Green Rosella P. caledonicus), and Violania contains the remaining four currently recognised species (Pale-headed Rosella P. adscitus, Eastern Rosella P. eximius, Northern Rosella P. venustus, and Western Rosella P. icterotis). We used phylogenetic analysis of ten loci (one mitochondrial, eight autosomal and one z-linked) and several individuals per nominal species primarily to examine relationships within the subgenera, especially the relationships and species limits within Violania. Of these, P. adscitus and P. eximius have long been considered sister species or conspecific due to a morphology-based hybrid zone and an early phylogenetic analysis of mitochondrial DNA restriction fragment length polymorphisms. The multilocus phylogenetic analysis presented here supports an alternative hypothesis aligning P. adscitus and P. venustus as sister species. Using divergence rates published in other avian studies, we estimated the divergence between P. venustus and P. adscitus at 0.0148-0.6124MYA and that between the P. adscitus/P. venustus ancestor and P. eximius earlier at 0.1617-1.0816MYA, both within the Pleistocene. Discordant topologies among gene and species trees are discussed and proposed to be the result of historical gene flow and/or incomplete lineage sorting (ILS). In particular, we suggest that discordance between mitochondrial and nuclear data may be the result of asymmetrical mitochondrial introgression from P. adscitus into P. eximius. The biogeographical implications of our findings are discussed relative to similarly distributed groups

  20. Phylogenetic analysis of the Australian rosella parrots (Platycercus) reveals discordance among molecules and plumage.

    Science.gov (United States)

    Shipham, Ashlee; Schmidt, Daniel J; Joseph, Leo; Hughes, Jane M

    2015-10-01

    Relationships and species limits among the colourful Australian parrots known as rosellas (Platycercus) are contentious because of poorly understood patterns of parapatry, sympatry and hybridization as well as complex patterns of geographical replacement of phenotypic forms. Two subgenera are, however, conventionally recognised: Platycercus comprises the blue-cheeked crimson rosella complex (Crimson Rosella P. elegans and Green Rosella P. caledonicus), and Violania contains the remaining four currently recognised species (Pale-headed Rosella P. adscitus, Eastern Rosella P. eximius, Northern Rosella P. venustus, and Western Rosella P. icterotis). We used phylogenetic analysis of ten loci (one mitochondrial, eight autosomal and one z-linked) and several individuals per nominal species primarily to examine relationships within the subgenera, especially the relationships and species limits within Violania. Of these, P. adscitus and P. eximius have long been considered sister species or conspecific due to a morphology-based hybrid zone and an early phylogenetic analysis of mitochondrial DNA restriction fragment length polymorphisms. The multilocus phylogenetic analysis presented here supports an alternative hypothesis aligning P. adscitus and P. venustus as sister species. Using divergence rates published in other avian studies, we estimated the divergence between P. venustus and P. adscitus at 0.0148-0.6124MYA and that between the P. adscitus/P. venustus ancestor and P. eximius earlier at 0.1617-1.0816MYA, both within the Pleistocene. Discordant topologies among gene and species trees are discussed and proposed to be the result of historical gene flow and/or incomplete lineage sorting (ILS). In particular, we suggest that discordance between mitochondrial and nuclear data may be the result of asymmetrical mitochondrial introgression from P. adscitus into P. eximius. The biogeographical implications of our findings are discussed relative to similarly distributed groups

  1. Gene coexpression analysis reveals complex metabolism of the monoterpene alcohol linalool in Arabidopsis flowers.

    OpenAIRE

    Ginglinger, J.-F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T. G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullmann, P.; Beran, F.; Claudel, P.; Verstappen, F.; Fischer, M. J. C.; Karst, F

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus predicted to be involved in monoterpenoid metabolism. We show that all four selected genes, the two terpene synthases (TPS10 and TPS14) and the two cytochrome P450s (CYP71B31 and CYP76C3), are simu...

  2. Potential analysis reveals changing number of climate states during the last 60 kyr

    OpenAIRE

    V. N. Livina; F. Kwasniok; Lenton, T. M.

    2010-01-01

    We develop and apply a new statistical method of potential analysis for detecting the number of states of a geophysical system, from its recorded time series. Estimation of the degree of a polynomial potential allows us to derive the number of potential wells in a system. The method correctly detects changes in the number of wells in artificial data. In ice-core proxy records of Greenland paleotemperature, a reduction in the number of climate states from two to one is detected sometime prior ...

  3. The genetic structure of Oreochromis spp. (Tilapia) populations in Malaysia as revealed by microsatellite DNA analysis.

    Science.gov (United States)

    Bhassu, S; Yusoff, K; Panandam, J M; Embong, W K; Oyyan, S; Tan, S G

    2004-08-01

    The genetic make-up of five populations of Oreochromis spp. was examined by microsatellite analysis. Eleven polymorphic microsatellite loci showed significant departures from the Hardy-Weinberg equilibrium. The mean heterozygosity ranged from 0.6280 to 0.7040 for each population. The genetic distance values showed a clear separation between O. niloticus and O. mossambicus. The differentiation of the O. niloticus populations was then tested with various genetic measures, which are based on both the Infinite Allele and the Stepwise Mutation models. All these measures grouped the populations similarly. PMID:15487586

  4. Quantised transistor response to ion channels revealed by nonstationary noise analysis

    Science.gov (United States)

    Becker-Freyseng, C.; Fromherz, P.

    2011-11-01

    We report on the quantised response of a field-effect transistor to molecular ion channels in a biomembrane. HEK293-type cells overexpressing the Shaker B potassium channel were cultured on a silicon chip. An enhanced noise of the transistor is observed when the ion channels are activated. The analysis of the fluctuations in terms of binomial statistics identifies voltage quanta of about 1 μV on the gate. They are attributed to the channel currents that affect the gate voltage according to the Green's function of the cell-chip junction.

  5. Crystallization of Probucol in Nanoparticles Revealed by AFM Analysis in Aqueous Solution.

    Science.gov (United States)

    Egami, Kiichi; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-08-01

    The crystallization behavior of a pharmaceutical drug in nanoparticles was directly evaluated by atomic force microscopy (AFM) force curve measurements in aqueous solution. A ternary spray-dried sample (SPD) was prepared by spray drying the organic solvent containing probucol (PBC), hypromellose (HPMC), and sodium dodecyl sulfate (SDS). The amorphization of PBC in the ternary SPD was confirmed by powder X-ray diffraction (PXRD) and solid-state 13C NMR measurements. A nanosuspension containing quite small particles of 25 nm in size was successfully prepared immediately after dispersion of the ternary SPD into water. Furthermore, solution-state 1H NMR measurements revealed that a portion of HPMC coexisted with PBC as a mixed state in the freshly prepared nanosuspension particles. After storing the nanosuspension at 25 °C, a gradual increase in the size of the nanoparticles was observed, and the particle size changed to 93.9 nm after 7 days. AFM enabled the direct observation of the morphology and agglomeration behavior of the nanoparticles in water. Moreover, AFM force-distance curves were changed from (I) to (IV), depending on the storage period, as follows: (I) complete indentation within an applied force of 1 nN, (II) complete indentation with an applied force of 1-5 nN, (III) partial indentation with an applied force of 5 nN, and (IV) nearly no indentation with an applied force of 5 nN. This stiffness increase of the nanoparticles was attributed to gradual changes in the molecular state of PBC from the amorphous to the crystal state. Solid-state 13C NMR measurements of the freeze-dried samples demonstrated the presence of metastable PBC Form II crystals in the stored nanosuspension, strongly supporting the AFM results. PMID:26106951

  6. Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites

    Directory of Open Access Journals (Sweden)

    Sibley L David

    2005-12-01

    Full Text Available Abstract Background The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp. Results Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex, and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery. In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites. Conclusion The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility.

  7. Analysis of neurogenesis during experimental autoimmune encephalomyelitis reveals pitfalls of bioluminescence imaging.

    Science.gov (United States)

    Ayzenberg, Ilya; Schlevogt, Sibylle; Metzdorf, Judith; Stahlke, Sarah; Pedreitturia, Xiomara; Hunfeld, Anika; Couillard-Despres, Sebastien; Kleiter, Ingo

    2015-01-01

    Bioluminescence imaging is a sensitive approach for longitudinal neuroimaging. Transgenic mice expressing luciferase under the promoter of doublecortin (DCX-luc), a specific marker of neuronal progenitor cells (NPC), allow monitoring of neurogenesis in living mice. Since the extent and time course of neurogenesis during autoimmune brain inflammation are controversial, we investigated neurogenesis in MOG-peptide induced experimental allergic encephalomyelitis (EAE) using DCX-luc reporter mice. We observed a marked, 2- to 4-fold increase of the bioluminescence signal intensity 10 days after EAE induction and a gradual decline 1-2 weeks thereafter. In contrast, immunostaining for DCX revealed no differences between EAE and control mice 2 and 4 weeks after immunization in zones of adult murine neurogenesis such as the dentate gyrus. Ex vivo bioluminescence imaging showed similar luciferase expression in brain homogenates of EAE and control animals. Apart from complete immunization including MOG-peptide also incomplete immunization with complete Freund´s adjuvant and pertussis toxin resulted in a rapid increase of the in vivo bioluminescence signal. Blood-brain barrier (BBB) leakage was demonstrated 10 days after both complete and incomplete immunization and might explain the increased bioluminescence signal in vivo. We conclude, that acute autoimmune inflammation in EAE does not alter neurogenesis, at least at the stage of DCX-expressing NPC. Effects of immunization on the BBB integrity must be considered when luciferase is used as a reporter within the CNS during the active stage of EAE. Models with stable CNS-restricted luciferase expression could serve as technically convenient way to evaluate BBB integrity in a longitudinal manner.

  8. Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating.

    Science.gov (United States)

    Seitsonen, Jani J T; Shakeel, Shabih; Susi, Petri; Pandurangan, Arun P; Sinkovits, Robert S; Hyvönen, Heini; Laurinmäki, Pasi; Ylä-Pelto, Jani; Topf, Maya; Hyypiä, Timo; Butcher, Sarah J

    2012-07-01

    Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of the Enterovirus species Human enterovirus A (HEV-A) within the Picornaviridae family. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of the HEV-A species. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.

  9. Spatiotemporal molecular analysis of cyanobacteria blooms reveals Microcystis--Aphanizomenon interactions.

    Directory of Open Access Journals (Sweden)

    Todd R Miller

    Full Text Available Spatial and temporal variability in cyanobacterial community composition (CCC within and between eutrophic lakes is not well-described using culture independent molecular methods. We analyzed CCC across twelve locations in four eutrophic lakes and within-lake locations in the Yahara Watershed, WI, on a weekly basis, for 5 months. Taxa were discriminated by length of MspI-digested cpcB/A intergenic spacer gene sequences and identified by comparison to a PCR-based clone library. CCC across all stations was spatially segregated by depth of sampling locations (ANOSIM R = 0.23, p < 0.001. Accordingly, CCC was correlated with thermal stratification, nitrate and soluble reactive phosphorus (SRP, R = 0.2-0.3. Spatial variability in CCC and temporal trends in taxa abundances were rarely correlative between sampling locations in the same lake indicating significant within lake spatiotemporal heterogeneity. Across all stations, a total of 37 bloom events were observed based on distinct increases in phycocyanin. Out of 97 taxa, a single Microcystis, and two different Aphanizomenon taxa were the dominant cyanobacteria detected during bloom events. The Microcystis and Aphanizomenon taxa rarely bloomed together and were significantly anti-correlated with each other at 9 of 12 stations with Pearson R values of -0.6 to -0.9 (p < 0.001. Of all environmental variables measured, nutrients, especially nitrate were significantly greater during periods of Aphanizomenon dominance while the nitrate+nitrite:SRP ratio was lower. This study shows significant spatial variability in CCC within and between lakes structured by depth of the sampling location. Furthermore, our study reveals specific genotypes involved in bloom formation. More in-depth characterization of these genotypes should lead to a better understanding of factors promoting bloom events in these lakes and more reliable bloom prediction models.

  10. Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal oscillation of central metabolic processes

    Energy Technology Data Exchange (ETDEWEB)

    Stockel, Jana; Welsh, Eric A.; Liberton, Michelle L.; Kunnavakkam, Rangesh V.; Aurora, Rajeev; Pakrasi, Himadri B.

    2008-04-22

    Cyanobacteria are oxygenic photosynthetic organisms, and the only prokaryotes known to have a circadian cycle. Unicellular diazotrophic cyanobacteria such as Cyanothece 51142 can fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. Thus, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of two processes: photosynthesis during the day, and nitrogen fixation at night. While previous studies have examined periodic changes transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5000 genes in Cyanothece 51142 during two consecutive diurnal periods. We found that ~30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes in numerous individual pathways, such as glycolysis, pentose phosphate pathway and glycogen metabolism, were co-regulated and maximally expressed at distinct phases during the diurnal cycle. Our analyses suggest that the demands of nitrogen fixation greatly influence major metabolic activities inside Cyanothece cells and thus drive various cellular activities. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium

  11. Crystallization of Probucol in Nanoparticles Revealed by AFM Analysis in Aqueous Solution.

    Science.gov (United States)

    Egami, Kiichi; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-08-01

    The crystallization behavior of a pharmaceutical drug in nanoparticles was directly evaluated by atomic force microscopy (AFM) force curve measurements in aqueous solution. A ternary spray-dried sample (SPD) was prepared by spray drying the organic solvent containing probucol (PBC), hypromellose (HPMC), and sodium dodecyl sulfate (SDS). The amorphization of PBC in the ternary SPD was confirmed by powder X-ray diffraction (PXRD) and solid-state 13C NMR measurements. A nanosuspension containing quite small particles of 25 nm in size was successfully prepared immediately after dispersion of the ternary SPD into water. Furthermore, solution-state 1H NMR measurements revealed that a portion of HPMC coexisted with PBC as a mixed state in the freshly prepared nanosuspension particles. After storing the nanosuspension at 25 °C, a gradual increase in the size of the nanoparticles was observed, and the particle size changed to 93.9 nm after 7 days. AFM enabled the direct observation of the morphology and agglomeration behavior of the nanoparticles in water. Moreover, AFM force-distance curves were changed from (I) to (IV), depending on the storage period, as follows: (I) complete indentation within an applied force of 1 nN, (II) complete indentation with an applied force of 1-5 nN, (III) partial indentation with an applied force of 5 nN, and (IV) nearly no indentation with an applied force of 5 nN. This stiffness increase of the nanoparticles was attributed to gradual changes in the molecular state of PBC from the amorphous to the crystal state. Solid-state 13C NMR measurements of the freeze-dried samples demonstrated the presence of metastable PBC Form II crystals in the stored nanosuspension, strongly supporting the AFM results.

  12. Rangewide genetic analysis of Lesser Prairie-Chicken reveals population structure, range expansion, and possible introgression

    Science.gov (United States)

    Oyler-McCance, Sara J.; DeYoung, Randall W; Fike, Jennifer; Hagen, Christian A.; Johnson, Jeff A.; Larsson, Lena C; Patten, Michael

    2016-01-01

    The distribution of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) has been markedly reduced due to loss and fragmentation of habitat. Portions of the historical range, however, have been recolonized and even expanded due to planting of conservation reserve program (CRP) fields that provide favorable vegetation structure for Lesser Prairie-Chickens. The source population(s) feeding the range expansion is unknown, yet has resulted in overlap between Lesser and Greater Prairie-Chickens (T. cupido) increasing the potential for hybridization. Our objectives were to characterize connectivity and genetic diversity among populations, identify source population(s) of recent range expansion, and examine hybridization with the Greater Prairie-Chicken. We analyzed 640 samples from across the range using 13 microsatellites. We identified three to four populations corresponding largely to ecoregions. The Shinnery Oak Prairie and Sand Sagebrush Prairie represented genetically distinct populations (F ST > 0.034 and F ST > 0.023 respectively). The Shortgrass/CRP Mosaic and Mixed Grass ecoregions appeared admixed (F ST = 0.009). Genetic diversity was similar among ecoregions and N e ranged from 142 (95 % CI 99–236) for the Shortgrass/CRP Mosaic to 296 (95 % CI 233–396) in the Mixed Grass Prairie. No recent migration was detected among ecoregions, except asymmetric dispersal from both the Mixed Grass Prairie and to a lesser extent the Sand Sagebrush Prairie north into adjacent Shortgrass/CRP Mosaic (m = 0.207, 95 % CI 0.116–0.298, m = 0.097, 95 % CI 0.010–0.183, respectively). Indices investigating potential hybridization in the Shortgrass/CRP Mosaic revealed that six of the 13 individuals with hybrid phenotypes were significantly admixed suggesting hybridization. Continued monitoring of diversity within and among ecoregions is warranted as are actions promoting genetic connectivity and range expansion.

  13. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

    Science.gov (United States)

    MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

    2011-01-01

    Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  14. Analysis of genome sequences from plant pathogenic Rhodococcus reveals genetic novelties in virulence loci.

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    Allison L Creason

    Full Text Available Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of three loci present on a linear plasmid, with the fas operon central to virulence. The Fas proteins synthesize, modify, and activate a mixture of growth regulating cytokinins, which cause a hormonal imbalance in plants, resulting in abnormal growth. We sequenced and compared the genomes of 20 isolates of Rhodococcus to gain insights into the mechanisms and evolution of virulence in these bacteria. Horizontal gene transfer was identified as critical but limited in the scale of virulence evolution, as few loci are conserved and exclusive to phytopathogenic isolates. Although the fas operon is present in most phytopathogenic isolates, it is absent from phytopathogenic isolate A21d2. Instead, this isolate has a horizontally acquired gene chimera that encodes a novel fusion protein with isopentyltransferase and phosphoribohydrolase domains, predicted to be capable of catalyzing and activating cytokinins, respectively. Cytokinin profiling of the archetypal D188 isolate revealed only one activate cytokinin type that was specifically synthesized in a fas-dependent manner. These results suggest that only the isopentenyladenine cytokinin type is synthesized and necessary for Rhodococcus phytopathogenicity, which is not consistent with the extant model stating that a mixture of cytokinins is necessary for Rhodococcus to cause leafy gall symptoms. In all, data indicate that only four horizontally acquired functions are sufficient to confer the trait of phytopathogenicity to members of the genetically diverse clade of Rhodococcus.

  15. The integrated analysis of metabolic and protein interaction networks reveals novel molecular organizing principles

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    Walther Dirk

    2008-11-01

    Full Text Available Abstract Background The study of biological interaction networks is a central theme of systems biology. Here, we investigate the relationships between two distinct types of interaction networks: the metabolic pathway map and the protein-protein interaction network (PIN. It has long been established that successive enzymatic steps are often catalyzed by physically interacting proteins forming permanent or transient multi-enzymes complexes. Inspecting high-throughput PIN data, it was shown recently that, indeed, enzymes involved in successive reactions are generally more likely to interact than other protein pairs. In our study, we expanded this line of research to include comparisons of the underlying respective network topologies as well as to investigate whether the spatial organization of enzyme interactions correlates with metabolic efficiency. Results Analyzing yeast data, we detected long-range correlations between shortest paths between proteins in both network types suggesting a mutual correspondence of both network architectures. We discovered that the organizing principles of physical interactions between metabolic enzymes differ from the general PIN of all proteins. While physical interactions between proteins are generally dissortative, enzyme interactions were observed to be assortative. Thus, enzymes frequently interact with other enzymes of similar rather than different degree. Enzymes carrying high flux loads are more likely to physically interact than enzymes with lower metabolic throughput. In particular, enzymes associated with catabolic pathways as well as enzymes involved in the biosynthesis of complex molecules were found to exhibit high degrees of physical clustering. Single proteins were identified that connect major components of the cellular metabolism and may thus be essential for the structural integrity of several biosynthetic systems. Conclusion Our results reveal topological equivalences between the protein

  16. New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa.

    Directory of Open Access Journals (Sweden)

    Edoardo Giacopuzzi

    Full Text Available Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis, early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals. We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may

  17. Metagenomic analysis of a Mexican ripened cheese reveals a unique complex microbiota.

    Science.gov (United States)

    Escobar-Zepeda, Alejandra; Sanchez-Flores, Alejandro; Quirasco Baruch, Maricarmen

    2016-08-01

    Cotija cheese is a Mexican handcrafted product made from raw cow milk whose ripening process occurs spontaneously and, presumably, it is influenced by environmental conditions. Its sensory characteristics and safety are probably the result of the balance between microbial populations and their metabolic capacity. In this work, we studied the dominance and richness of the bacteria in the Cotija cheese microbiome, as well as their metabolic potential by high-throughput sequencing. By the analysis of 16S ribosomal sequences, it was found that this metagenome is composed mainly of three dominant genera: Lactobacillus, Leuconostoc and Weissella, and more than 500 of non-dominant genera grouped in 31 phyla of both bacteria and archaea. The analysis of single-copy marker genes reported a similar result for dominant genera, although with greater resolution that reached the species level. Pathogenic bacteria such as Salmonella, Listeria monocytogenes, Brucella or Mycobacterium were not found. The Cotija cheese microbiome has the metabolic capacity for the synthesis of a wide range of flavor compounds, mainly involved with the metabolism of branched chain amino acids and free fatty acids. Genes associated with bacteriocin production and immunity were also found. Arguably, this is one of the most diverse metagenomes among the microbial communities related to fermented products.

  18. A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a

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    Ying Tianyi

    2010-06-01

    Full Text Available Abstract Background Shigella flexneri is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of S. flexneri have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of S. flexneri, we performed differential in-gel electrophoresis (DIGE analysis to measure changes in the expression profile that are induced by a temperature increase. Results The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains. Conclusion Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.

  19. DNA Barcode Analysis of Thrips (Thysanoptera Diversity in Pakistan Reveals Cryptic Species Complexes.

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    Romana Iftikhar

    Full Text Available Although thrips are globally important crop pests and vectors of viral disease, species identifications are difficult because of their small size and inconspicuous morphological differences. Sequence variation in the mitochondrial COI-5' (DNA barcode region has proven effective for the identification of species in many groups of insect pests. We analyzed barcode sequence variation among 471 thrips from various plant hosts in north-central Pakistan. The Barcode Index Number (BIN system assigned these sequences to 55 BINs, while the Automatic Barcode Gap Discovery detected 56 partitions, a count that coincided with the number of monophyletic lineages recognized by Neighbor-Joining analysis and Bayesian inference. Congeneric species showed an average of 19% sequence divergence (range = 5.6% - 27% at COI, while intraspecific distances averaged 0.6% (range = 0.0% - 7.6%. BIN analysis suggested that all intraspecific divergence >3.0% actually involved a species complex. In fact, sequences for three major pest species (Haplothrips reuteri, Thrips palmi, Thrips tabaci, and one predatory thrips (Aeolothrips intermedius showed deep intraspecific divergences, providing evidence that each is a cryptic species complex. The study compiles the first barcode reference library for the thrips of Pakistan, and examines global haplotype diversity in four important pest thrips.

  20. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.

    Science.gov (United States)

    Umezu, K; Sugawara, N; Chen, C; Haber, J E; Kolodner, R D

    1998-03-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10(4) to 10(5) times increased sensitivity to these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO-induced double-strand break at MAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages.

  1. Gene expression analysis reveals a gene set discriminatory to different metals in soil.

    Science.gov (United States)

    Nota, Benjamin; Verweij, Rudo A; Molenaar, Douwe; Ylstra, Bauke; van Straalen, Nico M; Roelofs, Dick

    2010-05-01

    Environmental pollution is a worldwide problem, and metals are the largest group of contaminants in soil. Microarray toxicogenomic studies with ecologically relevant organisms, such as springtails, supplement traditional ecotoxicological research but are presently rather descriptive. Classifier analysis, a more analytical application of the microarray technique, is able to predict biological classes of unknown samples. We used the uncorrelated shrunken centroid method to classify gene expression profiles of the springtail Folsomia candida exposed to soil spiked with six different metals (barium, cadmium, cobalt, chromium, lead, and zinc). We identified a gene set (classifier) of 188 genes that can discriminate between six different metals present in soil, which allowed us to predict the correct classes for samples of an independent test set with an accuracy of 83% (error rate = 0.17). This study shows further that in order to apply classifier analysis to actual contaminated field soil samples, more insight and information is needed on the transcriptional responses of soil organisms to different soil types (properties) and mixtures of contaminants. PMID:20133373

  2. Transcriptome analysis reveals candidate genes involved in luciferin metabolism in Luciola aquatilis (Coleoptera: Lampyridae)

    Science.gov (United States)

    Vongsangnak, Wanwipa; Chumnanpuen, Pramote

    2016-01-01

    Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system. PMID:27761329

  3. Time-series metagenomic analysis reveals robustness of soil microbiome against chemical disturbance.

    Science.gov (United States)

    Kato, Hiromi; Mori, Hiroshi; Maruyama, Fumito; Toyoda, Atsushi; Oshima, Kenshiro; Endo, Ryo; Fuchu, Genki; Miyakoshi, Masatoshi; Dozono, Ayumi; Ohtsubo, Yoshiyuki; Nagata, Yuji; Hattori, Masahira; Fujiyama, Asao; Kurokawa, Ken; Tsuda, Masataka

    2015-12-01

    Soil microbial communities have great potential for bioremediation of recalcitrant aromatic compounds. However, it is unclear which taxa and genes in the communities, and how they contribute to the bioremediation in the polluted soils. To get clues about this fundamental question here, time-course (up to 24 weeks) metagenomic analysis of microbial community in a closed soil microcosm artificially polluted with four aromatic compounds, including phenanthrene, was conducted to investigate the changes in the community structures and gene pools. The pollution led to drastic changes in the community structures and the gene sets for pollutant degradation. Complete degradation of phenanthrene was strongly suggested to occur by the syntrophic metabolism by Mycobacterium and the most proliferating genus, Burkholderia. The community structure at Week 24 (∼12 weeks after disappearance of the pollutants) returned to the structure similar to that before pollution. Our time-course metagenomic analysis of phage genes strongly suggested the involvement of the 'kill-the-winner' phenomenon (i.e. phage predation of Burkholderia cells) for the returning of the microbial community structure. The pollution resulted in a decrease in taxonomic diversity and a drastic increase in diversity of gene pools in the communities, showing the functional redundancy and robustness of the communities against chemical disturbance.

  4. Metagenomic analysis of a Mexican ripened cheese reveals a unique complex microbiota.

    Science.gov (United States)

    Escobar-Zepeda, Alejandra; Sanchez-Flores, Alejandro; Quirasco Baruch, Maricarmen

    2016-08-01

    Cotija cheese is a Mexican handcrafted product made from raw cow milk whose ripening process occurs spontaneously and, presumably, it is influenced by environmental conditions. Its sensory characteristics and safety are probably the result of the balance between microbial populations and their metabolic capacity. In this work, we studied the dominance and richness of the bacteria in the Cotija cheese microbiome, as well as their metabolic potential by high-throughput sequencing. By the analysis of 16S ribosomal sequences, it was found that this metagenome is composed mainly of three dominant genera: Lactobacillus, Leuconostoc and Weissella, and more than 500 of non-dominant genera grouped in 31 phyla of both bacteria and archaea. The analysis of single-copy marker genes reported a similar result for dominant genera, although with greater resolution that reached the species level. Pathogenic bacteria such as Salmonella, Listeria monocytogenes, Brucella or Mycobacterium were not found. The Cotija cheese microbiome has the metabolic capacity for the synthesis of a wide range of flavor compounds, mainly involved with the metabolism of branched chain amino acids and free fatty acids. Genes associated with bacteriocin production and immunity were also found. Arguably, this is one of the most diverse metagenomes among the microbial communities related to fermented products. PMID:27052710

  5. Eating or meeting? Cluster analysis reveals intricacies of white shark (Carcharodon carcharias) migration and offshore behavior.

    Science.gov (United States)

    Jorgensen, Salvador J; Arnoldi, Natalie S; Estess, Ethan E; Chapple, Taylor K; Rückert, Martin; Anderson, Scot D; Block, Barbara A

    2012-01-01

    Elucidating how mobile ocean predators utilize the pelagic environment is vital to understanding the dynamics of oceanic species and ecosystems. Pop-up archival transmitting (PAT) tags have emerged as an important tool to describe animal migrations in oceanic environments where direct observation is not feasible. Available PAT tag data, however, are for the most part limited to geographic position, swimming depth and environmental temperature, making effective behavioral observation challenging. However, novel analysis approaches have the potential to extend the interpretive power of these limited observations. Here we developed an approach based on clustering analysis of PAT daily time-at-depth histogram records to distinguish behavioral modes in white sharks (Carcharodon carcharias). We found four dominant and distinctive behavioral clusters matching previously described behavioral patterns, including two distinctive offshore diving modes. Once validated, we mapped behavior mode occurrence in space and time. Our results demonstrate spatial, temporal and sex-based structure in the diving behavior of white sharks in the northeastern Pacific previously unrecognized including behavioral and migratory patterns resembling those of species with lek mating systems. We discuss our findings, in combination with available life history and environmental data, and propose specific testable hypotheses to distinguish between mating and foraging in northeastern Pacific white sharks that can provide a framework for future work. Our methodology can be applied to similar datasets from other species to further define behaviors during unobservable phases. PMID:23144707

  6. Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants

    Science.gov (United States)

    Greenwood, Edward JD; Matheson, Nicholas J; Wals, Kim; van den Boomen, Dick JH; Antrobus, Robin; Williamson, James C; Lehner, Paul J

    2016-01-01

    Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function. DOI: http://dx.doi.org/10.7554/eLife.18296.001 PMID:27690223

  7. ANALYSIS OF FACTORS INFLUENCING TRAVEL CONSUMER SATISFACTION AS REVEALED BY ONLINE COMMUNICATION PLATFORMS

    Directory of Open Access Journals (Sweden)

    Olimpia I. BAN

    2016-08-01

    Full Text Available The objective of the present empirical study is to determine the factors influencing the tourism consumer satisfaction, as it results from the evaluations posted on virtual platforms. The communication platform chosen as study is the Romanian website Amfostacolo.ro. In this case, the travel consumer satisfaction is expressed by the score of the ratings posted on the virtual platform Amfostacolo.ro and the decision to recommend or not the unit / destination. Considering the peculiarities of the communication platform studied, the elements influencing the score indicating satisfaction there can be identified as components of tourism supply and the characteristics of the reviewer. Data processing has been carried out with ordinary least squares (OLS, structural equation modeling (confirmatory factor analysis, path analysis, cluster analisys and polytomous logistic regression. The results broadly confirm the hypotheses, namely that: the type of stay and the age of the reviewer influence the satisfaction of the consumer more than the destination and number of stars of the accommodation, the age group of the reviewer influences the destination yet it is uncertain about the influence of the variables related to the holiday (the type of stay and the number of stars of the accommodation, the meal service influences more than other attributes the consumer satisfaction and the recommendation of the reviewer is influenced by the characteristics related to his person and the holiday consumed.

  8. Uncoating Mechanism of Carnation Mottle Virus Revealed by Cryo-EM Single Particle Analysis.

    Science.gov (United States)

    Wang, Chun-Yan; Zhang, Qin-Fen; Gao, Yuan-Zhu; Xie, Li; Li, Hong-Mei; Hong, Jian; Zhang, Chuan-Xi

    2015-01-01

    Genome uncoating is a prerequisite for the successful infection of plant viruses in host plants. Thus far, little is known about the genome uncoating of the Carnation mottle virus (CarMV). Here, we obtained two reconstructions of CarMV at pH7 in the presence (Ca-pH7) and absence (EDTA-pH7) of calcium ions by Cryo-EM single particle analysis, which achieved 6.4 Å and 8 Å resolutions respectively. Our results showed that chelation of the calcium ions under EDTA-pH7 resulted in reduced interaction between the subunits near the center of the asymmetric unit but not overall size change of the viral particles, which indicated that the role of the calcium ions in CarMV was not predominantly for the structural preservation. Part of the genomic RNA closest to the capsid was found to be located near the center of the asymmetric unit, which might result from the interaction between genomic RNA and Lys194 residues. Together with the electrostatic potential analysis on the inner surface of the asymmetric unit, the reduced interaction near the center of the asymmetric unit under EDTA-pH7 suggested that the genome release of CarMV might be realized through the center of the asymmetric unit.

  9. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes.

    Science.gov (United States)

    Paraboschi, Elvezia Maria; Cardamone, Giulia; Rimoldi, Valeria; Gemmati, Donato; Spreafico, Marta; Duga, Stefano; Soldà, Giulia; Asselta, Rosanna

    2015-09-30

    Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  10. Transcriptome and Metabolite analysis reveal candidate genes of the cardiac glycoside biosynthetic pathway from Calotropis procera

    Science.gov (United States)

    Pandey, Akansha; Swarnkar, Vishakha; Pandey, Tushar; Srivastava, Piush; Kanojiya, Sanjeev; Mishra, Dipak Kumar; Tripathi, Vineeta

    2016-01-01

    Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG’s were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair. Around 66.6% of unigenes were annotated by using various public databases and 5324 unigenes showed significant match in the KEGG database involved in 133 different pathways of plant metabolism. Further KEGG analysis resulted in identification of 336 unigenes involved in cardenolide biosynthesis. Tissue specific expression analysis of 30 putative transcripts involved in terpenoid, steroid and cardenolide pathways showed a positive correlation between metabolite and transcript accumulation. Wound stress elevated CG levels as well the levels of the putative transcripts involved in its biosynthetic pathways. This result further validated the involvement of identified transcripts in CGs biosynthesis. The identified transcripts will lay a substantial foundation for further research on metabolic engineering and regulation of cardiac glycosides biosynthesis pathway genes. PMID:27703261

  11. Failure analysis of porcupine quills under axial compression reveals their mechanical response during buckling.

    Science.gov (United States)

    Torres, Fernando G; Troncoso, Omar P; Diaz, John; Arce, Diego

    2014-11-01

    Porcupine quills are natural structures formed by a thin walled conical shell and an inner foam core. Axial compression tests, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR) were all used to compare the characteristics and mechanical properties of porcupine quills with and without core. The failure mechanisms that occur during buckling were analyzed by scanning electron microscopy (SEM), and it was found that delamination buckling is mostly responsible for the decrease in the measured buckling stress of the quills with regard to predicted theoretical values. Our analysis also confirmed that the foam core works as an energy dissipater improving the mechanical response of an empty cylindrical shell, retarding the onset of buckling as well as producing a step wise decrease in force after buckling, instead of an instantaneous decrease in force typical for specimens without core. Cell collapse and cell densification in the inner foam core were identified as the key mechanisms that allow for energy absorption during buckling.

  12. Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

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    Biecek Przemysław

    2011-06-01

    Full Text Available Abstract Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

  13. Eating or meeting? Cluster analysis reveals intricacies of white shark (Carcharodon carcharias migration and offshore behavior.

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    Salvador J Jorgensen

    Full Text Available Elucidating how mobile ocean predators utilize the pelagic environment is vital to understanding the dynamics of oceanic species and ecosystems. Pop-up archival transmitting (PAT tags have emerged as an important tool to describe animal migrations in oceanic environments where direct observation is not feasible. Available PAT tag data, however, are for the most part limited to geographic position, swimming depth and environmental temperature, making effective behavioral observation challenging. However, novel analysis approaches have the potential to extend the interpretive power of these limited observations. Here we developed an approach based on clustering analysis of PAT daily time-at-depth histogram records to distinguish behavioral modes in white sharks (Carcharodon carcharias. We found four dominant and distinctive behavioral clusters matching previously described behavioral patterns, including two distinctive offshore diving modes. Once validated, we mapped behavior mode occurrence in space and time. Our results demonstrate spatial, temporal and sex-based structure in the diving behavior of white sharks in the northeastern Pacific previously unrecognized including behavioral and migratory patterns resembling those of species with lek mating systems. We discuss our findings, in combination with available life history and environmental data, and propose specific testable hypotheses to distinguish between mating and foraging in northeastern Pacific white sharks that can provide a framework for future work. Our methodology can be applied to similar datasets from other species to further define behaviors during unobservable phases.

  14. Transcriptome Analysis Reveals Putative Genes Involved in Iridoid Biosynthesis in Rehmannia glutinosa

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    Xianen Li

    2012-10-01

    Full Text Available Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R. glutinosa and investigate genes involved in iridoid biosynthesis, we used massively parallel pyrosequencing on the 454 GS FLX Titanium platform to generate a substantial EST dataset. Based on sequence similarity searches against the public sequence databases, the sequences were first annotated and then subjected to Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG based analysis. Bioinformatic analysis indicated that the 454 assembly contained a set of genes putatively involved in iridoid biosynthesis. Significantly, homologues of the secoiridoid pathway genes that were only identified in terpenoid indole alkaloid producing plants were also identified, whose presence implied that route II iridoids and route I iridoids share common enzyme steps in the early stage of biosynthesis. The gene expression patterns of four prenyltransferase transcripts were analyzed using qRT-PCR, which shed light on their putative functions in tissues of R. glutinosa. The data explored in this study will provide valuable information for further studies concerning iridoid biosynthesis.

  15. Quantitative proteomic analysis of mice corneal tissues reveals angiogenesis-related proteins involved in corneal neovascularization.

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    Shen, Minqian; Tao, Yimin; Feng, Yifan; Liu, Xing; Yuan, Fei; Zhou, Hu

    2016-07-01

    Corneal neovascularization (CNV) was induced in Balb/c mice by alkali burns in the central area of the cornea with a diameter of 2.5mm. After fourteen days, the cornea from one eye was collected for histological staining for CNV examination, while the cornea from the other eye of the same mouse was harvested for proteomic analysis. The label-free quantitative proteomic approach was applied to analyze five normal corneal tissues (normal group mice n=5) and five corresponding neovascularized corneal tissues (model group mice n=5). A total of 2124 proteins were identified, and 1682 proteins were quantified from these corneal tissues. Among these quantified proteins, 290 proteins were significantly changed between normal and alkali burned corneal tissues. Of these significantly changed proteins, 35 were reported or predicted as angiogenesis-related proteins. Then, these 35 proteins were analyzed using Ingenuity Pathway Analysis Software, resulting in 26 proteins enriched and connected to each other in the protein-protein interaction network, such as Lcn-2, αB-crystallin and Serpinf1 (PEDF). These three significantly changed proteins were selected for further Western blotting validation. Consistent with the quantitative proteomic results, Western blotting showed that Lcn-2 and αB-crystallin were significantly up-regulated in CNV model, while PEDF was down-regulated. This study provided increased understanding of angiogenesis-related proteins involved in corneal vascular development, which will be useful in the ophthalmic clinic of specifically target angiogenesis.

  16. Regional movement patterns of a small-bodied shark revealed by stable-isotope analysis.

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    Munroe, S E M; Heupel, M R; Fisk, A T; Logan, M; Simpfendorfer, C A

    2015-05-01

    This study used stable-isotope analysis to define the nearshore regional residency and movements of the small-bodied Australian sharpnose shark Rhizoprionodon taylori. Plasma and muscle δ(13) C and δ(15) N of R. taylori were collected from across five embayments and compared with values of seagrass and plankton from each bay. Linear distances between adjacent bays ranged from 30 to 150 km. There was a positive geographic correlation between R. taylori tissue and environmental δ(13) C values. Populations with the highest tissue δ(15) N were collected from bays that had the highest environmental δ(15) N values. These results suggest that R. taylori did not forage more than 100 km away from their capture location within 6 months to 1 year. The successful application of isotope analysis to define R. taylori movement demonstrates that this technique may be used in addition to traditional methods to study the movement of sharks, even within similar habitats across regionally small spatial scales (<100 km). PMID:25846994

  17. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    International Nuclear Information System (INIS)

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 104 to 105 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

  18. Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population

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    Cogliati, Massimo; Zani, Alberto; Rickerts, Volker; McCormick, Ilka; Desnos-Ollivier, Marie; Velegraki, Aristea; Escandon, Patricia; Ichikawa, Tomoe; Ikeda, Reiko; Bienvenue, Anne-Lise; Tintelnot, Kathrin; Tore, Okan; Akcaglar, Sevim; Lockhart, Shawn; Tortorano, Anna Maria; Varma, Ashok

    2016-01-01

    Cryptococcus neoformans var. neoformans (serotype D) represents about 30% of the clinical isolates in Europe and is present less frequently in the other continents. It is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. Very little is known about the genotypic diversity of this Cryptococcus subtype. The aim of this study was to investigate the genotypic diversity among a set of clinical and environmental C. neoformans var. neoformans isolates and to evaluate the relationship between genotypes, geographical origin and clinical manifestations. A total of 83 globally collected C. neoformans var. neoformans isolates from Italy, Germany, France, Belgium, Denmark, Greece, Turkey, Thailand, Japan, Colombia, and the USA, recovered from different sources (primary and secondary cutaneous cryptococcosis, disseminated cryptococcosis, the environment, and animals), were included in the study. All isolates were confirmed to belong to genotype VNIV by molecular typing and they were further investigated by MLST analysis. Maximum likelihood phylogenetic as well as network analysis strongly suggested the existence of a recombinant rather than a clonal population structure. Geographical origin and source of isolation were not correlated with a specific MLST genotype. The comparison with a set of outgroup C. neoformans var. grubii isolates provided clear evidence that the two varieties have different population structures. PMID:26768709

  19. Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

    Science.gov (United States)

    Hwang, Hyundoo; Barnes, Dawn E.; Matsunaga, Yohei; Benian, Guy M.; Ono, Shoichiro; Lu, Hang

    2016-01-01

    The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

  20. Genome Wide Association Analysis Reveals New Production Trait Genes in a Male Duroc Population.

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    Kejun Wang

    Full Text Available In this study, 796 male Duroc pigs were used to identify genomic regions controlling growth traits. Three production traits were studied: food conversion ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome-wide single nucleotide polymorphism trait associations. The Gene ontology analysis identified 14 candidate genes close to significant single nucleotide polymorphisms, with growth-related functions: six for days to 100 KG (WT1, FBXO3, DOCK7, PPP3CA, AGPAT9, and NKX6-1, seven for food conversion ratio (MAP2, TBX15, IVL, ARL15, CPS1, VWC2L, and VAV3, and one for average daily gain (COL27A1. Gene ontology analysis indicated that most of the candidate genes are involved in muscle, fat, bone or nervous system development, nutrient absorption, and metabolism, which are all either directly or indirectly related to growth traits in pigs. Additionally, we found four haplotype blocks composed of suggestive single nucleotide polymorphisms located in the growth trait-related quantitative trait loci and further narrowed down the ranges, the largest of which decreased by ~60 Mb. Hence, our results could be used to improve pig production traits by increasing the frequency of favorable alleles via artificial selection.

  1. Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity.

    Science.gov (United States)

    Favela, Luis H; Coey, Charles A; Griff, Edwin R; Richardson, Michael J

    2016-07-28

    The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. PMID:27189719

  2. DNA Barcode Analysis of Thrips (Thysanoptera) Diversity in Pakistan Reveals Cryptic Species Complexes.

    Science.gov (United States)

    Iftikhar, Romana; Ashfaq, Muhammad; Rasool, Akhtar; Hebert, Paul D N

    2016-01-01

    Although thrips are globally important crop pests and vectors of viral disease, species identifications are difficult because of their small size and inconspicuous morphological differences. Sequence variation in the mitochondrial COI-5' (DNA barcode) region has proven effective for the identification of species in many groups of insect pests. We analyzed barcode sequence variation among 471 thrips from various plant hosts in north-central Pakistan. The Barcode Index Number (BIN) system assigned these sequences to 55 BINs, while the Automatic Barcode Gap Discovery detected 56 partitions, a count that coincided with the number of monophyletic lineages recognized by Neighbor-Joining analysis and Bayesian inference. Congeneric species showed an average of 19% sequence divergence (range = 5.6% - 27%) at COI, while intraspecific distances averaged 0.6% (range = 0.0% - 7.6%). BIN analysis suggested that all intraspecific divergence >3.0% actually involved a species complex. In fact, sequences for three major pest species (Haplothrips reuteri, Thrips palmi, Thrips tabaci), and one predatory thrips (Aeolothrips intermedius) showed deep intraspecific divergences, providing evidence that each is a cryptic species complex. The study compiles the first barcode reference library for the thrips of Pakistan, and examines global haplotype diversity in four important pest thrips. PMID:26741134

  3. Genetic analysis reveals demographic fragmentation of grizzly bears yielding vulnerably small populations.

    Science.gov (United States)

    Proctor, Michael F; McLellan, Bruce N; Strobeck, Curtis; Barclay, Robert M R

    2005-11-22

    Ecosystem conservation requires the presence of native carnivores, yet in North America, the distributions of many larger carnivores have contracted. Large carnivores live at low densities and require large areas to thrive at the population level. Therefore, if human-dominated landscapes fragment remaining carnivore populations, small and demographically vulnerable populations may result. Grizzly bear range contraction in the conterminous USA has left four fragmented populations, three of which remain along the Canada-USA border. A tenet of grizzly bear conservation is that the viability of these populations requires demographic linkage (i.e. inter-population movement of both sexes) to Canadian bears. Using individual-based genetic analysis, our results suggest this demographic connection has been severed across their entire range in southern Canada by a highway and associated settlements, limiting female and reducing male movement. Two resulting populations are vulnerably small (bear populations may be more threatened than previously thought and that conservation efforts must expand to include international connectivity management. They also demonstrate the ability of genetic analysis to detect gender-specific demographic population fragmentation in recently disturbed systems, a traditionally intractable yet increasingly important ecological measurement worldwide.

  4. Comparative mitochondrial genome analysis reveals the evolutionary rearrangement mechanism in Brassica.

    Science.gov (United States)

    Yang, J; Liu, G; Zhao, N; Chen, S; Liu, D; Ma, W; Hu, Z; Zhang, M

    2016-05-01

    The genus Brassica has many species that are important for oil, vegetable and other food products. Three mitochondrial genome types (mitotype) originated from its common ancestor. In this paper, a B. nigra mitochondrial main circle genome with 232,407 bp was generated through de novo assembly. Synteny analysis showed that the mitochondrial genomes of B. rapa and B. oleracea had a better syntenic relationship than B. nigra. Principal components analysis and development of a phylogenetic tree indicated maternal ancestors of three allotetraploid species in Us triangle of Brassica. Diversified mitotypes were found in allotetraploid B. napus, in which napus-type B. napus was derived from B. oleracea, while polima-type B. napus was inherited from B. rapa. In addition, the mitochondrial genome of napus-type B. napus was closer to botrytis-type than capitata-type B. oleracea. The sub-stoichiometric shifting of several mitochondrial genes suggested that mitochondrial genome rearrangement underwent evolutionary selection during domestication and/or plant breeding. Our findings clarify the role of diploid species in the maternal origin of allotetraploid species in Brassica and suggest the possibility of breeding selection of the mitochondrial genome. PMID:27079962

  5. Molecular phylogenetic analysis reveals the new genus Hemisphaericaspora of the family Debaryomycetaceae.

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    Fengli Hui

    Full Text Available Four strains of a novel ascomycetous yeast species were recovered from the frass of wood-boring beetles collected from the Baotianman Nature Reserve and the Laojieling Nature Reserve in Henan Province, China. This species produced unconjugated and deliquescent asci with hemispheroid or helmet-shaped ascospores. Analysis of gene sequences for the D1/D2 domain of the large subunit (LSU rRNA, as well as analysis of concatenated gene sequences for the nearly complete small subunit (SSU rRNA and D1/D2 domain of the large subunit (LSU rRNA placed the novel species in a small clade including only one recognised species, Candida insectamans, in the family Debaryomycetaceae (Saccharomycotina, Ascomycota. DNA sequence analyses demonstrated that the novel species was distinct from all currently recognised teleomorphic yeast genus. The name Hemisphaericaspora nanyangensis gen nov., sp. nov. is proposed to accommodate the novel genus and species. The new genus can be distinguished from closely related teleomorphic genera Lodderomyces and Spathaspora through sequence comparison and ascospore morphology. The ex-type strain of H. nanyangensis is CBS 13020T ( = CICC 33021 = NYNU 13717. Furthermore, based on phenotypic and genotypic characteristics, C. insectamans is transferred to the newly described genus as Hemisphaericaspora insectamans comb. nov., in accordance with the changes in the International Code of Nomenclature for algae, fungi and plants.

  6. Metagenomic analysis reveals microbial diversity and function in the rhizosphere soil of a constructed wetland.

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    Bai, Yaohui; Liang, Jinsong; Liu, Ruiping; Hu, Chengzhi; Qu, Jiuhui

    2014-01-01

    Microbial communities play a critical role in the degradation of effluent contaminants in constructed wetlands. Many questions remain, however, regarding the role ofmicrobial communities in rhizospheric soil. In this study, we used metagenomic analysis to assess microbial community composition and function in a constructed wetland receiving surface water. The diversity of the microbial community of rhizosphere soil was found to be significantly greater than that of the wetland influent water. This enhancement is likely due to the availability of diverse habitats and nutrients provided by the wetland plants. From function annotation of metagenomic data, a number of biodegradation pathways associated with 14 xenobiotic compounds were identified in soil. Nitrogen fixation, nitrification and denitrification genes were semi-quantitatively analysed. By screening of manganese transformation genes, we found that the biological oxidation of Mn2+ (mainly catalysed by multicopper oxidase) in the influent water yielded insoluble Mn4+, which subsequently precipitated and were incorporated into the wetland soil. These data show that the use of metagenomic analysis can provide important new insights for the study of wetland ecosystems and, in particular, how biologically mediated transformation or degradation can be used to reduce contamination of point and non-point source wastewater. PMID:25145207

  7. Comparative proteomic analysis reveals mite (Varroa destructor) resistance-related proteins in Eastern honeybees (Apis cerana).

    Science.gov (United States)

    Ji, T; Shen, F; Liu, Z; Yin, L; Shen, J; Liang, Q; Luo, Y X

    2015-01-01

    The mite (Varroa destructor) has become the greatest threat to apiculture worldwide. As the original host of the mite, Apis cerana can effectively resist the mite. An increased understanding of the resistance mechanisms of Eastern honeybees against V. destructor may help researchers to protect other species against these parasites. In this study, the proteomes of 4 Apis cerana colonies were analyzed using an isobaric tag for relative and absolute quantitation technology. We determined the differences in gene and protein expression between susceptible and resistant colonies that were either unchallenged or challenged by V. destructor. The results showed that a total of 1532 proteins were identified. Gene Ontology enrichment analysis suggested that the transcription factors and basic metabolic and respiratory processes were efficient and feasible factors controlling this resistance, and 12 differentially expressed proteins were identified in Venn analysis. The results were validated by quantitative polymerase chain reaction. This study may provide insight into the genetic mechanisms underlying the resistance of honeybee to mites. PMID:26345948

  8. Microarray analysis reveals the actual specificity of enrichment media used for food safety assessment.

    Science.gov (United States)

    Kostić, Tanja; Stessl, Beatrix; Wagner, Martin; Sessitsch, Angela

    2011-06-01

    Microbial diagnostic microarrays are tools for simultaneous detection and identification of microorganisms in food, clinical, and environmental samples. In comparison to classic methods, microarray-based systems have the potential for high throughput, parallelism, and miniaturization. High specificity and high sensitivity of detection have been demonstrated. A microbial diagnostic microarray for the detection of the most relevant bacterial food- and waterborne pathogens and indicator organisms was developed and thoroughly validated. The microarray platform based on sequence-specific end labeling of oligonucleotides and the phylogenetically robust gyrB marker gene allowed a highly specific (resolution on genus and/or species level) and sensitive (0.1% relative and 10(4) CFU absolute sensitivity) detection of the target pathogens. In initial challenge studies of the applicability of microarray-based food analysis, we obtained results demonstrating the questionable specificity of standardized culture-dependent microbiological detection methods. Taking into consideration the importance of reliable food safety assessment methods, comprehensive performance assessment is essential. Results demonstrate the potential of this new pathogen diagnostic microarray to evaluate culture-based standard methods in microbiological food analysis.

  9. Proteomic analysis of pure human airway gland mucus reveals a large component of protective proteins.

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    Nam Soo Joo

    Full Text Available Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS. Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269-319 proteins per subject. We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38% had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican. A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment.

  10. Genome signature analysis of thermal virus metagenomes reveals Archaea and thermophilic signatures

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    Pride David T

    2008-09-01

    Full Text Available Abstract Background Metagenomic analysis provides a rich source of biological information for otherwise intractable viral communities. However, study of viral metagenomes has been hampered by its nearly complete reliance on BLAST algorithms for identification of DNA sequences. We sought to develop algorithms for examination of viral metagenomes to identify the origin of sequences independent of BLAST algorithms. We chose viral metagenomes obtained from two hot springs, Bear Paw and Octopus, in Yellowstone National Park, as they represent simple microbial populations where comparatively large contigs were obtained. Thermal spring metagenomes have high proportions of sequences without significant Genbank homology, which has hampered identification of viruses and their linkage with hosts. To analyze each metagenome, we developed a method to classify DNA fragments using genome signature-based phylogenetic classification (GSPC, where metagenomic fragments are compared to a database of oligonucleotide signatures for all previously sequenced Bacteria, Archaea, and viruses. Results From both Bear Paw and Octopus hot springs, each assembled contig had more similarity to other metagenome contigs than to any sequenced microbial genome based on GSPC analysis, suggesting a genome signature common to each of these extreme environments. While viral metagenomes from Bear Paw and Octopus share some similarity, the genome signatures from each locale are largely unique. GSPC using a microbial database predicts most of the Octopus metagenome has archaeal signatures, while bacterial signatures predominate in Bear Paw; a finding consistent with those of Genbank BLAST. When using a viral database, the majority of the Octopus metagenome is predicted to belong to archaeal virus Families Globuloviridae and Fuselloviridae, while none of the Bear Paw metagenome is predicted to belong to archaeal viruses. As expected, when microbial and viral databases are combined, each of

  11. Comparative transcriptomic analysis of roots of contrasting Gossypium herbaceum genotypes revealing adaptation to drought

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    Ranjan Alok

    2012-11-01

    Full Text Available Abstract Background Root length and its architecture govern the adaptability of plants to various stress conditions, including drought stress. Genetic variations in root growth, length, and architecture are genotypes dependent. In this study, we compared the drought-induced transcriptome of four genotypes of Gossypium herbaceum that differed in their drought tolerance adaptability. Three different methodologies, namely, microarray, pyrosequencing, and qRT–PCR, were used for transcriptome analysis and validation. Results The variations in root length and growth were found among four genotypes of G.herbaceum when exposed to mannitol-induced osmotic stress. Under osmotic stress, the drought tolerant genotypes Vagad and GujCot-21 showed a longer root length than did by drought sensitive RAHS-14 and RAHS-IPS-187. Further, the gene expression patterns in the root tissue of all genotypes were analyzed. We obtained a total of 794 differentially expressed genes by microarray and 104928 high-quality reads representing 53195 unigenes from the root transcriptome. The Vagad and GujCot-21 respond to water stress by inducing various genes and pathways such as response to stresses, response to water deprivation, and flavonoid pathways. Some key regulatory genes involved in abiotic stress such as AP2 EREBP, MYB, WRKY, ERF, ERD9, and LEA were highly expressed in Vagad and GujCot-21. The genes RHD3, NAP1, LBD, and transcription factor WRKY75, known for root development under various stress conditions, were expressed specifically in Vagad and GujCot-21. The genes related to peroxidases, transporters, cell wall-modifying enzymes, and compatible solutes (amino acids, amino sugars, betaine, sugars, or sugar alcohols were also highly expressed in Vagad and Gujcot-21. Conclusion Our analysis highlights changes in the expression pattern of genes and depicts a small but highly specific set of drought responsive genes induced in response to drought stress. Some of these

  12. Comparative genomic analysis reveals evidence of two novel Vibrio species closely related to V. cholerae

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    Brettin Thomas S

    2010-05-01

    Full Text Available Abstract Background In recent years genome sequencing has been used to characterize new bacterial species, a method of analysis available as a result of improved methodology and reduced cost. Included in a constantly expanding list of Vibrio species are several that have been reclassified as novel members of the Vibrionaceae. The description of two putative new Vibrio species, Vibrio sp. RC341 and Vibrio sp. RC586 for which we propose the names V. metecus and V. parilis, respectively, previously characterized as non-toxigenic environmental variants of V. cholerae is presented in this study. Results Based on results of whole-genome average nucleotide identity (ANI, average amino acid identity (AAI, rpoB similarity, MLSA, and phylogenetic analysis, the new species are concluded to be phylogenetically closely related to V. cholerae and V. mimicus. Vibrio sp. RC341 and Vibrio sp. RC586 demonstrate features characteristic of V. cholerae and V. mimicus, respectively, on differential and selective media, but their genomes show a 12 to 15% divergence (88 to 85% ANI and 92 to 91% AAI compared to the sequences of V. cholerae and V. mimicus genomes (ANI Vibrio sp. RC341 and Vibrio sp. RC586 share 2104 ORFs (59% and 2058 ORFs (56% with the published core genome of V. cholerae and 2956 (82% and 3048 ORFs (84% with V. mimicus MB-451, respectively. The novel species share 2926 ORFs with each other (81% Vibrio sp. RC341 and 81% Vibrio sp. RC586. Virulence-associated factors and genomic islands of V. cholerae and V. mimicus, including VSP-I and II, were found in these environmental Vibrio spp. Conclusions Results of this analysis demonstrate these two environmental vibrios, previously characterized as variant V. cholerae strains, are new species which have evolved from ancestral lineages of the V. cholerae and V. mimicus clade. The presence of conserved integration loci for genomic islands as well as evidence of horizontal gene transfer between these two new

  13. Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

    Directory of Open Access Journals (Sweden)

    Charles W Higdon

    Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

  14. Transcriptome Analysis Revealed the Embryo-Induced Gene Expression Patterns in the Endometrium from Meishan and Yorkshire Pigs

    Directory of Open Access Journals (Sweden)

    Jiangnan Huang

    2015-09-01

    Full Text Available The expression patterns in Meishan- and Yorkshire-derived endometrium during early (gestational day 15 and mid-gestation (gestational days 26 and 50 were investigated, respectively. Totally, 689 and 1649 annotated genes were identified to be differentially expressed in Meishan and Yorkshire endometrium during the three gestational stages, respectively. Hierarchical clustering analysis identified that, of the annotated differentially expressed genes (DEGs, 73 DEGs were unique to Meishan endometrium, 536 DEGs were unique to Yorkshire endometrium, and 228 DEGs were common in Meishan and Yorkshire endometriums. Subsequently, DEGs in each of the three types of expression patterns were grouped into four distinct categories according to the similarities in their temporal expression patterns. The expression patterns identified from the microarray analysis were validated by quantitative RT-PCR. The functional enrichment analysis revealed that the common DEGs were enriched in pathways of steroid metabolic process and regulation of retinoic acid receptor signaling. These unique DEGs in Meishan endometrium were involved in cell cycle and adherens junction. The DEGs unique to Yorkshire endometrium were associated with regulation of Rho protein signal transduction, maternal placenta development and cell proliferation. This study revealed the different gene expression patterns or pathways related to the endometrium remodeling in Meishan and Yorkshire pigs, respectively. These unique DEGs in either Meishan or Yorkshire endometriums may contribute to the divergence of the endometrium environment in the two pig breeds.

  15. Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by ‘Entotheonella’

    Science.gov (United States)

    Nakashima, Yu; Egami, Yoko; Kimura, Miki; Wakimoto, Toshiyuki; Abe, Ikuro

    2016-01-01

    Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas). Bioinformatic analysis of the gene product suggested its involvement in the biosynthesis of kasumigamide, a tetrapeptide originally isolated from freshwater free-living cyanobacterium Microcystis aeruginosa NIES-87. Subsequent investigation of the sponge metabolic profile revealed the presence of kasumigamide in the sponge extract. The kasumigamide producing bacterium was identified as an ‘Entotheonella’ sp. Moreover, an in silico analysis of kas gene homologs uncovered the presence of kas family genes in two additional bacteria from different phyla. The production of kasumigamide by distantly related multiple bacterial strains implicates horizontal gene transfer and raises the potential for a wider distribution across other bacterial groups. PMID:27732651

  16. Potential analysis reveals changing number of climate states during the last 60 kyr

    Directory of Open Access Journals (Sweden)

    V. N. Livina

    2009-09-01

    Full Text Available We develop and apply a new statistical method of potential analysis for detecting the number of states of a geophysical system, from its recorded time series. Estimation of the degree of a polynomial potential allows us to derive the number of potential wells in a system. The method correctly detects changes in the number of wells in artificial data. In ice-core proxy records of Greenland paleotemperature, a reduction in the number of climate states from two to one is detected sometime prior to the last glacial maximum (LGM, 23–19 kyr BP. This bifurcation can be interpreted as loss of stability of the warm interstadial state of the Dansgaard-Oeschger events. In data spanning the last glacial termination, up to four climate states are detected, plausibly representing the LGM, Bolling-Allerod, Younger Dryas, and the Holocene. The proposed method can be applied to a wide range of geophysical time series exhibiting bifurcations.

  17. Spectral Analysis by XANES Reveals that GPNMB Influences the Chemical Composition of Intact Melanosomes

    Energy Technology Data Exchange (ETDEWEB)

    T Haraszti; C Trantow; A Hedberg-Buenz; M Grunze; M Anderson

    2011-12-31

    GPNMB is a unique melanosomal protein. Unlike many melanosomal proteins, GPNMB has not been associated with any forms of albinism, and it is unclear whether GPNMB has any direct influence on melanosomes. Here, melanosomes from congenic strains of C57BL/6J mice mutant for Gpnmb are compared to strain-matched controls using standard transmission electron microscopy and synchrotron-based X-ray absorption near-edge structure analysis (XANES). Whereas electron microscopy did not detect any ultrastructural changes in melanosomes lacking functional GPNMB, XANES uncovered multiple spectral phenotypes. These results directly demonstrate that GPNMB influences the chemical composition of melanosomes and more broadly illustrate the potential for using genetic approaches in combination with nano-imaging technologies to study organelle biology.

  18. Analysis of protein phosphorylation in nerve terminal reveals extensive changes in active zone proteins upon exocytosis.

    Science.gov (United States)

    Kohansal-Nodehi, Mahdokht; Chua, John Je; Urlaub, Henning; Jahn, Reinhard; Czernik, Dominika

    2016-01-01

    Neurotransmitter release is mediated by the fast, calcium-triggered fusion of synaptic vesicles with the presynaptic plasma membrane, followed by endocytosis and recycling of the membrane of synaptic vesicles. While many of the proteins governing these processes are known, their regulation is only beginning to be understood. Here we have applied quantitative phosphoproteomics to identify changes in phosphorylation status of presynaptic proteins in resting and stimulated nerve terminals isolated from the brains of Wistar rats. Using rigorous quantification, we identified 252 phosphosites that are either up- or downregulated upon triggering calcium-dependent exocytosis. Particularly pronounced were regulated changes of phosphosites within protein constituents of the presynaptic active zone, including bassoon, piccolo, and RIM1. Additionally, we have mapped kinases and phosphatases that are activated upon stimulation. Overall, our study provides a snapshot of phosphorylation changes associated with presynaptic activity and provides a foundation for further functional analysis of key phosphosites involved in presynaptic plasticity. PMID:27115346

  19. Biosynthetic Pathway for the Epipolythiodioxopiperazine Acetylaranotin in Aspergillus terreus Revealed by Genome-based Deletion Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Chun-Jun; Yeh, Hsu-Hua; Chiang, Yi Ming; Sanchez, James F.; Chang, ShuLin; Bruno, Kenneth S.; Wang, Clay C.

    2013-04-15

    Abstract Epipolythiodioxopiperazines (ETPs) are a class of fungal secondary metabolites derived from cyclic peptides. Acetylaranotin belongs to one structural subgroup of ETPs characterized by the presence of a seven-membered dihydrooxepine ring. Defining the genes involved in acetylaranotin biosynthesis should provide a means to increase production of these compounds and facilitate the engineering of second-generation molecules. The filamentous fungus Aspergillus terreus produces acetylaranotin and related natural products. Using targeted gene deletions, we have identified a cluster of 9 genes including one nonribosomal peptide synthase gene, ataP, that is required for acetylaranotin biosynthesis. Chemical analysis of the wild type and mutant strains enabled us to isolate seventeen natural products that are either intermediates in the normal biosynthetic pathway or shunt products that are produced when the pathway is interrupted through mutation. Nine of the compounds identified in this study are novel natural products. Our data allow us to propose a complete biosynthetic pathway for acetylaranotin and related natural products.

  20. Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells

    DEFF Research Database (Denmark)

    Lauber, Chris; Vieyres, Gabrielle; Terczynska-Dyla, Ewa;

    2015-01-01

    4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using...... transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified...... genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium....

  1. NMR Based Cerebrum Metabonomic Analysis Reveals Simultaneous Interconnected Changes during Chick Embryo Incubation.

    Directory of Open Access Journals (Sweden)

    Yue Feng

    Full Text Available To find out if content changes of the major functional cerebrum metabolites are interconnected and formed a network during the brain development, we obtained high-resolution magic-angle-spinning (HR-MAS 1H NMR spectra of cerebrum tissues of chick embryo aged from incubation day 10 to 20, and postnatal day 1, and analyzed the data with principal component analysis (PCA. Within the examined time window, 26 biological important molecules were identified and 12 of them changed their relative concentration significantly in a time-dependent manner. These metabolites are generally belonged to three categories, neurotransmitters, nutrition sources, and neuronal or glial markers. The relative concentration changes of the metabolites were interconnected among/between the categories, and, more interestingly, associated with the number and size of Nissl-positive neurons. These results provided valuable biochemical and neurochemical information to understand the development of the embryonic brain.

  2. Global meta-analysis reveals low consistency of biodiversity congruence relationships.

    Science.gov (United States)

    Westgate, Martin J; Barton, Philip S; Lane, Peter W; Lindenmayer, David B

    2014-01-01

    Knowledge of the number and distribution of species is fundamental to biodiversity conservation efforts, but this information is lacking for the majority of species on earth. Consequently, subsets of taxa are often used as proxies for biodiversity; but this assumes that different taxa display congruent distribution patterns. Here we use a global meta-analysis to show that studies of cross-taxon congruence rarely give consistent results. Instead, species richness congruence is highest at extreme spatial scales and close to the equator, while congruence in species composition is highest at large extents and grain sizes. Studies display highest variance in cross-taxon congruence when conducted in areas with dissimilar areal extents (for species richness) or latitudes (for species composition). These results undermine the assumption that a subset of taxa can be representative of biodiversity. Therefore, researchers whose goal is to prioritize locations or actions for conservation should use data from a range of taxa. PMID:24844928

  3. Photoactivation mechanisms of flavin-binding photoreceptors revealed through ultrafast spectroscopy and global analysis methods.

    Science.gov (United States)

    Mathes, Tilo; van Stokkum, Ivo H M; Kennis, John T M

    2014-01-01

    Flavin-binding photoreceptor proteins use the isoalloxazine moiety of flavin cofactors to absorb light in the blue/UV-A wavelength region and subsequently translate it into biological information. The underlying photochemical reactions and protein structural dynamics are delicately tuned by the protein environment and represent fundamental reactions in biology and chemistry. Due to their photo-switchable nature, these proteins can be studied efficiently with laser-flash induced transient absorption and emission spectroscopy with temporal precision down to the femtosecond time domain. Here, we describe the application of both visible and mid-IR ultrafast transient absorption and time-resolved fluorescence methods in combination with sophisticated global analysis procedures to elucidate the photochemistry and signal transduction of BLUF (Blue light receptors using FAD) and LOV (Light oxygen voltage) photoreceptor domains.

  4. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Lancet Jeffrey E

    2004-08-01

    Full Text Available Abstract Background Farnesyl protein transferase inhibitors (FTIs were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777 has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML. Methods Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. Results The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. Conclusions The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity.

  5. [Phylogenetic relationships and intraspecific variation of D-genome Aegilops L. as revealed by RAPD analysis].

    Science.gov (United States)

    Goriunova, S V; Kochieva, E Z; Chikida, N N; Pukhal'skiĭ, V A

    2004-05-01

    RAPD analysis was carried out to study the genetic variation and phylogenetic relationships of polyploid Aegilops species, which contain the D genome as a component of the alloploid genome, and diploid Aegilops tauschii, which is a putative donor of the D genome for common wheat. In total, 74 accessions of six D-genome Aegilops species were examined. The highest intraspecific variation (0.03-0.21) was observed for Ae. tauschii. Intraspecific distances between accessions ranged 0.007-0.067 in Ae. cylindrica, 0.017-0.047 in Ae. vavilovii, and 0.00-0.053 in Ae. juvenalis. Likewise, Ae. ventricosa and Ae. crassa showed low intraspecific polymorphism. The among-accession difference in alloploid Ae. ventricosa (genome DvNv) was similar to that of one parental species, Ae. uniaristata (N), and substantially lower than in the other parent, Ae. tauschii (D). The among-accession difference in Ae. cylindrica (CcDc) was considerably lower than in either parent, Ae. tauschii (D) or Ae. caudata (C). With the exception of Ae. cylindrica, all D-genome species--Ae. tauschii (D), Ae. ventricosa (DvNv), Ae. crassa (XcrDcrl and XcrDcrlDcr2), Ae. juvenalis (XjDjUj), and Ae. vavilovii (XvaDvaSva)--formed a single polymorphic cluster, which was distinct from clusters of other species. The only exception, Ae. cylindrica, did not group with the other D-genome species, but clustered with Ae. caudata (C), a donor of the C genome. The cluster of these two species was clearly distinct from the cluster of the other D-genome species and close to a cluster of Ae. umbellulata (genome U) and Ae. ovata (genome UgMg). Thus, RAPD analysis for the first time was used to estimate and to compare the interpopulation polymorphism and to establish the phylogenetic relationships of all diploid and alloploid D-genome Aegilops species.

  6. Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1

    Science.gov (United States)

    Ye, Zhenqing; Chen, Zhong; Sunkel, Benjamin; Frietze, Seth; Huang, Tim H.-M.; Wang, Qianben; Jin, Victor X.

    2016-01-01

    The compaction of nucleosomal structures creates a barrier for DNA-binding transcription factors (TFs) to access their cognate cis-regulatory elements. Pioneer factors (PFs) such as FOXA1 are able to directly access these cis-targets within compact chromatin. However, how these PFs interplay with nucleosomes remains to be elucidated, and is critical for us to understand the underlying mechanism of gene regulation. Here, we have conducted a computational analysis on a strand-specific paired-end ChIP-exo (termed as ChIP-ePENS) data of FOXA1 in LNCaP cells by our novel algorithm ePEST. We find that FOXA1 chromatin binding occurs via four distinct border modes (or footprint boundary patterns), with a preferential footprint boundary patterns relative to FOXA1 motif orientation. In addition, from this analysis three fundamental nucleotide positions (oG, oS and oH) emerged as major determinants for blocking exo-digestion and forming these four distinct border modes. By integrating histone MNase-seq data, we found an astonishingly consistent, ‘well-positioned’ configuration occurs between FOXA1 motifs and dyads of nucleosomes genome-wide. We further performed ChIP-seq of eight chromatin remodelers and found an increased occupancy of these remodelers on FOXA1 motifs for all four border modes (or footprint boundary patterns), indicating the full occupancy of FOXA1 complex on the three blocking sites (oG, oS and oH) likely produces an active regulatory status with well-positioned phasing for protein binding events. Together, our results suggest a positional-nucleosome-oriented accessing model for PFs seeking target motifs, in which FOXA1 can examine each underlying DNA nucleotide and is able to sense all potential motifs regardless of whether they face inward or outward from histone octamers along the DNA helix axis. PMID:27458208

  7. Gene Regulatory Network Analysis Reveals Differences in Site-specific Cell Fate Determination in Mammalian Brain

    Directory of Open Access Journals (Sweden)

    Gokhan eErtaylan

    2014-12-01

    Full Text Available Neurogenesis - the generation of new neurons - is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ lining the walls of the lateral ventricles; and the subgranular zone (SGZ of the dentate gyrus of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a and Nr3c1.We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report thirty-one candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar - Pax6 in SVZ and Sox2 - Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact.Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis.

  8. Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Lei Jin; Yan Zhang; Hui Li; Ling Yao; Da Fu; Xuebiao Yao; Lisa X Xu; Xiaofang Hu; Guohong Hu

    2012-01-01

    Bone metastasis is a frequent complication of breast cancer and a common cause of morbidity and mortality from the disease.During metastasis secreted proteins play crucial roles in the interactions between cancer cells and host stroma.To characterize the secreted proteins that are associated with breast cancer bone metastasis,we preformed a label-free proteomic analysis to compare the secretomes of four MDA-MB-231 (MDA231) derivative cell lines with varied capacities of bone metastasis.A total of 128 proteins were found to be consistently up-/down-regulated in the conditioned medium of bone-tropic cancer cells.The enriched molecular functions of the altered proteins included receptor binding and peptidase inhibition.Through additional transcriptomic analyses of breast cancer cells,we selected cystatin E/M (CST6),a cysteine protease inhibitor down-regulated in bone-metastatic cells,for further functional studies.Our results showed that CST6 suppressed the proliferation,colony formation,migration and invasion of breast cancer cells.The suppressive function against cancer cell motility was carried out by cancer cell-derived soluble CST6.More importantly,ectopic expression of CST6 in cancer cells rescued mice from overt osteolytic metastasis and deaths in the animal study,while CST6 knockdown markedly enhanced cancer cell bone metastasis and shortened animal survival.Overall,our study provided a systemic secretome analysis of breast cancer bone tropism and established secreted CST6 as a bonafide suppressor of breast cancer osteolytic metastasis.

  9. Transcriptome Analysis of Pepper (Capsicum annuum Revealed a Role of 24-epibrassinolide in Response to Chilling

    Directory of Open Access Journals (Sweden)

    Li Jie

    2016-08-01

    Full Text Available Brassinosteroids (BRs have positive effects on many processes during plant growth, development, and various abiotic stress responses. However, little information is available regarding the global gene expression of BRs in response to chilling stress in pepper. In this study, we used RNA sequencing to determine the molecular roles of 24-epibrassinolide (EBR during a chilling stress response. There were 39,829 transcripts, and, among them, 656 were differently-expressed genes (DEGs following EBR treatment (Chill+EBR compared with the control (Chill only, including 335 up-regulated and 321 down-regulated DEGs. We selected 20 genes out of the 656 DEGs for RT-qPCR analysis to confirm the RNA-Seq. Based on GO enrich and KEGG pathway analysis, we found that photosynthesis was significantly up-enriched in biological processes, accompanied by significant increases in the net photosynthetic rate (Pn, Fv/Fm and chlorophyll content. Furthermore, the results indicate that EBR enhanced endogenous levels of salicylic acid (SA and jasmonic acid (JA while suppressing the ethylene (ETH biosynthesis pathway, suggesting that BRs function via a synergistic cross-talk with SA, JA and ETH signaling pathways in response to chilling stress. In addition, EBR induced cellulose synthase-like protein and UDP-glycosyltransferase, suggesting a contribution to the formation of cell wall and hormone metabolism. EBR also triggered the calcium signaling transduction in cytoplasm, and activated the expression of cellular redox homeostasis related genes, such as GSTX1, PER72, and CAT2. This work, therefor, identified the specific genes showed different expression patterns in EBR-treated pepper and associated with the processes of hormone metabolism, redox, signaling, transcription and defense. Our study provides the first evidence of the potent roles of BRs, at the transcription level, to induce the tolerance to chilling stress in pepper as a function of the combination of the

  10. Principal component analysis reveals gender-specific predictors of cardiometabolic risk in 6th graders

    Directory of Open Access Journals (Sweden)

    Peterson Mark D

    2012-11-01

    Full Text Available Abstract Background The purpose of this study was to determine the sex-specific pattern of pediatric cardiometabolic risk with principal component analysis, using several biological, behavioral and parental variables in a large cohort (n = 2866 of 6th grade students. Methods Cardiometabolic risk components included waist circumference, fasting glucose, blood pressure, plasma triglycerides levels and HDL-cholesterol. Principal components analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore. Stratified risk components and MetScore were analyzed for association with age, body mass index (BMI, cardiorespiratory fitness (CRF, physical activity (PA, and parental factors. Results In both boys and girls, BMI and CRF were associated with multiple risk components, and overall MetScore. Maternal smoking was associated with multiple risk components in girls and boys, as well as MetScore in boys, even after controlling for children’s BMI. Paternal family history of early cardiovascular disease (CVD and parental age were associated with increased blood pressure and MetScore for girls. Children’s PA levels, maternal history of early CVD, and paternal BMI were also indicative for various risk components, but not MetScore. Conclusions Several biological and behavioral factors were independently associated with children’s cardiometabolic disease risk, and thus represent a unique gender-specific risk profile. These data serve to bolster the independent contribution of CRF, PA, and family-oriented healthy lifestyles for improving children’s health.

  11. An overview on preseismic anomalies in LF radio signals revealed in Italy by wavelet analysis

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    A. Ermini

    2008-06-01

    Full Text Available Since 1996, the electric field strength of the two broadcasting stations MCO (f=216 kHz, southeast France and CZE (f=270 kHz, Czech Republic has been sampled every ten minutes by a receiver (AS located in central Italy. Here, we review the results obtained by a detailed analysis applied to the data recorded from February 1996 up to December 2004. At first, the daytime and nighttime data were extracted and then, in the daytime data, the data collected in winter were separated from those collected in summer. On the second step the wavelet transform was applied. The results of this analysis are radio anomalies detected as earthquake precursors both for MCO and CZE data. In particular, regarding the MCO data, the main result was the appearance of a very clear anomaly during May-August 1998, at daytime and at nighttime. Such an anomaly can be considered as a precursor of a seismic sequence started on August 15, 1998 with 17 earthquakes (M=2.2-4.6 on the Reatini mountains, a seismogenic zone located 30 km far from the AS receiver along the path MCO-AS. As concerns with the CZE data, the first result was obtained from the summer daytime data and it was the appearance of a very clear anomaly during August-September 1997, that can be considered a precursor of the two earthquakes with magnitude M=5.6 and M=5.9 that occurred on September 26 in the Umbria-Marche region (Central Italy. The second result was the appearance of an anomaly during February-March 1998, at daytime and at nighttime, that can be related to the preparatory phase of the strong (M=5.1-6.0 Slovenia seismic sequence that occurred in a zone lying in the middle of the CZE-AS path.

  12. Transfer Analysis of Provenance Trials Reveals Macroclimatic Adaptedness of European Beech (Fagus sylvatica L.

    Directory of Open Access Journals (Sweden)

    RASZTOVITS, Ervin

    2009-01-01

    Full Text Available The aim of the study was to analyse provenance tests of beech situated close to theSoutheastern-continental limits of the species, in order to develop a response model of adaptation andplasticity of populations on evolutionary-ecological basis, following sudden climatic changes as aresult of transplanting. Modelling of juvenile height was performed with the help of ecodistancevariables. The concept of transfer analysis and ecodistance is based on the hypothesis that phenotypicresponse to macroclimatic changes depends on the inherited adaptive potential of the population andon the magnitude and direction of experienced environmental change. In common garden experiments,the transfer to the planting site is interpreted as simulation of environmental change. The applicationof ecodistance of transfer for evaluating common garden experiments provides much neededquantitative information about response of tree populations to predicted climatic changes.The analysis of three field experiments of European beech in SE Europe invalidate earlier doubtsabout the existence of macroclimatic adaptation patterns in juvenile growth and justify restrictions ofuse of reproductive material on the basis of evolutionary ecology. The presented model illustrates thatresponse to climatic change is regionally divergent, depending on testing conditions and on hereditarytraits. In particular, climatic warming in the central-northern part of the range may lead to productionincrease. However, under the stressful and uncertain conditions at the lower (xeric limit of thespecies, growth depression and vitality loss are predicted. The deviating behaviour of higher elevationprovenances support their separate treatment.The results may be utilised in climate change adaptation and mitigation policy in forestry andnature conservation, to revise rules for use of reproductive material and also for validatingevolutionary and ecological hypotheses related to climate change effects.

  13. Muscle modifications in fibromyalgic patients revealed by surface electromyography (SEMG analysis

    Directory of Open Access Journals (Sweden)

    Zirafa Cristina

    2009-04-01

    Full Text Available Abstract Background Several studies have been carried out in order to investigate surface electromyography (SEMG response on fibromyalgic (FM patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease. Methods SEMG was recorded in 100 FM women (48.10 ± 11.96 yr and in 50 healthy women (48.60 ± 11.18 yr, from the tibialis anterior and the distal part of vastus medialis muscle during isometric contraction. Initial values and rate of change of median spectral frequency (MDF and conduction velocity (CV of the SEMG signal were calculated. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, tiredness were evaluated and the relationships between these data and the SEMG results were also studied. For the statistical analysis Mann-Whitney test, chi-square test and Spearman correlation were used. Results MDF absolute values and the so-called Fatigue Index (FI were significantly lower (p Conclusion We have found some interesting muscle modifications in FM patients with respect to healthy controls, regarding MDF, CV and FI values which resulted significantly lower in FM. Patients might have a different fiber recruitment or a possible atrophy of type II fibers suggesting that they are not able to reach muscle relaxation.

  14. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.

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    Jesse F Gregory

    Full Text Available Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5'-phosphate (PLP serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23 were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD to 21.5±4.6 nmol/L (P<0.0001 and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001. Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by (1H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS. Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001 and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05. Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05, but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.

  15. Eurytemora carolleeae in the Laurentian Great Lakes revealed by phylogenetic and morphological analysis

    Science.gov (United States)

    Vasquez, Adrian A.; Hudson, Patrick L.; Fujimoto, Masanori; Keeler, Kevin M.; Armenio, Patricia M.; Ram, Jeffrey L.

    2016-01-01

    In the Laurentian Great Lakes, specimens of Eurytemora have been reported asEurytemora affinis since its invasion in the late 1950s. During an intensive collection of aquatic invertebrates for morphological and molecular identification in Western Lake Erie in 2012-2013, several specimens of Eurytemora were collected. Analysis of these specimens identified them as the recently described species Eurytemora carolleeaeAlekseev and Souissi 2011. This result led us to assess E. carolleeae’s identifying features, geographic distribution and historical presence in the Laurentian Great Lakes in view of its recent description in 2011. Cytochrome oxidase I (COI) DNA sequences ofEurytemora specimens were identified as closer (2 - 4% different) to recently describedE. carolleeae than to most E. affinis sequences (14% different). Eurytemora from other areas of the Great Lakes and from North American rivers as far west as South Dakota (Missouri River) and east to Delaware (Christina River) also keyed to E. carolleeae. Morphological analysis of archival specimens from 1962 and from all the Great Lakes was identified as E. carolleeae. Additionally, Eurytemora drawings in previous publications were reassessed to determine if the species was E. carolleeae and are reported here. Additional morphological characters that may distinguish North AmericanE. carolleeae from other taxa are also described. We conclude that E. carolleeae is the correct name for the species of Eurytemora that has inhabited the Great Lakes since its invasion, as established by both morphological and COI sequence comparisons to reference keys and sequence databases in present and archival specimens.

  16. Transcriptome Analysis of Pepper (Capsicum annuum) Revealed a Role of 24-Epibrassinolide in Response to Chilling

    Science.gov (United States)

    Li, Jie; Yang, Ping; Kang, Jungen; Gan, Yantai; Yu, Jihua; Calderón-Urrea, Alejandro; Lyu, Jian; Zhang, Guobin; Feng, Zhi; Xie, Jianming

    2016-01-01

    Brassinosteroids (BRs) have positive effects on many processes during plant growth, development, and various abiotic stress responses. However, little information is available regarding the global gene expression of BRs in response to chilling stress in pepper. In this study, we used RNA sequencing to determine the molecular roles of 24-epibrassinolide (EBR) during a chilling stress response. There were 39,829 transcripts, and, among them, 656 were differently-expressed genes (DEGs) following EBR treatment (Chill+EBR) compared with the control (Chill only), including 335 up-regulated and 321 down-regulated DEGs. We selected 20 genes out of the 656 DEGs for RT-qPCR analysis to confirm the RNA-Seq. Based on GO enrich and KEGG pathway analysis, we found that photosynthesis was significantly up-enriched in biological processes, accompanied by significant increases in the net photosynthetic rate (Pn), Fv/Fm, and chlorophyll content. Furthermore, the results indicate that EBR enhanced endogenous levels of salicylic acid (SA) and jasmonic acid (JA) while suppressing the ethylene (ETH) biosynthesis pathway, suggesting that BRs function via a synergistic cross-talk with SA, JA, and ETH signaling pathways in response to chilling stress. In addition, EBR induced cellulose synthase-like protein and UDP-glycosyltransferase, suggesting a contribution to the formation of cell wall and hormone metabolism. EBR also triggered the calcium signaling transduction in cytoplasm, and activated the expression of cellular redox homeostasis related genes, such as GSTX1, PER72, and CAT2. This work, therefor, identified the specific genes showed different expression patterns in EBR-treated pepper and associated with the processes of hormone metabolism, redox, signaling, transcription, and defense. Our study provides the first evidence of the potent roles of BRs, at the transcription level, to induce the tolerance to chilling stress in pepper as a function of the combination of the

  17. De novo Transcriptome Analysis of Sinapis alba in Revealing the Glucosinolate and Phytochelatin Pathways

    Science.gov (United States)

    Zhang, Xiaohui; Liu, Tongjin; Duan, Mengmeng; Song, Jiangping; Li, Xixiang

    2016-01-01

    Sinapis alba is an important condiment crop and can also be used as a phytoremediation plant. Though it has important economic and agronomic values, sequence data, and the genetic tools are still rare in this plant. In the present study, a de novo transcriptome based on the transcriptions of leaves, stems, and roots was assembled for S. alba for the first time. The transcriptome contains 47,972 unigenes with a mean length of 1185 nt and an N50 of 1672 nt. Among these unigenes, 46,535 (97%) unigenes were annotated by at least one of the following databases: NCBI non-redundant (Nr), Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology (GO), and Clusters of Orthologous Groups of proteins (COGs). The tissue expression pattern profiles revealed that 3489, 1361, and 8482 unigenes were predominantly expressed in the leaves, stems, and roots of S. alba, respectively. Genes predominantly expressed in the leaf were enriched in photosynthesis- and carbon fixation-related pathways. Genes predominantly expressed in the stem were enriched in not only pathways related to sugar, ether lipid, and amino acid metabolisms but also plant hormone signal transduction and circadian rhythm pathways, while the root-dominant genes were enriched in pathways related to lignin and cellulose syntheses, involved in plant-pathogen interactions, and potentially responsible for heavy metal chelating, and detoxification. Based on this transcriptome, 14,727 simple sequence repeats (SSRs) were identified, and 12,830 pairs of primers were developed for 2522 SSR-containing unigenes. Additionally, the glucosinolate (GSL) and phytochelatin metabolic pathways, which give the characteristic flavor and the heavy metal tolerance of this plant, were intensively analyzed. The genes of aliphatic GSLs pathway were predominantly expressed in roots. The absence of aliphatic GSLs in leaf tissues was due to the shutdown of BCAT4, MAM1, and CYP79F1 expressions. Glutathione was extensively

  18. Complexity of genome evolution by segmental rearrangement in Brassica rapa revealed by sequence-level analysis

    Directory of Open Access Journals (Sweden)

    Paterson Andrew H

    2009-11-01

    Full Text Available Abstract Background The Brassica species, related to Arabidopsis thaliana, include an important group of crops and represent an excellent system for studying the evolutionary consequences of polyploidy. Previous studies have led to a proposed structure for an ancestral karyotype and models for the evolution of the B. rapa genome by triplication and segmental rearrangement, but these have not been validated at the sequence level. Results We developed computational tools to analyse the public collection of B. rapa BAC end sequence, in order to identify candidates for representing collinearity discontinuities between the genomes of B. rapa and A. thaliana. For each putative discontinuity, one of the BACs was sequenced and analysed for collinearity with the genome of A. thaliana. Additional BAC clones were identified and sequenced as part of ongoing efforts to sequence four chromosomes of B. rapa. Strikingly few of the 19 inter-chromosomal rearrangements corresponded to the set of collinearity discontinuities anticipated on the basis of previous studies. Our analyses revealed numerous instances of newly detected collinearity blocks. For B. rapa linkage group A8, we were able to develop a model for the derivation of the chromosome from the ancestral karyotype. We were also able to identify a rearrangement event in the ancestor of B. rapa that was not shared with the ancestor of A. thaliana, and is represented in triplicate in the B. rapa genome. In addition to inter-chromosomal rearrangements, we identified and analysed 32 BACs containing the end points of segmental inversion events. Conclusion Our results show that previous studies of segmental collinearity between the A. thaliana, Brassica and ancestral karyotype genomes, although very useful, represent over-simplifications of their true relationships. The presence of numerous cryptic collinear genome segments and the frequent occurrence of segmental inversions mean that inference of the positions

  19. Comparative genomic analysis reveals 2-oxoacid dehydrogenase complex lipoylation correlation with aerobiosis in archaea.

    Directory of Open Access Journals (Sweden)

    Kirill Borziak

    the archaea, the extension of comparative genomic pathway profiling to broader metabolic and homeostasis networks should be useful in revealing characteristics from metagenomic datasets related to adaptations to diverse environments.

  20. De novo transcriptome analysis of Sinapis alba in revealing the glucosinolate and phytochelatin pathways

    Directory of Open Access Journals (Sweden)

    Xiaohui eZhang

    2016-03-01

    Full Text Available Sinapis alba is an important condiment crop and can also be used as a phytoremediation plant. Though it has important economic and agronomic values, sequence data and the genetic tools are still rare in this plant. In the present study, a de novo transcriptome based on the transcriptions of leaves, stems and roots was assembled for S. alba for the first time. The transcriptome contains 47,972 unigenes with a mean length of 1,185 nt and an N50 of 1,672 nt. Among these unigenes, 46,535 (97% unigenes were annotated by at least one of the following databases: NCBI non-redundant (Nr, Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG pathway, Gene Ontology (GO, and Clusters of Orthologous Groups of proteins (COGs. The tissue expression pattern profiles revealed that 3,489, 1,361 and 8,482 unigenes were predominantly expressed in the leaves, stems and roots of S. alba, respectively. Genes predominantly expressed in the leaf were enriched in photosynthesis- and carbon fixation-related pathways. Genes predominantly expressed in the stem were enriched in not only pathways related to sugar, ether lipid and amino acid metabolisms but also plant hormone signal transduction and circadian rhythm pathways, while the root-dominant genes were enriched in pathways related to lignin and cellulose syntheses, involved in plant-pathogen interactions, and potentially responsible for heavy metal chelating and detoxification. Based on this transcriptome, 14,727 simple sequence repeats (SSRs were identified, and 12,830 pairs of primers were developed for 2,522 SSR-containing unigenes. Additionally, the glucosinolate (GSL and phytochelatin metabolic pathways, which give the characteristic flavor and the heavy metal tolerance of this plant, were intensively analyzed. The genes of aliphatic GSLs pathway were predominantly expressed in roots. The absence of aliphatic GSLs in leaf tissues was due to the shutdown of BCAT4, MAM1 and CYP79F1 expressions. Glutathione was

  1. Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut.

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    Sudarshan Anand Shetty

    Full Text Available With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563 and BL7 (DSM25562, isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460 highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the "glycobiome" based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate, vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the

  2. Genome-based metabolic mapping and 13C flux analysis reveal systematic properties of an oleaginous microalga Chlorella protothecoides.

    Science.gov (United States)

    Wu, Chao; Xiong, Wei; Dai, Junbiao; Wu, Qingyu

    2015-02-01

    Integrated and genome-based flux balance analysis, metabolomics, and (13)C-label profiling of phototrophic and heterotrophic metabolism in Chlorella protothecoides, an oleaginous green alga for biofuel. The green alga Chlorella protothecoides, capable of autotrophic and heterotrophic growth with rapid lipid synthesis, is a promising candidate for biofuel production. Based on the newly available genome knowledge of the alga, we reconstructed the compartmentalized metabolic network consisting of 272 metabolic reactions, 270 enzymes, and 461 encoding genes and simulated the growth in different cultivation conditions with flux balance analysis. Phenotype-phase plane analysis shows conditions achieving theoretical maximum of the biomass and corresponding fatty acid-producing rate for phototrophic cells (the ratio of photon uptake rate to CO2 uptake rate equals 8.4) and heterotrophic ones (the glucose uptake rate to O2 consumption rate reaches 2.4), respectively. Isotope-assisted liquid chromatography-mass spectrometry/mass spectrometry reveals higher metabolite concentrations in the glycolytic pathway and the tricarboxylic acid cycle in heterotrophic cells compared with autotrophic cells. We also observed enhanced levels of ATP, nicotinamide adenine dinucleotide (phosphate), reduced, acetyl-Coenzyme A, and malonyl-Coenzyme A in heterotrophic cells consistently, consistent with a strong activity of lipid synthesis. To profile the flux map in experimental conditions, we applied nonstationary (13)C metabolic flux analysis as a complementing strategy to flux balance analysis. The result reveals negligible photorespiratory fluxes and a metabolically low active tricarboxylic acid cycle in phototrophic C. protothecoides. In comparison, high throughput of amphibolic reactions and the tricarboxylic acid cycle with no glyoxylate shunt activities were measured for heterotrophic cells. Taken together, the metabolic network modeling assisted by experimental metabolomics and (13)C

  3. Cloning and Analysis of a Large Plasmid pBMB165 from Bacillus thuringiensis Revealed a Novel Plasmid Organization

    OpenAIRE

    Yueying Wang; Donghai Peng; Zhaoxia Dong; Lei Zhu; Suxia Guo; Ming Sun

    2013-01-01

    In this study, we report a rapid cloning strategy for large native plasmids via a contig linkage map by BAC libraries. Using this method, we cloned a large plasmid pBMB165 from Bacillus thuringiensis serovar tenebrionis strain YBT-1765. Complete sequencing showed that pBMB165 is 77,627 bp long with a GC-content of 35.36%, and contains 103 open reading frames (ORFs). Sequence analysis and comparison reveals that pBMB165 represents a novel plasmid organization: it mainly consists of a pXO2-like...

  4. Morphometric differences in planum temporale in schizophrenia and bipolar disorder revealed by statistical analysis of labeled cortical depth maps

    OpenAIRE

    Ceyhan, Elvan; Ratnanather, J. Tilak; Cebron, Shannon; Postell, Elizabeth; Pisano, Dominic V.; Poynton, Clare B.; Crocker, Britni; Honeycutt, Nancy A.; Mahon, Pamela B.; Barta, Patrick E.

    2014-01-01

    PSYCHIATRY METHODS ARTICLE published: 01 August 2014 doi: 10.3389/fpsyt.2014.00094 Morphometric differences in planum temporale in schizophrenia and bipolar disorder revealed by statistical analysis of labeled cortical depth maps J. Tilak Ratnanather 1,2,3*, Shannon Cebron1, Elvan Ceyhan4, Elizabeth Postell 1, DominicV. Pisano1, Clare B. Poynton1, Britni Crocker 1, Nancy A. Honeycutt 5, Pamela B. Mahon5 and Patrick E. Barta1,2 1 Center for Imaging Science, Johns Hop...

  5. N-gram analysis of 970 microbial organisms reveals presence of biological language models

    Directory of Open Access Journals (Sweden)

    Ganapathiraju Madhavi K

    2011-01-01

    Full Text Available Abstract Background It has been suggested previously that genome and proteome sequences show characteristics typical of natural-language texts such as "signature-style" word usage indicative of authors or topics, and that the algorithms originally developed for natural language processing may therefore be applied to genome sequences to draw biologically relevant conclusions. Following this approach of 'biological language modeling', statistical n-gram analysis has been applied for comparative analysis of whole proteome sequences of 44 organisms. It has been shown that a few particular amino acid n-grams are found in abundance in one organism but occurring very rarely in other organisms, thereby serving as genome signatures. At that time proteomes of only 44 organisms were available, thereby limiting the generalization of this hypothesis. Today nearly 1,000 genome sequences and corresponding translated sequences are available, making it feasible to test the existence of biological language models over the evolutionary tree. Results We studied whole proteome sequences of 970 microbial organisms using n-gram frequencies and cross-perplexity employing the Biological Language Modeling Toolkit and Patternix Revelio toolkit. Genus-specific signatures were observed even in a simple unigram distribution. By taking statistical n-gram model of one organism as reference and computing cross-perplexity of all other microbial proteomes with it, cross-perplexity was found to be predictive of branch distance of the phylogenetic tree. For example, a 4-gram model from proteome of Shigellae flexneri 2a, which belongs to the Gammaproteobacteria class showed a self-perplexity of 15.34 while the cross-perplexity of other organisms was in the range of 15.59 to 29.5 and was proportional to their branching distance in the evolutionary tree from S. flexneri. The organisms of this genus, which happen to be pathotypes of E.coli, also have the closest perplexity values with

  6. Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development

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    Putta Srikrishna

    2010-06-01

    Full Text Available Abstract Background The Mexican axolotl (Ambystoma mexicanum is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum that typically undergo a metamorphosis. Results Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs were identified as unique to the axolotl (n = 76 and tiger salamander (n = 292 than were identified as shared (n = 108. All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times. Conclusions Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome

  7. Arsenic Induced Decreases in the Vascular Matrix

    OpenAIRE

    Hays, Allison M.; Lantz, R. Clark; Rodgers, Laurel S.; Sollome, James J.; Vaillancourt, Richard R.; Andrew, Angeline S; Hamilton, Joshua W.; Camenisch, Todd D.

    2008-01-01

    Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expres...

  8. Extensive Differences in Antifungal Immune Response in Two Drosophila Species Revealed by Comparative Transcriptome Analysis

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    Yosuke Seto

    2013-01-01

    Full Text Available The innate immune system of Drosophila is activated by ingestion of microorganisms. D. melanogaster breeds on fruits fermented by Saccharomyces cerevisiae, whereas D. virilis breeds on slime flux and decaying bark of tree housing a variety of bacteria, yeasts, and molds. In this study, it is shown that D. virilis has a higher resistance to oral infection of a species of filamentous fungi belonging to the genus Penicillium compared to D. melanogaster. In response to the fungal infection, a transcriptome profile of immune-related genes was considerably different between D. melanogaster and D. virilis: the genes encoding antifungal peptides, Drosomycin and Metchnikowin, were highly expressed in D. melanogaster whereas, the genes encoding Diptericin and Defensin were highly expressed in D. virilis. On the other hand, the immune-induced molecule (IM genes showed contrary expression patterns between the two species: they were induced by the fungal infection in D. melanogaster but tended to be suppressed in D. virilis. Our transcriptome analysis also showed newly predicted immune-related genes in D. virilis. These results suggest that the innate immune system has been extensively differentiated during the evolution of these Drosophila species.

  9. Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations of key functional networks.

    Science.gov (United States)

    Schiarea, Silvia; Solinas, Graziella; Allavena, Paola; Scigliuolo, Graziana Maria; Bagnati, Renzo; Fanelli, Roberto; Chiabrando, Chiara

    2010-09-01

    The cancer secretome is a rich repository in which to mine useful information for both cancer biology and clinical oncology. To help understand the mechanisms underlying the progression of pancreatic cancer, we characterized the secretomes of four human pancreatic ductal adenocarcinoma (PDAC) cell lines versus a normal counterpart. To this end, we used a proteomic workflow based on high-confidence protein identification by mass spectrometry, semiquantitation by a label-free approach, and network enrichment analysis by a system biology tool. Functional networks significantly enriched with PDAC-dysregulated proteins included not only expected alterations within key mechanisms known to be relevant for tumor progression (e.g., cell-cell/cell-matrix adhesion, extracellular matrix remodeling, and cytoskeleton rearrangement), but also other extensive, coordinated perturbations never observed in pancreatic cancer. In particular, we highlighted perturbations possibly favoring tumor progression through immune escape (i.e., inhibition of the complement system, deficiency of selected proteasome components within the antigen-presentation machinery, and inhibition of T cell cytoxicity), and a defective protein folding machinery. Among the proteins found concordantly oversecreted in all of our PDAC cell lines, many are reportedly overexpressed in pancreatic cancer (e.g., CD9 and Vimentin), while others (PLOD3, SH3L3, PCBP1, and SFRS1) represent novel PDAC-secreted proteins that may be worth investigating. PMID:20687567

  10. Proteomic analysis reveals key proteins and phosphoproteins upon seed germination of wheat (Triticum aestivum L.

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    Kun eDong

    2015-11-01

    Full Text Available Wheat (Triticum aestivum L. is one of the oldest cultivated crops and the second most important food crop in the world. Seed germination is the key developmental process in plant growth and development, and poor germination directly affects plant growth and subsequent grain yield. In this study, we performed the first dynamic proteome analysis of wheat seed germination using a two-dimensional differential gel electrophoresis (2D-DIGE-based proteomic approach. A total of 166 differentially expressed protein (DEP spots representing 73 unique proteins were identified, which are mainly involved in storage, stress/defense/detoxification, carbohydrate metabolism, photosynthesis, cell metabolism, and transcription/translation/ transposition. The identified DEPs and their dynamic expression profiles generally correspond to three distinct seed germination phases after imbibition: storage degradation, physiological processes/morphogenesis, and photosynthesis. Some key DEPs involved in storage substance degradation and plant defense mechanisms, such as globulin 3, sucrose synthase type I, serpin, beta-amylase, and plastid ADP-glucose pyrophosphorylase (AGPase small subunit, were found to be phosphorylated during seed germination. Particularly, the phosphorylation site Ser355 was found to be located in the enzyme active region of beta-amylase, which promotes substrate binding. Phosphorylated modification of several proteins could promote storage substance degradation and environmental stress defense during seed germination. The central metabolic pathways involved in wheat seed germination are proposed herein, providing new insights into the molecular mechanisms of cereal seed germination.

  11. Phylogenetic analysis reveals the global migration of seasonal influenza A viruses.

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    Martha I Nelson

    2007-09-01

    Full Text Available The winter seasonality of influenza A virus in temperate climates is one of the most widely recognized, yet least understood, epidemiological patterns in infectious disease. Central to understanding what drives the seasonal emergence of this important human pathogen is determining what becomes of the virus during the non-epidemic summer months. Herein, we take a step towards elucidating the seasonal emergence of influenza virus by determining the evolutionary relationship between populations of influenza A virus sampled from opposite hemispheres. We conducted a phylogenetic analysis of 487 complete genomes of human influenza A/H3N2 viruses collected between 1999 and 2005 from Australia and New Zealand in the southern hemisphere, and a representative sub-sample of viral genome sequences from 413 isolates collected in New York state, United States, representing the northern hemisphere. We show that even in areas as relatively geographically isolated as New Zealand's South Island and Western Australia, global viral migration contributes significantly to the seasonal emergence of influenza A epidemics, and that this migration has no clear directional pattern. These observations run counter to suggestions that local epidemics are triggered by the climate-driven reactivation of influenza viruses that remain latent within hosts between seasons or transmit at low efficiency between seasons. However, a complete understanding of the seasonal movements of influenza A virus will require greatly expanded global surveillance, particularly of tropical regions where the virus circulates year-round, and during non-epidemic periods in temperate climate areas.

  12. Revealing the X-ray Variability of AGN with Principal Component Analysis

    CERN Document Server

    Parker, M L; Matt, G; Koljonen, K I I; Kara, E; Alston, W; Walton, D J; Marinucci, A; Brenneman, L; Risaliti, G

    2014-01-01

    We analyse a sample of 26 active galactic nuclei with deep XMM-Newton observations, using principal component analysis (PCA) to find model independent spectra of the different variable components. In total, we identify at least 12 qualitatively different patterns of spectral variability, involving several different mechanisms, including five sources which show evidence of variable relativistic reflection (MCG-6-30-15, NGC 4051, 1H 0707-495, NGC 3516 and Mrk 766) and three which show evidence of varying partial covering neutral absorption (NGC 4395, NGC 1365, and NGC 4151). In over half of the sources studied, the variability is dominated by changes in a power law continuum, both in terms of changes in flux and power law index, which could be produced by propagating fluctuations within the corona. Simulations are used to find unique predictions for different physical models, and we then attempt to qualitatively match the results from the simulations to the behaviour observed in the real data. We are able to ex...

  13. Transcriptome analysis of the rhizosphere bacterium Azospirillum brasilense reveals an extensive auxin response.

    Science.gov (United States)

    Van Puyvelde, Sandra; Cloots, Lore; Engelen, Kristof; Das, Frederik; Marchal, Kathleen; Vanderleyden, Jos; Spaepen, Stijn

    2011-05-01

    The rhizosphere bacterium Azospirillum brasilense produces the auxin indole-3-acetic acid (IAA) through the indole-3-pyruvate pathway. As we previously demonstrated that transcription of the indole-3-pyruvate decarboxylase (ipdC) gene is positively regulated by IAA, produced by A. brasilense itself or added exogenously, we performed a microarray analysis to study the overall effects of IAA on the transcriptome of A. brasilense. The transcriptomes of A. brasilense wild-type and the ipdC knockout mutant, both cultured in the absence and presence of exogenously added IAA, were compared.Interfering with the IAA biosynthesis/homeostasis in A. brasilense through inactivation of the ipdC gene or IAA addition results in much broader transcriptional changes than anticipated. Based on the multitude of changes observed by comparing the different transcriptomes, we can conclude that IAA is a signaling molecule in A. brasilense. It appears that the bacterium, when exposed to IAA, adapts itself to the plant rhizosphere, by changing its arsenal of transport proteins and cell surface proteins. A striking example of adaptation to IAA exposure, as happens in the rhizosphere, is the upregulation of a type VI secretion system (T6SS) in the presence of IAA. The T6SS is described as specifically involved in bacterium-eukaryotic host interactions. Additionally, many transcription factors show an altered regulation as well, indicating that the regulatory machinery of the bacterium is changing.

  14. Cold tolerance in rice germinating seeds revealed by deep RNAseq analysis of contrasting indica genotypes.

    Science.gov (United States)

    Dametto, Andressa; Sperotto, Raul A; Adamski, Janete M; Blasi, Édina A R; Cargnelutti, Denise; de Oliveira, Luiz F V; Ricachenevsky, Felipe K; Fregonezi, Jeferson N; Mariath, Jorge E A; da Cruz, Renata P; Margis, Rogério; Fett, Janette P

    2015-09-01

    Rice productivity is largely affected by low temperature, which can be harmful throughout plant development, from germination to grain filling. Germination of indica rice cultivars under cold is slow and not uniform, resulting in irregular emergence and small plant population. To identify and characterize novel genes involved in cold tolerance during the germination stage, two indica rice genotypes (sister lines previously identified as cold-tolerant and cold-sensitive) were used in parallel transcriptomic analysis (RNAseq) under cold treatment (seeds germinating at 13 °C for 7 days). We detected 1,361 differentially expressed transcripts. Differences in gene expression found by RNAseq were confirmed for 11 selected genes using RT-qPCR. Biological processes enhanced in the cold-tolerant seedlings include: cell division and expansion (confirmed by anatomical sections of germinating seeds), cell wall integrity and extensibility, water uptake and membrane transport capacity, sucrose synthesis, generation of simple sugars, unsaturation of membrane fatty acids, wax biosynthesis, antioxidant capacity (confirmed by histochemical staining of H2O2), and hormone and Ca(2+)-signaling. The cold-sensitive seedlings respond to low temperature stress increasing synthesis of HSPs and dehydrins, along with enhanced ubiquitin/proteasome protein degradation pathway and polyamine biosynthesis. Our findings can be useful in future biotechnological approaches aiming to cold tolerance in indica rice. PMID:26259169

  15. Analysis of neural crest-derived clones reveals novel aspects of facial development.

    Science.gov (United States)

    Kaucka, Marketa; Ivashkin, Evgeny; Gyllborg, Daniel; Zikmund, Tomas; Tesarova, Marketa; Kaiser, Jozef; Xie, Meng; Petersen, Julian; Pachnis, Vassilis; Nicolis, Silvia K; Yu, Tian; Sharpe, Paul; Arenas, Ernest; Brismar, Hjalmar; Blom, Hans; Clevers, Hans; Suter, Ueli; Chagin, Andrei S; Fried, Kaj; Hellander, Andreas; Adameyko, Igor

    2016-08-01

    Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth. PMID:27493992

  16. Global Analysis of miRNA Gene Clusters and Gene Families Reveals Dynamic and Coordinated Expression

    Directory of Open Access Journals (Sweden)

    Li Guo

    2014-01-01

    Full Text Available To further understand the potential expression relationships of miRNAs in miRNA gene clusters and gene families, a global analysis was performed in 4 paired tumor (breast cancer and adjacent normal tissue samples using deep sequencing datasets. The compositions of miRNA gene clusters and families are not random, and clustered and homologous miRNAs may have close relationships with overlapped miRNA species. Members in the miRNA group always had various expression levels, and even some showed larger expression divergence. Despite the dynamic expression as well as individual difference, these miRNAs always indicated consistent or similar deregulation patterns. The consistent deregulation expression may contribute to dynamic and coordinated interaction between different miRNAs in regulatory network. Further, we found that those clustered or homologous miRNAs that were also identified as sense and antisense miRNAs showed larger expression divergence. miRNA gene clusters and families indicated important biological roles, and the specific distribution and expression further enrich and ensure the flexible and robust regulatory network.

  17. Breeding origin and migration pattern of dunlin (Calidris alpina) revealed by mitochondrial DNA analysis.

    Science.gov (United States)

    Wennerberg, L

    2001-05-01

    The large-scale migration of birds has been studied extensively by recoveries of ringed birds. However, there is very little ringing data from the arctic breeding grounds of waders. Here, the migration pattern of the dunlin, Calidris alpina, is studied with population genetic markers, using haplotype frequencies to estimate the breeding origin of migrating and wintering populations. Polymerase chain reaction (PCR) and restriction analysis of DNA from the mitochondrial control region was used to study the breeding origins of morphologically similar winter populations in the western Palaearctic, and to describe the population structure of the dunlin during winter. Also migrating dunlin from various stopover sites in Europe, Africa and Asia, were analysed with respect to their mitochondrial DNA (mtDNA) haplotypes. The genetic markers clearly show that the dunlin has a parallel migration system, with populations breeding in the western Palaearctic wintering mainly in the western part of the wintering range, and dunlin populations breeding further east wintering further east. The results also show that the distance between breeding and wintering area increases eastwards in this region. PMID:11380870

  18. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics.

    Science.gov (United States)

    Gatto, Francesco; Schulze, Almut; Nielsen, Jens

    2016-07-19

    Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network. PMID:27396332

  19. Starch grain analysis reveals function of grinding stone tools at Shangzhai site, Beijing

    Institute of Scientific and Technical Information of China (English)

    YANG XiaoYan; YU JinCheng; LI HouYuan; CUI TianXing; GUO JingNing; GE QuanSheng

    2009-01-01

    Prehistoric groundstone tools including slabs (metate, mo-pan) and mullers (mano, mo-bang) are often considered to be tools that were used to process cereals in ancient China. Most archaeologists believe that groundstone tools are indicators of an agrarian economy. This study employed starch grain analysis to examine a slab and a muller excavated from the Shangzhai Site (7500--7000 cal a BP), Beijing. Identifiable starch grains recovered from the stone tools were classified into 9 genera and 12 species, most of which were from acorns and foxtail millets. Remains from the oak species Q. mongolicus, Q. acuttssima, and Q. dentate were identified as well as a few starch grains from broomcorn (Panicum miliaseum) and bean (Vigna sp.). Other starch grains were from unidenUfiable roots and grasses. A variety of starch grains indicates that the grinding stone tools were used to process not only cereals, but also other seeds or roots that had to be ground or husked, thus bringing into question the aforementioned cereal hypothesis. Because the numbers of starch grains from nuts and millets were so large, both gathering and cultivation might have been important economic patterns before 7000 years ago in Beijing area. Moreover, the starch remains are derived from plants that indicate that the paleoclimate of Beijing was wetter and warmer than today's.

  20. The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis

    Science.gov (United States)

    Kinaston, Rebecca L.; Walter, Richard K.; Jacomb, Chris; Brooks, Emma; Tayles, Nancy; Halcrow, Sian E.; Stirling, Claudine; Reid, Malcolm; Gray, Andrew R.; Spinks, Jean; Shaw, Ben; Fyfe, Roger; Buckley, Hallie R.

    2013-01-01

    Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium) of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement. PMID:23691250

  1. The first New Zealanders: patterns of diet and mobility revealed through isotope analysis.

    Directory of Open Access Journals (Sweden)

    Rebecca L Kinaston

    Full Text Available Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement.

  2. Genome-wide analysis in Brazilian Xavante Indians reveals low degree of admixture.

    Directory of Open Access Journals (Sweden)

    Patricia C Kuhn

    Full Text Available Characterization of population genetic variation and structure can be used as tools for research in human genetics and population isolates are of great interest. The aim of the present study was to characterize the genetic structure of Xavante Indians and compare it with other populations. The Xavante, an indigenous population living in Brazilian Central Plateau, is one of the largest native groups in Brazil. A subset of 53 unrelated subjects was selected from the initial sample of 300 Xavante Indians. Using 86,197 markers, Xavante were compared with all populations of HapMap Phase III and HGDP-CEPH projects and with a Southeast Brazilian population sample to establish its population structure. Principal Components Analysis showed that the Xavante Indians are concentrated in the Amerindian axis near other populations of known Amerindian ancestry such as Karitiana, Pima, Surui and Maya and a low degree of genetic admixture was observed. This is consistent with the historical records of bottlenecks experience and cultural isolation. By calculating pair-wise F(st statistics we characterized the genetic differentiation between Xavante Indians and representative populations of the HapMap and from HGDP-CEPH project. We found that the genetic differentiation between Xavante Indians and populations of Ameridian, Asian, European, and African ancestry increased progressively. Our results indicate that the Xavante is a population that remained genetically isolated over the past decades and can offer advantages for genome-wide mapping studies of inherited disorders.

  3. Independent component analysis reveals new and biologically significant structures in micro array data

    Directory of Open Access Journals (Sweden)

    Veerla Srinivas

    2006-06-01

    Full Text Available Abstract Background An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. Results We applied independent component analysis (ICA to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. Conclusion Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.

  4. Starch grain analysis reveals function of grinding stone tools at Shangzhai site, Beijing

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Prehistoric groundstone tools including slabs (metate, mo-pan) and mullers (mano, mo-bang) are often considered to be tools that were used to process cereals in ancient China. Most archaeologists believe that groundstone tools are indicators of an agrarian economy. This study employed starch grain analysis to examine a slab and a muller excavated from the Shangzhai Site (7500-7000 cal a BP), Beijing. Identifiable starch grains recovered from the stone tools were classified into 9 genera and 12 species, most of which were from acorns and foxtail millets. Remains from the oak species Q. mongolicus, Q. acuttssima, and Q. dentate were identified as well as a few starch grains from broomcorn (Panicum miliaseum) and bean (Vigna sp.). Other starch grains were from unidentifiable roots and grasses. A variety of starch grains indicates that the grinding stone tools were used to process not only cereals, but also other seeds or roots that had to be ground or husked, thus bringing into question the aforementioned cereal hypothesis. Because the numbers of starch grains from nuts and millets were so large, both gathering and cultivation might have been important economic patterns before 7000 years ago in Beijing area. Moreover, the starch remains are derived from plants that indicate that the paleoclimate of Beijing was wetter and warmer than today’s.

  5. Biogeographic analysis reveals ancient continental vicariance and recent oceanic dispersal in amphibians.

    Science.gov (United States)

    Pyron, R Alexander

    2014-09-01

    Amphibia comprises over 7000 extant species distributed in almost every ecosystem on every continent except Antarctica. Most species also show high specificity for particular habitats, biomes, or climatic niches, seemingly rendering long-distance dispersal unlikely. Indeed, many lineages still seem to show the signature of their Pangaean origin, approximately 300 Ma later. To date, no study has attempted a large-scale historical-biogeographic analysis of the group to understand the distribution of extant lineages. Here, I use an updated chronogram containing 3309 species (∼ 45% of extant diversity) to reconstruct their movement between 12 global ecoregions. I find that Pangaean origin and subsequent Laurasian and Gondwanan fragmentation explain a large proportion of patterns in the distribution of extant species. However, dispersal during the Cenozoic, likely across land bridges or short distances across oceans, has also exerted a strong influence. Finally, there are at least three strongly supported instances of long-distance oceanic dispersal between former Gondwanan landmasses during the Cenozoic. Extinction from intervening areas seems to be a strong factor in shaping present-day distributions. Dispersal and extinction from and between ecoregions are apparently tied to the evolution of extraordinarily adaptive expansion-oriented phenotypes that allow lineages to easily colonize new areas and diversify, or conversely, to extremely specialized phenotypes or heavily relictual climatic niches that result in strong geographic localization and limited diversification.

  6. Heterogeneity among Mycobacterium ulcerans from French Guiana revealed by multilocus variable number tandem repeat analysis (MLVA).

    Science.gov (United States)

    Reynaud, Yann; Millet, Julie; Couvin, David; Rastogi, Nalin; Brown, Christopher; Couppié, Pierre; Legrand, Eric

    2015-01-01

    Buruli ulcer is an emerging and neglected tropical disease caused by Mycobacterium ulcerans. Few cases have been reported so far in the Americas. With 250 cases reported since 1969, French Guiana is the only Buruli ulcer endemic area in the continent. Thus far, no genetic diversity studies of strains of M. ulcerans from French Guiana have been reported. Our goal in the present study was to examine the genetic diversity of M. ulcerans strains in this region by using the Multilocus Variable Number Tandem Repeat Analysis (MLVA) approach. A total of 23 DNA samples were purified from ulcer biopsies or derived from pure cultures. MVLA was used in the study of six previously-described Variable Number of Tandem Repeat (VNTR) markers. A total of three allelic combinations were characterized in our study: genotype I which has been described previously, genotype III which is very similar to genotype I, and genotype II which has distinctly different characteristics in comparison with the other two genotypes. This high degree of genetic diversity appears to be uncommon for M. ulcerans. Further research based on complete genome sequencing of strains belonging to genotypes I and II is in progress and should lead soon to a better understanding of genetic specificities of M. ulcerans strains from French Guiana.

  7. Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

    Science.gov (United States)

    Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

    2015-12-01

    During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group.

  8. Transcriptomic analysis of Ustilago maydis infecting Arabidopsis reveals important aspects of the fungus pathogenic mechanisms.

    Science.gov (United States)

    Martínez-Soto, Domingo; Robledo-Briones, Angélica M; Estrada-Luna, Andrés A; Ruiz-Herrera, José

    2013-08-01

    Transcriptomic and biochemical analyses of the experimental pathosystem constituted by Ustilago maydis and Arabidopsis thaliana were performed. Haploid or diploid strains of U. maydis inoculated in A. thaliana plantlets grew on the surface and within the plant tissues in the form of mycelium, inducing chlorosis, anthocyanin formation, malformations, necrosis and adventitious roots development, but not teliospores. Symptoms were more severe in plants inoculated with the haploid strain which grew more vigorously than the diploid strain. RNA extracted at different times post-infection was used for hybridization of one-channel microarrays that were analyzed focusing on the fungal genes involved in the general pathogenic process, biogenesis of the fungal cell wall and the secretome. In total, 3,537 and 3,299 genes were differentially expressed in the haploid and diploid strains, respectively. Differentially expressed genes were related to different functional categories and many of them showed a similar regulation occurring in U. maydis infecting maize. Our data suggest that the haploid strain behaves as a necrotrophic pathogen, whereas the diploid behaves as a biotrophic pathogen. The results obtained are evidence of the usefulness of the U. maydis-A. thaliana pathosystem for the analysis of the pathogenic mechanisms of U. maydis.

  9. Wavelet analysis of corneal endothelial electrical potential difference reveals cyclic operation of the secretory mechanism

    CERN Document Server

    Cacace, Veronica Ines; Kusnier, Carlos; Gomez, Martin Pedro; Fischbarg, Jorge

    2011-01-01

    There is evidence that the electrical potential difference of corneal endothelium (TEPD) is related electro-osmotically to fluid transport. Hence, determination of the TEPD would serve as a measure of the fluid movement. The oscillatory nature of the TEPD has been recognized recently using the Fourier transform; the oscillations of the highest amplitude were linked to the operation of electrogenic sodium-bicarbonate cotransporters. However, no time localization of that activity could be obtained with the Fourier methodology utilized. For that reason we now characterize the TEPD using wavelet analysis for the first time in the epithelial physiology field, with the aim to localize in time the variations in TEPD. We find that the high-amplitude oscillations of the TEPD are cyclic, with a period of 4.6 \\pm 0.4 s in the average (n=4). The wavelet power value at the peak of such oscillations is 1.5 \\pm 0.1 mV2 Hz in the average (n=4), and is remarkably narrow in its distribution.

  10. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, Balaji [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Miles, Kenneth A.; Critchley, Hugo D. [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); Young, Rupert C.D.; Chatwin, Christopher R. [University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Gurling, Hugh M.D. [University College London, Department of Mental Health Sciences, London (United Kingdom)

    2010-04-15

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  11. Microarray Analysis Reveals the Molecular Basis of Antiarthritic Activity of Huo-Luo-Xiao-Ling Dan

    Directory of Open Access Journals (Sweden)

    Hua Yu

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC in the rat adjuvant arthritis (AA model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65, 84 differentially expressed genes (DEG (64 upregulated and 20 downregulated versus 120 DEG (94 upregulated and 26 downregulated were identified in HLXL-treated versus vehicle (Water-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.

  12. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

    Directory of Open Access Journals (Sweden)

    Francesco Gatto

    2016-07-01

    Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

  13. Peptide Vocabulary Analysis Reveals Ultra-Conservation and Homonymity in Protein Sequences

    Directory of Open Access Journals (Sweden)

    Derek Gatherer

    2007-01-01

    Full Text Available A new algorithm is presented for vocabulary analysis (word detection in texts of human origin. It performs at 60%–70% overall accuracy and greater than 80% accuracy for longer words, and approximately 85% sensitivity on Alice in Wonderland, a considerable improvement on previous methods. When applied to protein sequences, it detects short sequences analogous to words in human texts, i.e. intolerant to changes in spelling (mutation, and relatively contextindependent in their meaning (function. Some of these are homonyms of up to 7 amino acids, which can assume different structures in different proteins. Others are ultra-conserved stretches of up to 18 amino acids within proteins of less than 40% overall identity, reflecting extreme constraint or convergent evolution. Different species are found to have qualitatively different major peptide vocabularies, e.g. some are dominated by large gene families, while others are rich in simple repeats or dominated by internally repetitive proteins. This suggests the possibility of a peptide vocabulary signature, analogous to genome signatures in DNA. Homonyms may be useful in detecting convergent evolution and positive selection in protein evolution. Ultra-conserved words may be useful in identifying structures intolerant to substitution over long periods of evolutionary time.

  14. Extensive differences in antifungal immune response in two Drosophila species revealed by comparative transcriptome analysis.

    Science.gov (United States)

    Seto, Yosuke; Tamura, Koichiro

    2013-01-01

    The innate immune system of Drosophila is activated by ingestion of microorganisms. D. melanogaster breeds on fruits fermented by Saccharomyces cerevisiae, whereas D. virilis breeds on slime flux and decaying bark of tree housing a variety of bacteria, yeasts, and molds. In this study, it is shown that D. virilis has a higher resistance to oral infection of a species of filamentous fungi belonging to the genus Penicillium compared to D. melanogaster. In response to the fungal infection, a transcriptome profile of immune-related genes was considerably different between D. melanogaster and D. virilis: the genes encoding antifungal peptides, Drosomycin and Metchnikowin, were highly expressed in D. melanogaster whereas, the genes encoding Diptericin and Defensin were highly expressed in D. virilis. On the other hand, the immune-induced molecule (IM) genes showed contrary expression patterns between the two species: they were induced by the fungal infection in D. melanogaster but tended to be suppressed in D. virilis. Our transcriptome analysis also showed newly predicted immune-related genes in D. virilis. These results suggest that the innate immune system has been extensively differentiated during the evolution of these Drosophila species. PMID:24151578

  15. Comprehensive analysis reveals how single nucleotides contribute to noncoding RNA function in bacterial quorum sensing.

    Science.gov (United States)

    Rutherford, Steven T; Valastyan, Julie S; Taillefumier, Thibaud; Wingreen, Ned S; Bassler, Bonnie L

    2015-11-01

    Five homologous noncoding small RNAs (sRNAs), called the Qrr1-5 sRNAs, function in the Vibrio harveyi quorum-sensing cascade to drive its operation. Qrr1-5 use four different regulatory mechanisms to control the expression of ∼ 20 mRNA targets. Little is known about the roles individual nucleotides play in mRNA target selection, in determining regulatory mechanism, or in defining Qrr potency and dynamics of target regulation. To identify the nucleotides vital for Qrr function, we developed a method we call RSort-Seq that combines saturating mutagenesis, fluorescence-activated cell sorting, high-throughput sequencing, and mutual information theory to explore the role that every nucleotide in Qrr4 plays in regulation of two mRNA targets, luxR and luxO. Companion biochemical assays allowed us to assign specific regulatory functions/underlying molecular mechanisms to each important base. This strategy yielded a regional map of nucleotides in Qrr4 vital for stability, Hfq interaction, stem-loop formation, and base pairing to both luxR and luxO, to luxR only, and to luxO only. In terms of nucleotides critical for sRNA function, the RSort-Seq analysis provided strikingly different results from those predicted by commonly used regulatory RNA-folding algorithms. This approach is applicable to any RNA-RNA interaction, including sRNAs in other bacteria and regulatory RNAs in higher organisms.

  16. Revealing the metabonomic variation of rosemary extracts using 1H NMR spectroscopy and multivariate data analysis.

    Science.gov (United States)

    Xiao, Chaoni; Dai, Hui; Liu, Hongbing; Wang, Yulan; Tang, Huiru

    2008-11-12

    The molecular compositions of rosemary ( Rosmarinus officinalis L.) extracts and their dependence on extraction solvents, seasons, and drying processes were systematically characterized using NMR spectroscopy and multivariate data analysis. The results showed that the rosemary metabonome was dominated by 33 metabolites including sugars, amino acids, organic acids, polyphenolic acids, and diterpenes, among which quinate, cis-4-glucosyloxycinnamic acid, and 3,4,5-trimethoxyphenylmethanol were found in rosemary for the first time. Compared with water extracts, the 50% aqueous methanol extracts contained higher levels of sucrose, succinate, fumarate, malonate, shikimate, and phenolic acids, but lower levels of fructose, glucose, citrate, and quinate. Chloroform/methanol was an excellent solvent for selective extraction of diterpenes. From February to August, the levels of rosmarinate and quinate increased, whereas the sucrose level decreased. The sun-dried samples contained higher concentrations of rosmarinate, sucrose, and some amino acids but lower concentrations of glucose, fructose, malate, succinate, lactate, and quinate than freeze-dried ones. These findings will fill the gap in the understanding of rosemary composition and its variations.

  17. Genomic analysis of six new Geobacillus strains reveals highly conserved carbohydrate degradation architectures and strategies

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    Phillip eBrumm

    2015-05-01

    Full Text Available In this work we report the whole genome sequences of six new Geobacillus xylanolytic strains along with the genomic analysis of their capability to degrade carbohydrates.. The six sequenced Geobacillus strains described here have a range of GC contents from 43.9% to 52.5% and clade with named Geobacillus species throughout the entire genus. We have identified a ~200 kb unique super-cluster in all six strains, containing five to eight distinct carbohydrate degradation clusters in a single genomic region, a feature not seen in other genera. The Geobacillus strains rely on a small number of secreted enzymes located within distinct clusters for carbohydrate utilization, in contrast to most biomass-degrading organisms which contain numerous secreted enzymes located randomly throughout the genomes. All six strains are able to utilize fructose, arabinose, xylose, mannitol, gluconate, xylan, and α-1,6-glucosides. The gene clusters for utilization of these seven substrates have identical organization and the individual proteins have a high percent identity to their homologs. The strains show significant differences in their ability to utilize inositol, sucrose, lactose, α-mannosides, α-1,4-glucosides and arabinan.

  18. A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

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    Tao Wu

    2016-06-01

    Full Text Available Background/Aims: Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the “Li” aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Methods: Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Results: Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35, 1b (n=31, 3b (n=16, 2a (n=8, 3a (n=6, and 1a (n=4. By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Conclusions: Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention.

  19. Transcriptomic analysis reveals abnormal muscle repair and remodeling in survivors of critical illness with sustained weakness.

    Science.gov (United States)

    Walsh, Christopher J; Batt, Jane; Herridge, Margaret S; Mathur, Sunita; Bader, Gary D; Hu, Pingzhao; Dos Santos, Claudia C

    2016-01-01

    ICU acquired weakness (ICUAW) is a common complication of critical illness characterized by structural and functional impairment of skeletal muscle. The resulting physical impairment may persist for years after ICU discharge, with few patients regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW. PMID:27411715

  20. Comparative genomic sequence analysis of strawberry and other rosids reveals significant microsynteny

    Directory of Open Access Journals (Sweden)

    Abbott Albert

    2010-06-01

    Full Text Available Abstract Background Fragaria belongs to the Rosaceae, an economically important family that includes a number of important fruit producing genera such as Malus and Prunus. Using genomic sequences from 50 Fragaria fosmids, we have examined the microsynteny between Fragaria and other plant models. Results In more than half of the strawberry fosmids, we found syntenic regions that are conserved in Populus, Vitis, Medicago and/or Arabidopsis with Populus containing the greatest number of syntenic regions with Fragaria. The longest syntenic region was between LG VIII of the poplar genome and the strawberry fosmid 72E18, where seven out of twelve predicted genes were collinear. We also observed an unexpectedly high level of conserved synteny between Fragaria (rosid I and Vitis (basal rosid. One of the strawberry fosmids, 34E24, contained a cluster of R gene analogs (RGAs with NBS and LRR domains. We detected clusters of RGAs with high sequence similarity to those in 34E24 in all the genomes compared. In the phylogenetic tree we have generated, all the NBS-LRR genes grouped together with Arabidopsis CNL-A type NBS-LRR genes. The Fragaria RGA grouped together with those of Vitis and Populus in the phylogenetic tree. Conclusions Our analysis shows considerable microsynteny between Fragaria and other plant genomes such as Populus, Medicago, Vitis, and Arabidopsis to a lesser degree. We also detected a cluster of NBS-LRR type genes that are conserved in all the genomes compared.

  1. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies.

    Science.gov (United States)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-04-19

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

  2. Synergistic interaction between ankle and knee during hopping revealed through induced acceleration analysis.

    Science.gov (United States)

    João, Filipa; Veloso, António; Cabral, Sílvia; Moniz-Pereira, Vera; Kepple, Thomas

    2014-02-01

    The forces produced by the muscles can deliver energy to a target segment they are not attached to, by transferring this energy throughout the other segments in the chain. This is a synergistic way of functioning, which allows muscles to accelerate or decelerate segments in order to reach the target one. The purpose of this study was to characterize the contribution of each lower extremity joint to the vertical acceleration of the body's center of mass during a hopping exercise. To accomplish this, an induced acceleration analysis was performed using a model with eight segments. The results indicate that the strategies produced during a hopping exercise rely on the synergy between the knee and ankle joints, with most of the vertical acceleration being produced by the knee extensors, while the ankle plantar flexors act as stabilizers of the foot. This synergy between the ankle and the knee is perhaps a mechanism that allows the transfer of power from the knee muscles to the ground, and we believe that in this particular task the net action of the foot and ankle moments is to produce a stable foot with little overall acceleration.

  3. Proteomics Analysis Reveals Post-Translational Mechanisms for Cold-Induced Metabolic Changes in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Tian Li; Alma L.Burlingame; Zhi-Ping Deng; Zhi Yong Wang; Shou-Ling Xu; Juan A.Oses-Prieto; Sunita Putil; Peng Xu; Rui-Ju Wang; Kathy H.Li; David A.Malty; Liz-He An

    2011-01-01

    Cold-induced changes of gene expression and metabolism are critical for plants to survive freezing. Largely by changing gene expression, exposure to a period of non-freezing low temperatures increases plant tolerance to freezing-a phenomenon known as cold acclimation. Cold also induces rapid metabolic changes, which provide instant protection before temperature drops below freezing point. The molecular mechanisms for such rapid metabolic responses to cold remain largely unknown. Here, we use two-dimensional difference gel electrophoresis (2-D DIGE) analysis of sub-cellular fractions of Arabidopsis thaliana proteome coupled with spot identification by tandem mass spectrometry to identify early cold-responsive proteins in Arabidopsis. These proteins include four enzymes involved in starch degradation, three HSP100 proteins, several proteins in the tricarboxylic acid cycle, and sucrose metabolism. Upon cold treatment, the Disproportionating Enzyme 2 (DPE2), a cytosolic transglucosidase metabolizing maltose to glucose, increased rapidly in the centrifugation pellet fraction and decreased in the soluble fraction. Consistent with cold-induced inactivation of DPE2 enzymatic activity, the dpe2 mutant showed increased freezing tolerance without affecting the C-repeat binding transcription factor (CBF) transcriptional pathway. These results support a model that cold-induced inactivation of DPE2 leads to rapid accumulation of maltose, which is a cold-induced compatible solute that protects cells from freezing damage. This study provides evidence for a key role of rapid post-translational regulation of carbohydrate metabolic enzymes in plant protection against sudden temperature drop.

  4. Transcriptional analysis of Deinococcus radiodurans reveals novel small RNAs that are differentially expressed under ionizing radiation.

    Science.gov (United States)

    Tsai, Chen-Hsun; Liao, Rick; Chou, Brendan; Contreras, Lydia M

    2015-03-01

    Small noncoding RNAs (sRNAs) are posttranscriptional regulators that have been identified in multiple species and shown to play essential roles in responsive mechanisms to environmental stresses. The natural ability of specific bacteria to resist high levels of radiation has been of high interest to mechanistic studies of DNA repair and biomolecular protection. Deinococcus radiodurans is a model extremophile for radiation studies that can survive doses of ionizing radiation of >12,000 Gy, 3,000 times higher than for most vertebrates. Few studies have investigated posttranscriptional regulatory mechanisms of this organism that could be relevant in its general gene regulatory patterns. In this study, we identified 199 potential sRNA candidates in D. radiodurans by whole-transcriptome deep sequencing analysis and confirmed the expression of 41 sRNAs by Northern blotting and reverse transcriptase PCR (RT-PCR). A total of 8 confirmed sRNAs showed differential expression during recovery after acute ionizing radiation (15 kGy). We have also found and confirmed 7 sRNAs in Deinococcus geothermalis, a closely related radioresistant species. The identification of several novel sRNAs in Deinococcus bacteria raises important questions about the evolution and nature of global gene regulation in radioresistance.

  5. Network-Based Analysis Reveals Functional Connectivity Related to Internet Addiction Tendency.

    Science.gov (United States)

    Wen, Tanya; Hsieh, Shulan

    2016-01-01

    Preoccupation and compulsive use of the internet can have negative psychological effects, such that it is increasingly being recognized as a mental disorder. The present study employed network-based statistics to explore how whole-brain functional connections at rest is related to the extent of individual's level of internet addiction, indexed by a self-rated questionnaire. We identified two topologically significant networks, one with connections that are positively correlated with internet addiction tendency, and one with connections negatively correlated with internet addiction tendency. The two networks are interconnected mostly at frontal regions, which might reflect alterations in the frontal region for different aspects of cognitive control (i.e., for control of internet usage and gaming skills). Next, we categorized the brain into several large regional subgroupings, and found that the majority of proportions of connections in the two networks correspond to the cerebellar model of addiction which encompasses the four-circuit model. Lastly, we observed that the brain regions with the most inter-regional connections associated with internet addiction tendency replicate those often seen in addiction literature, and is corroborated by our meta-analysis of internet addiction studies. This research provides a better understanding of large-scale networks involved in internet addiction tendency and shows that pre-clinical levels of internet addiction are associated with similar regions and connections as clinical cases of addiction. PMID:26869896

  6. Metagenomic analysis reveals potential biodegradation pathways of persistent pesticides in freshwater and marine sediments.

    Science.gov (United States)

    Fang, Hua; Cai, Lin; Yang, Ying; Ju, Feng; Li, Xiangdong; Yu, Yunlong; Zhang, Tong

    2014-02-01

    The abundance and diversity of biodegradation genes (BDGs) and potential degradation pathways of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), and atrazine (ATZ) in freshwater and marine sediments were investigated by metagenomic analysis using 6 datasets (16Gb in total). The datasets were derived using Illumina high-throughput sequencing and were based on BLAST against self-established databases of BDGs, DDT degradation genes (DDGs), HCH degradation genes (HDGs), and ATZ degradation genes (ADGs). The results showed that the abundance and diversity of BDGs, DDGs, HDGs, and ADGs varied with sample source and locations. The lip and mnp genes, which encode for peroxidase, and the carA gene, which encodes for laccase, were detected as the dominant genes for degradation of organic pollutants. The hdt, hdg, and atzB genes, which encode for hydratase, dehalogenase, and ethylaminohydrolase, were found to be the most abundant genes involved in DDT, HCH, and ATZ degradation, respectively. The identified 69 genera capable of degrading organic pollutants were mostly affiliated with Proteobacteria (49.3%) and Actinobacteria (21.7%). Four genera, including Plesiocystis, Anaerolinea, Jannaschia, and Mycobacterium, were the major biodegradation populations in all sediments. In this study, the nearly complete biodegradation pathways of DDT and ATZ were found, and the partial degradation pathway of HCH was detected in all sediments.

  7. Salt-responsive genes in rice revealed by cDNA microarray analysis

    Institute of Scientific and Technical Information of China (English)

    Dai Yin CHAO; Yong Hai LUO; Min SHI; Da LUO; Hong Xuan LIN

    2005-01-01

    We used cDNA microarrays containing ~9,000 unigenes to identify 486 salt responsive expressed sequence tags (ESTs) (representing ~450 unigenes) in shoots of the highly salt-tolerant rice variety, Nona Bokra (Oryza sativa L. Ssp.Indica pv. Nona). Some of the genes identified in this study had previously been associated with salt stress. Howeverthe majority were novel, indicating that there is a great number of genes that are induced by salt exposure. Analysis of the salt stress expression profile data of Nona provided clues regarding some putative cellular and molecular processes that are undertaken by this tolerant rice variety in response to salt stress. Namely, we found that multiple transcription factors were induced during the initial salt response of shoots. Many genes whose encoded proteins are implicated in detoxification, protectant and transport were rapidly induced. Genes supporting photosynthesis were repressed and those supporting carbohydrate metabolism were altered. Commonality among the genes induced by salt exposure with those induced during senescence and biotic stress responses suggests that there are shared signaling pathways among these processes. We further compared the transcriptome changes of the salt-sensitive cultivar, IR28, with that of Nona rice. Many genes that are salt responsive in Nona were found to be differentially regulated in IR28. This study identified a large number of candidate functional genes that appear to be involved in salt tolerance and further examination of these genes may enable the molecular basis of salt tolerance to be elucidated.

  8. Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Jinling Wang

    2014-09-01

    Full Text Available Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

  9. A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

    Science.gov (United States)

    Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

    2015-08-01

    In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. PMID:26153924

  10. Complex history of admixture during citrus domestication revealed by genome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, G. Albert; Prochnik, Simon; Jenkins, Jerry; Salse, Jerome; Hellsten, Uffe; Murat, Florent; Perrier, Xavier; Ruiz, Manuel; Scalabrin, Simone; Terol, Javier; Takita, Marco Aur& #233; lio,; Labadie, Karine; Poulain, Julie; Couloux, Arnaud; Jabbari, Kamel; Cattonaro, Federica; Fabbro, Cristian Del; Pinosio, Sara; Zuccolo, Andrea; Chapman, Jarrod; Grimwood, Jane; Tadeo, Francisco; Estornell, Leandro H.; Mu?oz-Sanz, Juan V.; Ibanez, Victoria; Herrero-Ortega, Amparo; Aleza, Pablo; P& #233; rez, Juli& #225; n P& #233; rez,; Ramon, Daniel; Brunel, Dominique; Luro, Francois; Chen, Chunxian; Farmerie, William G.; Desany, Brian; Kodira, Chinnappa; Mohiuddin, Mohammed; Harkins, Tim; Fredrikson, Karin; Burns, Paul; Lomsadze, Alexandre; Borodovsky, Mark; Reforgiato, Giuseppe; Freitas-Astua, Juliana; Quetier, Francis; Navarro, Luis; Roose, Mikeal; Wincker, Patrick; Schmutz, Jeremy; Morgante, Michele; Machado, Marcos Antonio; Talon, Manuel; Jaillon, Olivier; Ollitrault, Patrick; Gmitter, Frederick; Rokhsar, Daniel

    2014-06-30

    Although Citrus is the most globally significant tree fruit, its domestication history is poorly understood. Cultivated citrus types are believed to comprise selections from and/or hybrids of several wild progenitor species, but the identities of these progenitors, and their contribution to modern cultivars, remain controversial. Here we report the genomes of a collection of mandarins, pummelos, and oranges, including a high quality reference sequence from a haploid Clementine mandarin. By comparative genome analysis we show that these cultivated types can be derived from two progenitor species. Cultivated pummelos represent selections from a single progenitor species C. maxima. Unexpectedly, however, we find that cultivated mandarins are introgressions of C. maxima into a distinct second population that we identify with the ancestral wild mandarin species C. reticulata. Sweet and sour oranges are found to be interspecific hybrids. Sweet orange, the most widely cultivated citrus, arose as the offspring of previously admixed individuals. In contrast, sour (or Seville) orange is an F1 hybrid of pure C. maxima and C. reticulata parents, implying that wild mandarins were part of the early breeding germplasm. Surprisingly, we also find that a wild Chinese mandarin from Mangshan, China shows substantial sequence divergence from C. reticulata and appears to represent a distinct taxon. Understanding the relationships and phylogeny of cultivated citrus through genome analysis will clarify taxonomic relationships and enable previously inconceivable opportunities for sequence-directed genetic improvement. Citrus are widely consumed worldwide as juice or fresh fruit, providing important sources of vitamin C and other health-promoting compounds. Global production in 2012 exceeded 86 million metric tons, with an estimated value of US$9 billion (http://www.fas.usda.gov/psdonline/circulars/citrus.pdf). The very narrow genetic diversity of cultivated citrus makes it highly

  11. Fine-scale analysis reveals cryptic landscape genetic structure in desert tortoises.

    Directory of Open Access Journals (Sweden)

    Emily K Latch

    Full Text Available Characterizing the effects of landscape features on genetic variation is essential for understanding how landscapes shape patterns of gene flow and spatial genetic structure of populations. Most landscape genetics studies have focused on patterns of gene flow at a regional scale. However, the genetic structure of populations at a local scale may be influenced by a unique suite of landscape variables that have little bearing on connectivity patterns observed at broader spatial scales. We investigated fine-scale spatial patterns of genetic variation and gene flow in relation to features of the landscape in desert tortoise (Gopherus agassizii, using 859 tortoises genotyped at 16 microsatellite loci with associated data on geographic location, sex, elevation, slope, and soil type, and spatial relationship to putative barriers (power lines, roads. We used spatially explicit and non-explicit Bayesian clustering algorithms to partition the sample into discrete clusters, and characterize the relationships between genetic distance and ecological variables to identify factors with the greatest influence on gene flow at a local scale. Desert tortoises exhibit weak genetic structure at a local scale, and we identified two subpopulations across the study area. Although genetic differentiation between the subpopulations was low, our landscape genetic analysis identified both natural (slope and anthropogenic (roads landscape variables that have significantly influenced gene flow within this local population. We show that desert tortoise movements at a local scale are influenced by features of the landscape, and that these features are different than those that influence gene flow at larger scales. Our findings are important for desert tortoise conservation and management, particularly in light of recent translocation efforts in the region. More generally, our results indicate that recent landscape changes can affect gene flow at a local scale and that their

  12. Fluctuation Analysis of Centrosomes Reveals a Cortical Function of Kinesin-1.

    Science.gov (United States)

    Winkler, Franziska; Gummalla, Maheshwar; Künneke, Lutz; Lv, Zhiyi; Zippelius, Annette; Aspelmeier, Timo; Grosshans, Jörg

    2015-09-01

    The actin and microtubule networks form the dynamic cytoskeleton. Network dynamics is driven by molecular motors applying force onto the networks and the interactions between the networks. Here we assay the dynamics of centrosomes in the scale of seconds as a proxy for the movement of microtubule asters. With this assay we want to detect the role of specific motors and of network interaction. During interphase of syncytial embryos of Drosophila, cortical actin and the microtubule network depend on each other. Centrosomes induce cortical actin to form caps, whereas F-actin anchors microtubules to the cortex. In addition, lateral interactions between microtubule asters are assumed to be important for regular spatial organization of the syncytial embryo. The functional interaction between the microtubule asters and cortical actin has been largely analyzed in a static manner, so far. We recorded the movement of centrosomes at 1 Hz and analyzed their fluctuations for two processes—pair separation and individual movement. We found that F-actin is required for directional movements during initial centrosome pair separation, because separation proceeds in a diffusive manner in latrunculin-injected embryos. For assaying individual movement, we established a fluctuation parameter as the deviation from temporally and spatially slowly varying drift movements. By analysis of mutant and drug-injected embryos, we found that the fluctuations were suppressed by both cortical actin and microtubules. Surprisingly, the microtubule motor Kinesin-1 also suppressed fluctuations to a similar degree as F-actin. Kinesin-1 may mediate linkage of the microtubule (+)-ends to the actin cortex. Consistent with this model is our finding that Kinesin-1-GFP accumulates at the cortical actin caps. PMID:26331244

  13. Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Zhang, Yi; Chrisler, William B.; Ewald, Jonathan A.; Wiley, H. S.; Resat, Haluk

    2012-10-02

    The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases, and controls a diverse set of cellular responses relevant to development and tumorigenesis. ErbB activation is a complex process involving receptor-ligand binding, receptor dimerization, phosphorylation, and trafficking (internalization, recycling and degradation), which together dictate the spatio-temporal distribution of active receptors within the cell. The ability to predict this distribution, and elucidation of the factors regulating it, would help to establish a mechanistic link between ErbB expression levels and the cellular response. Towards this end, we constructed mathematical models for deconvolving the contributions of receptor dimerization and phosphorylation to EGFR activation, and to examine the dependence of these processes on sub-cellular location. We collected experimental datasets for EGFR activation dynamics in human mammary epithelial cells, with the specific goal of model parameterization, and used the data to estimate parameters for several alternate models. Model-based analysis indicated that: 1) signal termination via receptor dephosphorylation in late endosomes, prior to degradation, is an important component of the response, 2) less than 40% of the receptors in the cell are phosphorylated at any given time, even at saturating ligand doses, and 3) receptor dephosphorylation rates at the cell surface and early endosomes are comparable. We validated the last finding by measuring EGFR dephosphorylation rates at various times following ligand addition both in whole cells, and in endosomes using ELISAs and fluorescent imaging. Overall, our results provide important information on how EGFR phosphorylation levels are regulated within cells. Further, the mathematical model described here can be extended to determine receptor dimer abundances in cells co-expressing various levels of ErbB receptors. This study demonstrates that an iterative cycle of

  14. A bout analysis reveals age-related methylmercury neurotoxicity and nimodipine neuroprotection.

    Science.gov (United States)

    Shen, Andrew Nathanael; Cummings, Craig; Pope, Derek; Hoffman, Daniel; Newland, M Christopher

    2016-09-15

    Age-related deficits in motor and cognitive functioning may be driven by perturbations in calcium (Ca(2+)) homeostasis in nerve terminals, mechanisms that are also thought to mediate the neurotoxicity of methylmercury (MeHg). Calcium-channel blockers (CCBs) protect against MeHg toxicity in adult mice, but little is known about their efficacy in other age groups. Two age groups of BALB/c mice were exposed to 0 or 1.2mg/kg/day MeHg and 0 or 20mg/kg/day of the CCB nimodipine for approximately 8.5 months. Adults began exposure on postnatal day (PND) 72 and the retired breeders on PND 296. High-rate operant behavior was maintained under a percentile schedule, which helped to decouple response rate from reinforcer rate. Responding was analyzed using a log-survivor bout analysis approach that partitioned behavior into high-rate bouts separated by pauses. MeHg-induced mortality did not depend on age but nimodipine neuroprotection was age-dependent, with poorer protection occurring in older mice. Within-bout response rate (a marker of sensorimotor function) was more sensitive to MeHg toxicity than bout-initiation rate (a marker of motivation). Within-bout rate declined almost 2 months prior to overt signs of toxicity for the MeHg-only retired breeders but not adults, suggesting greater delay to toxicity in younger animals. Motor-based decrements also appeared in relatively healthy adult MeHg+NIM animals. Aging appeared to alter the processes underlying Ca(2+) homeostasis thereby diminishing protection by nimodipine, even in mice that have not reached senescence. The study of MeHg exposure presents an experimental model by which to study potential mechanisms of aging. PMID:27196441

  15. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Helen L Hellmich

    Full Text Available Developing new pharmacotherapies for traumatic brain injury (TBI requires elucidation of the neuroprotective mechanisms of many structurally and functionally diverse compounds. To test our hypothesis that diverse neuroprotective drugs similarly affect common gene targets after TBI, we compared the effects of two drugs, metyrapone (MT and carbenoxolone (CB, which, though used clinically for noncognitive conditions, improved learning and memory in rats and humans. Although structurally different, both MT and CB inhibit a common molecular target, 11β hydroxysteroid dehydrogenase type 1, which converts inactive cortisone to cortisol, thereby effectively reducing glucocorticoid levels. We examined injury-induced signaling pathways to determine how the effects of these two compounds correlate with pro-survival effects in surviving neurons of the injured rat hippocampus. We found that treatment of TBI rats with MT or CB acutely induced in hippocampal neurons transcriptional profiles that were remarkably similar (i.e., a coordinated attenuation of gene expression across multiple injury-induced cell signaling networks. We also found, to a lesser extent, a coordinated increase in cell survival signals. Analysis of injury-induced gene expression altered by MT and CB provided additional insight into the protective effects of each. Both drugs attenuated expression of genes in the apoptosis, death receptor and stress signaling pathways, as well as multiple genes in the oxidative phosphorylation pathway such as subunits of NADH dehydrogenase (Complex1, cytochrome c oxidase (Complex IV and ATP synthase (Complex V. This suggests an overall inhibition of mitochondrial function. Complex 1 is the primary source of reactive oxygen species in the mitochondrial oxidative phosphorylation pathway, thus linking the protective effects of these drugs to a reduction in oxidative stress. The net effect of the drug-induced transcriptional changes observed here indicates that

  16. Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks.

    Directory of Open Access Journals (Sweden)

    Anderson Messias Rodrigues

    Full Text Available Sporothrix schenckii, previously assumed to be the sole agent of human and animal sporotrichosis, is in fact a species complex. Recently recognized taxa include S. brasiliensis, S. globosa, S. mexicana, and S. luriei, in addition to S. schenckii sensu stricto. Over the last decades, large epidemics of sporotrichosis occurred in Brazil due to zoonotic transmission, and cats were pointed out as key susceptible hosts. In order to understand the eco-epidemiology of feline sporotrichosis and its role in human sporotrichosis a survey was conducted among symptomatic cats. Prevalence and phylogenetic relationships among feline Sporothrix species were investigated by reconstructing their phylogenetic origin using the calmodulin (CAL and the translation elongation factor-1 alpha (EF1α loci in strains originated from Rio de Janeiro (RJ, n = 15, Rio Grande do Sul (RS, n = 10, Paraná (PR, n = 4, São Paulo (SP, n =3 and Minas Gerais (MG, n = 1. Our results showed that S. brasiliensis is highly prevalent among cats (96.9% with sporotrichosis, while S. schenckii was identified only once. The genotype of Sporothrix from cats was found identical to S. brasiliensis from human sources confirming that the disease is transmitted by cats. Sporothrix brasiliensis presented low genetic diversity compared to its sister taxon S. schenckii. No evidence of recombination in S. brasiliensis was found by split decomposition or PHI-test analysis, suggesting that S. brasiliensis is a clonal species. Strains recovered in states SP, MG and PR share the genotype of the RJ outbreak, different from the RS clone. The occurrence of separate genotypes among strains indicated that the Brazilian S. brasiliensis epidemic has at least two distinct sources. We suggest that cats represent a major host and the main source of cat and human S. brasiliensis infections in Brazil.

  17. Ancestry analysis reveals a predominant Native American component with moderate European admixture in Bolivians.

    Science.gov (United States)

    Heinz, Tanja; Alvarez-Iglesias, Vanesa; Pardo-Seco, Jacobo; Taboada-Echalar, Patricia; Gómez-Carballa, Alberto; Torres-Balanza, Antonio; Rocabado, Omar; Carracedo, Angel; Vullo, Carlos; Salas, Antonio

    2013-09-01

    We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas.

  18. PTT analysis of polyps from FAP patients reveals a great majority of APC truncating mutations

    Energy Technology Data Exchange (ETDEWEB)

    Luijt, R.B. van der; Khan, P.M.; Tops, C.M.J. [Leiden Univ., (Netherlands)] [and others

    1994-09-01

    The adenomatous polyposis coli (APC) gene plays an important role in colorectal carcinogenesis. Germline APC mutations are associated with familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer, characterized by the development of numerous adenomatous polyps in the large intestine. In order to investigate whether somatic inactivation of the remaining APC allele is necessary for adenoma formation, we collected multiple adenomatous polyps from individual FAP patients and investigated the presence of somatic mutations in the APC gene. The analysis of somatic APC mutations in these tumor samples was performed using a rapid and sensitive assay, called the protein truncation test (PTT). Chain-terminating somatic APC mutations were detected in the great majority of the tumor samples investigated. As expected, these mutations were mainly located in the mutation cluster region (MCR) in exon 15. Our results confirm that somatic mutation of the second APC allele is required for adenoma formation in FAP. Interestingly, in the polyps investigated in our study, the second APC allele is somatically inactivated through point mutation leading to a stop codon rather than by loss of heterozygosity. The observation that somatic second hits in APC are required for tumor development in FAP is in apparent accordance with the Knudson hypothesis for classical tumor suppressor genes. However, it is yet unknown whether chain-terminating APC mutations lead to a truncated protein exerting a dominant-negative effect or whether these mutations result in a null allele. Further investigation of this important issue will hopefully provide a better understanding of the mechanism of action of the mutated APC alleles in colorectal carcinogenesis.

  19. Anatomical and biochemical analysis reveal the role of anthocyanins in flower coloration of herbaceous peony.

    Science.gov (United States)

    Zhao, Da-Qiu; Wei, Meng-Ran; Liu, Ding; Tao, Jun

    2016-05-01

    Herbaceous peony (Paeonia lactiflora Pall.) is particularly appreciated because of its elegant and gorgeous flower color, but little is known about the underlying mechanisms of flower coloration. In this study, three P. lactiflora cultivars 'Xuefeng', 'Fenyulou' and 'Dahonglou' with white, pink and red flower were selected as the materials. Their anatomical structures, cell sap pH and metal elements were investigated, and the colored pigment mainly distributed in palisade mesophyll was only found in 'Fenyulou' and 'Dahonglou', and their shape of epidermal cells, cell sap pH and metal elements were not the key factors deciding phenotype color. Moreover, the qualitative and quantitative analysis of flavonoids were performed, their total anthocyanin, anthoxanthin and flavonoid contents were decreased during flower development, and only anthocyanin content in 'Dahonglou' was always higher than that in 'Xuefeng' and 'Fenyulou'. Subsequently, three anthocyanin compositions were found, and peonidin 3,5-di-O-glucoside (Pn3G5G) was identified as the main anthocyanin composition. In addition, the full-length of flavonol synthase gene (FLS) was isolated with the GenBank accession number KM259902, and the expression patterns of eight flavonoid biosynthetic genes showed that only PlDFR and PlANS basically had the highest levels in 'Dahonglou' and the lowest levels in 'Xuefeng', and they basically displayed a descended trend during flower development especially PlDFR, suggesting that these two genes might play a key role in the anthocyanin biosynthesis which resulted in the shift from white to pink and red in flowers. These results would contribute to understand the underlying molecular mechanisms of flower coloration in P. lactiflora.

  20. Genome-wide analysis reveals selection for important traits in domestic horse breeds.

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    Jessica L Petersen

    Full Text Available Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3. The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

  1. Balkanized Research in Ecological Engineering Revealed by a Bibliometric Analysis of Earthworms and Ecosystem Services

    Science.gov (United States)

    Blouin, Manuel; Sery, Nicolas; Cluzeau, Daniel; Brun, Jean-Jacques; Bédécarrats, Alain

    2013-08-01

    Energy crisis, climate changes, and biodiversity losses have reinforced the drive for more ecologically-based approaches for environmental management. Such approaches are characterized by the use of organisms rather than energy-consuming technologies. Although earthworms are believed to be potentially useful organisms for managing ecosystem services, there is actually no quantification of such a trend in literature. This bibliometric analysis aimed to measure the evolution of the association of "earthworms" and other terms such as ecosystem services (primary production, nutrient cycling, carbon sequestration, soil structure, and pollution remediation), "ecological engineering" or "biodiversity," to assess their convergence or divergence through time. In this aim, we calculated the similarity index, an indicator of the paradigmatic proximity defined in applied epistemology, for each year between 1900 and 2009. We documented the scientific fields and the geographical origins of the studies, as well as the land uses, and compare these characteristics with a 25 years old review on earthworm management. The association of earthworm related keywords with ecosystem services related keywords was increasing with time, reflecting the growing interest in earthworm use in biodiversity and ecosystem services management. Conversely, no significant increase in the association between earthworms and disciplines such as ecological engineering or restoration ecology was observed. This demonstrated that general ecologically-based approaches have yet to emerge and that there is little exchange of knowledge, methods or concepts among balkanized application realms. Nevertheless, there is a strong need for crossing the frontiers between fields of application and for developing an umbrella discipline to provide a framework for the use of organisms to manage ecosystem services.

  2. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.

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    Kenneth A Stapleford

    2016-01-01

    Full Text Available Chikungunya virus (CHIKV, an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak.We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR structure, not previously found in nature, that led to increased replication in insect cells.Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV.

  3. Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

    Science.gov (United States)

    Petersen, Jessica L.; Mickelson, James R.; Rendahl, Aaron K.; Valberg, Stephanie J.; Andersson, Lisa S.; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M.; Borges, Alexandre S.; Brama, Pieter; da Câmara Machado, Artur; Capomaccio, Stefano; Cappelli, Katia; Cothran, E. Gus; Distl, Ottmar; Fox-Clipsham, Laura; Graves, Kathryn T.; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A.; Mikko, Sofia; Orr, Nicholas; Penedo, M. Cecilia T.; Piercy, Richard J.; Raekallio, Marja; Rieder, Stefan; Røed, Knut H.; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; Wade, Claire M.; McCue, Molly E.

    2013-01-01

    Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. PMID:23349635

  4. Stable Isotope Analysis Reveals That Agricultural Habitat Provides an Important Dietary Component for Nonbreeding Dunlin

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    Lesley Joan Evans Ogden

    2005-12-01

    Full Text Available Although shorebirds spending the winter in temperate areas frequently use estuarine and supratidal (upland feeding habitats, the relative contribution of each habitat to individual diets has not been directly quantified. We quantified the proportional use that Calidris alpina pacifica (Dunlin made of estuarine vs. terrestrial farmland resources on the Fraser River Delta, British Columbia, using stable isotope analysis (δ13C, δ15N of blood from 268 Dunlin over four winters, 1997 through 2000. We tested for individual, age, sex, morphological, seasonal, and weather-related differences in dietary sources. Based on single- (δ13C and dual-isotope mixing models, the agricultural habitat contributed approximately 38% of Dunlin diet averaged over four winters, with the balance from intertidal flats. However, there was a wide variation among individuals in the extent of agricultural feeding, ranging from about 1% to 95% of diet. Younger birds had a significantly higher terrestrial contribution to diet (43% than did adults (35%. We estimated that 6% of adults and 13% of juveniles were obtaining at least 75% of their diet from terrestrial sources. The isotope data provided no evidence for sex or overall body size effects on the proportion of diet that is terrestrial in origin. The use of agricultural habitat by Dunlin peaked in early January. Adult Dunlin obtained a greater proportion of their diet terrestrially during periods of lower temperatures and high precipitation, whereas no such relationship existed for juveniles. Seasonal variation in the use of agricultural habitat suggests that it is used more during energetically stressful periods. The terrestrial farmland zone appears to be consistently important as a habitat for juveniles, but for adults it may provide an alternative feeding site used as a buffer against starvation during periods of extreme weather. Loss or reduction of agricultural habitat adjacent to estuaries may negatively impact

  5. Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks.

    Science.gov (United States)

    Rodrigues, Anderson Messias; de Melo Teixeira, Marcus; de Hoog, G Sybren; Schubach, Tânia Maria Pacheco; Pereira, Sandro Antonio; Fernandes, Geisa Ferreira; Bezerra, Leila Maria Lopes; Felipe, Maria Sueli; de Camargo, Zoilo Pires

    2013-01-01

    Sporothrix schenckii, previously assumed to be the sole agent of human and animal sporotrichosis, is in fact a species complex. Recently recognized taxa include S. brasiliensis, S. globosa, S. mexicana, and S. luriei, in addition to S. schenckii sensu stricto. Over the last decades, large epidemics of sporotrichosis occurred in Brazil due to zoonotic transmission, and cats were pointed out as key susceptible hosts. In order to understand the eco-epidemiology of feline sporotrichosis and its role in human sporotrichosis a survey was conducted among symptomatic cats. Prevalence and phylogenetic relationships among feline Sporothrix species were investigated by reconstructing their phylogenetic origin using the calmodulin (CAL) and the translation elongation factor-1 alpha (EF1α) loci in strains originated from Rio de Janeiro (RJ, n = 15), Rio Grande do Sul (RS, n = 10), Paraná (PR, n = 4), São Paulo (SP, n =3) and Minas Gerais (MG, n = 1). Our results showed that S. brasiliensis is highly prevalent among cats (96.9%) with sporotrichosis, while S. schenckii was identified only once. The genotype of Sporothrix from cats was found identical to S. brasiliensis from human sources confirming that the disease is transmitted by cats. Sporothrix brasiliensis presented low genetic diversity compared to its sister taxon S. schenckii. No evidence of recombination in S. brasiliensis was found by split decomposition or PHI-test analysis, suggesting that S. brasiliensis is a clonal species. Strains recovered in states SP, MG and PR share the genotype of the RJ outbreak, different from the RS clone. The occurrence of separate genotypes among strains indicated that the Brazilian S. brasiliensis epidemic has at least two distinct sources. We suggest that cats represent a major host and the main source of cat and human S. brasiliensis infections in Brazil.

  6. Early Gene Expression in Wounded Human Keratinocytes Revealed by DNA Microarray Analysis

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    Pascal Barbry

    2006-04-01

    Full Text Available Wound healing involves several steps: spreading of the cells, migration and proliferation. We have profiled gene expression during the early events of wound healing in normal human keratinocytes with a home-made DNA microarray containing about 1000 relevant human probes. An original wounding machine was used, that allows the wounding of up to 40% of the surface of a confluent monolayer of cultured cells grown on a Petri dish (compared with 5% with a classical ‘scratch’ method. The two aims of the present study were: (a to validate a limited number of genes by comparing the expression levels obtained with this technique with those found in the literature; (b to combine the use of the wounding machine with DNA microarray analysis for large-scale detection of the molecular events triggered during the early stages of the wound-healing process. The time-courses of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA and the signal transducer and transcription activator STAT3, were consistent with previously published data. This suggests that our methodologies are able to perform quantitative measurement of gene expression. Transcripts encoding two zinc finger proteins, ZFP36 and ZNF161, and the tumour necrosis factor α-induced protein TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen-activated protein kinase (p38MAPK in wound healing was shown after the inhibition of p38 by SB203580, but our results also suggest the existence of surrogate activating pathways.

  7. Age differences in the neural representation of working memory revealed by multi-voxel pattern analysis.

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    Joshua eCarp

    2010-11-01

    Full Text Available Working memory function declines across the lifespan. Computational models of aging attribute such memory impairments to reduced distinctiveness between neural representations of different mental states in old age, a phenomenon termed dedifferentiation. These models predict that neural distinctiveness should be reduced uniformly across experimental conditions in older adults. In contrast, the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH model predicts that the distinctiveness of neural representations should be increased in older adults (relative to young adults at low levels of task demand but reduced at high levels of demand. The present study used multi-voxel pattern analysis (MVPA to measure the effects of age and task demands on the distinctiveness of the neural representations of verbal and visuospatial working memory. Neural distinctiveness was estimated separately for memory encoding, maintenance, and retrieval, and for low, medium, and high memory loads. Results from sensory cortex during encoding and retrieval were consistent with the dedifferentiation hypothesis: distinctiveness of visual cortical representations during these phases was uniformly reduced in older adults, irrespective of memory load. However, maintenance-related responses in prefrontal and parietal regions yielded a strikingly different pattern of results. At low loads, older adults showed higher distinctiveness than younger adults; at high loads, this pattern reversed, such that distinctiveness was higher in young adults. This interaction between age group and memory load is at odds with the dedifferentiation hypothesis but consistent with CRUNCH. In sum, our results provide partial support for both dedifferentiation- and compensation-based models; we argue that comprehensive theories of cognitive aging must incorporate aspects of both models to fully explain complex patterns of age-related neuro-cognitive change.

  8. SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

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    Ahmed Idbaih

    Full Text Available Anaplastic oligodendrogliomas (AOD are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19(q10;p10, IDH1, IDH2, CIC and FUBP1 mutations.To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA," has been supported by the Institut National du Cancer (InCA. Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.

  9. Whole brain resting-state analysis reveals decreased functional connectivity in major depression

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    Ilya M. Veer

    2010-09-01

    Full Text Available Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within six months before inclusion and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxelwise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: 1 decreased bilateral amygdala and left anterior insula connectivity in an affective network, 2 reduced connectivity of the left frontal pole in a network associated with attention and working memory, and 3 decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or grey matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

  10. Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage of Drosophila FGFs

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    Stathopoulos Angelike

    2010-08-01

    Full Text Available Abstract Background As important regulators of developmental and adult processes in metazoans, Fibroblast Growth Factor (FGF proteins are potent signaling molecules whose activities must be tightly regulated. FGFs are known to play diverse roles in many processes, including mesoderm induction, branching morphogenesis, organ formation, wound healing and malignant transformation; yet much more remains to be learned about the mechanisms of regulation used to control FGF activity. Results In this work, we conducted an analysis of the functional domains of two Drosophila proteins, Thisbe (Ths and Pyramus (Pyr, which share homology with the FGF8 subfamily of ligands in vertebrates. Ths and Pyr proteins are secreted from Drosophila Schneider cells (S2 as smaller N-terminal fragments presumably as a result of intracellular proteolytic cleavage. Cleaved forms of Ths and Pyr can be detected in embryonic extracts as well. The FGF-domain is contained within the secreted ligand portion, and this domain alone is capable of functioning in the embryo when ectopically expressed. Through targeted ectopic expression experiments in which we assay the ability of full-length, truncated, and chimeric proteins to support cell differentiation, we find evidence that (1 the C-terminal domain of Pyr is retained inside the cell and does not seem to be required for receptor activation and (2 the C-terminal domain of Ths is secreted and, while also not required for receptor activation, this domain does plays a role in limiting the activity of Ths when present. Conclusions We propose that differential protein processing may account for the previously observed inequalities in signaling capabilities between Ths and Pyr. While the regulatory mechanisms are likely complex, studies such as ours conducted in a tractable model system may be able to provide insights into how ligand processing regulates growth factor activity.

  11. MtDNA analysis reveals enriched pathogenic mutations in Tibetan highlanders

    Science.gov (United States)

    Kang, Longli; Zheng, Hong-Xiang; Zhang, Menghan; Yan, Shi; Li, Lei; Liu, Lijun; Liu, Kai; Hu, Kang; Chen, Feng; Ma, Lifeng; Qin, Zhendong; Wang, Yi; Wang, Xiaofeng; Jin, Li

    2016-01-01

    Tibetan highlanders, including Tibetans, Monpas, Lhobas, Dengs and Sherpas, are considered highly adaptive to severe hypoxic environments. Mitochondrial DNA (mtDNA) might be important in hypoxia adaptation given its role in coding core subunits of oxidative phosphorylation. In this study, we employed 549 complete highlander mtDNA sequences (including 432 random samples) to obtain a comprehensive view of highlander mtDNA profile. In the phylogeny of a total of 36,914 sequences, we identified 21 major haplogroups representing founding events of highlanders, most of which were coalesced in 10 kya. Through founder analysis, we proposed a three-phase model of colonizing the plateau, i.e., pre-LGM Time (30 kya, 4.68%), post-LGM Paleolithic Time (16.8 kya, 29.31%) and Neolithic Time (after 8 kya, 66.01% in total). We observed that pathogenic mutations occurred far more frequently in 22 highlander-specific lineages (five lineages carrying two pathogenic mutations and six carrying one) than in the 6,857 haplogroups of all the 36,914 sequences (P = 4.87 × 10−8). Furthermore, the number of possible pathogenic mutations carried by highlanders (in average 3.18 ± 1.27) were significantly higher than that in controls (2.82 ± 1.40) (P = 1.89 × 10−4). Considering that function-altering and pathogenic mutations are enriched in highlanders, we therefore hypothesize that they may have played a role in hypoxia adaptation. PMID:27498855

  12. THREE-DIMENSIONAL RADIO AND X-RAY MODELING AND DATA ANALYSIS SOFTWARE: REVEALING FLARE COMPLEXITY

    Energy Technology Data Exchange (ETDEWEB)

    Nita, Gelu M.; Fleishman, Gregory D.; Gary, Dale E. [Center For Solar-Terrestrial Research, New Jersey Institute of Technology, Newark, NJ 07102 (United States); Kuznetsov, Alexey A. [Institute of Solar-Terrestrial Physics, Irkutsk 664033 (Russian Federation); Kontar, Eduard P. [School of Physics and Astronomy, The University of Glasgow, Glasgow G12 8QQ (United Kingdom)

    2015-02-01

    Many problems in solar physics require analysis of imaging data obtained in multiple wavelength domains with differing spatial resolution in a framework supplied by advanced three-dimensional (3D) physical models. To facilitate this goal, we have undertaken a major enhancement of our IDL-based simulation tools developed earlier for modeling microwave and X-ray emission. The enhanced software architecture allows the user to (1) import photospheric magnetic field maps and perform magnetic field extrapolations to generate 3D magnetic field models; (2) investigate the magnetic topology by interactively creating field lines and associated flux tubes; (3) populate the flux tubes with user-defined nonuniform thermal plasma and anisotropic, nonuniform, nonthermal electron distributions; (4) investigate the spatial and spectral properties of radio and X-ray emission calculated from the model; and (5) compare the model-derived images and spectra with observational data. The package integrates shared-object libraries containing fast gyrosynchrotron emission codes, IDL-based soft and hard X-ray codes, and potential and linear force-free field extrapolation routines. The package accepts user-defined radiation and magnetic field extrapolation plug-ins. We use this tool to analyze a relatively simple single-loop flare and use the model to constrain the magnetic 3D structure and spatial distribution of the fast electrons inside this loop. We iteratively compute multi-frequency microwave and multi-energy X-ray images from realistic magnetic flux tubes obtained from pre-flare extrapolations, and compare them with imaging data obtained by SDO, NoRH, and RHESSI. We use this event to illustrate the tool's use for the general interpretation of solar flares to address disparate problems in solar physics.

  13. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

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    Manuela Vanti

    2009-01-01

    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  14. Transcriptome analysis of a cnidarian – dinoflagellate mutualism reveals complex modulation of host gene expression

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    Phillips Wendy S

    2006-02-01

    Full Text Available Abstract Background Cnidarian – dinoflagellate intracellular symbioses are one of the most important mutualisms in the marine environment. They form the trophic and structural foundation of coral reef ecosystems, and have played a key role in the evolutionary radiation and biodiversity of cnidarian species. Despite the prevalence of these symbioses, we still know very little about the molecular modulators that initiate, regulate, and maintain the interaction between these two different biological entities. In this study, we conducted a comparative host anemone transcriptome analysis using a cDNA microarray platform to identify genes involved in cnidarian – algal symbiosis. Results We detected statistically significant differences in host gene expression profiles between sea anemones (Anthopleura elegantissima in a symbiotic and non-symbiotic state. The group of genes, whose expression is altered, is diverse, suggesting that the molecular regulation of the symbiosis is governed by changes in multiple cellular processes. In the context of cnidarian – dinoflagellate symbioses, we discuss pivotal host gene expression changes involved in lipid metabolism, cell adhesion, cell proliferation, apoptosis, and oxidative stress. Conclusion Our data do not support the existence of symbiosis-specific genes involved in controlling and regulating the symbiosis. Instead, it appears that the symbiosis is maintained by altering expression of existing genes involved in vital cellular processes. Specifically, the finding of key genes involved in cell cycle progression and apoptosis have led us to hypothesize that a suppression of apoptosis, together with a deregulation of the host cell cycle, create a platform that might be necessary for symbiont and/or symbiont-containing host cell survival. This first comprehensive molecular examination of the cnidarian – dinoflagellate associations provides critical insights into the maintenance and regulation of the

  15. Risk analysis reveals global hotspots for marine debris ingestion by sea turtles.

    Science.gov (United States)

    Schuyler, Qamar A; Wilcox, Chris; Townsend, Kathy A; Wedemeyer-Strombel, Kathryn R; Balazs, George; van Sebille, Erik; Hardesty, Britta Denise

    2016-02-01

    Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study and turtle species. There is no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris. PMID:26365568

  16. Transcriptome Analysis of Honeybee (Apis Mellifera) Haploid and Diploid Embryos Reveals Early Zygotic Transcription during Cleavage

    Science.gov (United States)

    Pires, Camilla Valente; Freitas, Flávia Cristina de Paula; Cristino, Alexandre S.; Dearden, Peter K.; Simões, Zilá Luz Paulino

    2016-01-01

    In honeybees, the haplodiploid sex determination system promotes a unique embryogenesis process wherein females develop from fertilized eggs and males develop from unfertilized eggs. However, the developmental strategies of honeybees during early embryogenesis are virtually unknown. Similar to most animals, the honeybee oocytes are supplied with proteins and regulatory elements that support early embryogenesis. As the embryo develops, the zygotic genome is activated and zygotic products gradually replace the preloaded maternal material. The analysis of small RNA and mRNA libraries of mature oocytes and embryos originated from fertilized and unfertilized eggs has allowed us to explore the gene expression dynamics in the first steps of development and during the maternal-to-zygotic transition (MZT). We localized a short sequence motif identified as TAGteam motif and hypothesized to play a similar role in honeybees as in fruit flies, which includes the timing of early zygotic expression (MZT), a function sustained by the presence of the zelda ortholog, which is the main regulator of genome activation. Predicted microRNA (miRNA)-target interactions indicated that there were specific regulators of haploid and diploid embryonic development and an overlap of maternal and zygotic gene expression during the early steps of embryogenesis. Although a number of functions are highly conserved during the early steps of honeybee embryogenesis, the results showed that zygotic genome activation occurs earlier in honeybees than in Drosophila based on the presence of three primary miRNAs (pri-miRNAs) (ame-mir-375, ame-mir-34 and ame-mir-263b) during the cleavage stage in haploid and diploid embryonic development. PMID:26751956

  17. Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis

    Directory of Open Access Journals (Sweden)

    Parker Albert

    2010-11-01

    Full Text Available Abstract Background Transcriptome analysis was applied to characterize the physiological activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared ranki ngs for a priori identified physiological marker genes between the biofilm and published data sets. Results Biofilms tolerated exposure to antibiotics, harbored steep oxygen concentration gradients, and exhibited stratified and heterogeneous spatial patterns of protein synthetic activity. Transcriptional profiling was performed and the signal intensity of each transcript was ranked to gain insight into the physiological state of the biofilm population. Similar rankings were obtained from data sets published in the GEO database http://www.ncbi.nlm.nih.gov/geo. By comparing the rank of genes selected as markers for particular physiological activities between the biofilm and comparator data sets, it was possible to infer qualitative features of the physiological state of the biofilm bacteria. These biofilms appeared, from their transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing slowly or exhibiting stationary phase character. Genes associated with elaboration of type IV pili were strongly expressed in the biofilm. The biofilm population did not indicate oxidative stress, homoserine lactone mediated quorum sensing, or activation of efflux pumps. Using correlations with transcript ranks, the average specific growth rate of biofilm cells was estimated to be 0.08 h-1. Conclusions Collectively these data underscore the oxygen-limited, slow-growing nature of the biofilm population and are consistent with antimicrobial tolerance due

  18. Large-scale mitochondrial DNA analysis of the domestic goat reveals six haplogroups with high diversity.

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    Saeid Naderi

    Full Text Available BACKGROUND: From the beginning of domestication, the transportation of domestic animals resulted in genetic and demographic processes that explain their present distribution and genetic structure. Thus studying the present genetic diversity helps to better understand the history of domestic species. METHODOLOGY/PRINCIPAL FINDINGS: The genetic diversity of domestic goats has been characterized with 2430 individuals from all over the old world, including 946 new individuals from regions poorly studied until now (mainly the Fertile Crescent. These individuals represented 1540 haplotypes for the HVI segment of the mitochondrial DNA (mtDNA control region. This large-scale study allowed the establishment of a clear nomenclature of the goat maternal haplogroups. Only five of the six previously defined groups of haplotypes were divergent enough to be considered as different haplogroups. Moreover a new mitochondrial group has been localized around the Fertile Crescent. All groups showed very high haplotype diversity. Most of this diversity was distributed among groups and within geographic regions. The weak geographic structure may result from the worldwide distribution of the dominant A haplogroup (more than 90% of the individuals. The large-scale distribution of other haplogroups (except one, may be related to human migration. The recent fragmentation of local goat populations into discrete breeds is not detectable with mitochondrial markers. The estimation of demographic parameters from mismatch analyses showed that all groups had a recent demographic expansion corresponding roughly to the period when domestication took place. But even with a large data set it remains difficult to give relative dates of expansion for different haplogroups because of large confidence intervals. CONCLUSIONS/SIGNIFICANCE: We propose standard criteria for the definition of the different haplogroups based on the result of mismatch analysis and on the use of sequences of

  19. Coxiella burnetii transcriptional analysis reveals serendipity clusters of regulation in intracellular bacteria.

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    Quentin Leroy

    Full Text Available Coxiella burnetii, the causative agent of the zoonotic disease Q fever, is mainly transmitted to humans through an aerosol route. A spore-like form allows C. burnetii to resist different environmental conditions. Because of this, analysis of the survival strategies used by this bacterium to adapt to new environmental conditions is critical for our understanding of C. burnetii pathogenicity. Here, we report the early transcriptional response of C. burnetii under temperature stresses. Our data show that C. burnetii exhibited minor changes in gene regulation under short exposure to heat or cold shock. While small differences were observed, C. burnetii seemed to respond similarly to cold and heat shock. The expression profiles obtained using microarrays produced in-house were confirmed by quantitative RT-PCR. Under temperature stresses, 190 genes were differentially expressed in at least one condition, with a fold change of up to 4. Globally, the differentially expressed genes in C. burnetii were associated with bacterial division, (pppGpp synthesis, wall and membrane biogenesis and, especially, lipopolysaccharide and peptidoglycan synthesis. These findings could be associated with growth arrest and witnessed transformation of the bacteria to a spore-like form. Unexpectedly, clusters of neighboring genes were differentially expressed. These clusters do not belong to operons or genetic networks; they have no evident associated functions and are not under the control of the same promoters. We also found undescribed but comparable clusters of regulation in previously reported transcriptomic analyses of intracellular bacteria, including Rickettsia sp. and Listeria monocytogenes. The transcriptomic patterns of C. burnetii observed under temperature stresses permits the recognition of unpredicted clusters of regulation for which the trigger mechanism remains unidentified but which may be the result of a new mechanism of epigenetic regulation.

  20. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation