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Sample records for putative functional markers

  1. ZDHHC8 as a candidate gene for schizophrenia: Analysis of a putative functional intronic marker in case-control and family-based association studies

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    Jabs Burkhard

    2005-10-01

    Full Text Available Abstract Background The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. Methods Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186. Results In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity χ2 = 4.43; p = 0.035. The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. Conclusion The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.

  2. Identification of putative candidate gene markers for grain zinc ...

    African Journals Online (AJOL)

    Gande

    2014-01-29

    Jan 29, 2014 ... with 96 rice genotypes showed three markers (OsZIP8a, OsNAC and OsZIP4b) with phenotypic variation of 11.0, 5.8 .... tent in wheat mapping population, ranging from 19.9 to .... Genotype×environment interaction for iron con-.

  3. Psychosocial dwarfism: psychopathological aspects and putative neuroendocrine markers.

    Science.gov (United States)

    Muñoz-Hoyos, Antonio; Molina-Carballo, Antonio; Augustin-Morales, Maríadelcarmen; Contreras-Chova, Francisco; Naranjo-Gómez, Ana; Justicia-Martínez, Fuensanta; Uberos, José

    2011-06-30

    There exists an extensive terminology for defining the situation of children who, in varying circumstances, suffer from affective deprivation (AD), within an unsatisfactory family situation or in institutions. Nevertheless, the neuroendocrine mechanisms (if they exist) determining it have yet to be identified. Our objective was to determine if specific neuroendocrine markers, all of them previously implicated in affective disorders, could be modified, and in which sense, in affective deprivation syndrome of the child. For this purpose, we studied three separate groups of children: (1) control group (CG); (2) children suffering from AD; and (3) children with non-organic failure to thrive (NOFT). In every case, we studied the serum levels of melatonin, serotonin, β-endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway tryptophan metabolites (both during the day and at night). Significantly, there was a conspicuous reduction in the levels of each of the neuroendocrine markers (melatonin, serotonin, β-endorphins and ACTH) in the group suffering from affective deficiency, a diminution which was even more noticeable in the group of patients presenting delayed growth. Furthermore, as also occurs in other affective disorders, there were corresponding modifications in the metabolisation of tryptophan. We report the existence of neuroendocrine mechanisms that are associated with the above-mentioned clinical manifestations in these patients, mechanisms that may underlie the close connection existing between AD syndrome and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise a single process, but one with a different evolutionary continuum of psychosocial dwarfism. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Markers of renal function tests

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    Shivaraj Gowda

    2010-04-01

    Full Text Available Background: The markers of renal function test assess the normal functioning of kidneys. These markers may be radioactive and non radioactive. They indicate the glomerular filtration rate, concentrating and diluting capacity of kidneys (tubular function. If there is an increase or decrease in the valves of these markers it indicates dysfunction of kidney. Aim: The aim of this review is to compare and analyze the present and newer markers of renal function tests which help in diagnosis of clinical disorders. Material & Methods: An extensive literature survey was done aiming to compare and compile renal function tests makers required in diagnosis of diseases. Results: Creatinine, urea, uric acid and electrolytes are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin C and β-Trace Protein. Conclusion: We conclude that further investigation is necessary to define these biomarkers in terms of usefulness in assessing renal function.

  5. Expression of putative markers of pluripotency in equine embryonic and adult tissues.

    Science.gov (United States)

    Esteves, Cristina L; Sharma, Ruchi; Dawson, Lucy; Taylor, Sarah E; Pearson, Gemma; Keen, John A; McDonald, Kieran; Aurich, Christine; Donadeu, F Xavier

    2014-12-01

    Expression of several putative markers of pluripotency (OCT4, SOX2, NANOG, LIN28A, REX1, DNMT3B and TERT) was examined in a range of equine tissues, including early embryos, induced pluripotent stem cells (iPSCs), testis, adipose- and bone marrow-derived mesenchymal stromal cells (MSCs), and keratinocytes. Transcript levels of all markers were highest in embryos and iPSCs and, except for SOX2, were very low or undetectable in keratinocytes. Mean expression levels of all markers were lower in testis than in embryos or iPSCs and, except for DNMT3B, were higher in testis than in MSCs. Expression of OCT4, NANOG and DNMT3B, but not the other markers, was detected in MSCs. Of all markers analysed, only LIN28A, REX1 and TERT were associated exclusively with pluripotent cells in the horse. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Identification of Putative Molecular Markers Associated with Root Traits in Coffea canephora Pierre ex Froehner

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    Devaraja Achar

    2015-01-01

    Full Text Available Coffea canephora exhibit poor root system and are very sensitive to drought stress that affects growth and production. Deeper root system has been largely empirical as better avoidance to soil water limitation in drought condition. The present study aimed to identify molecular markers linked to high root types in Coffea canephora using molecular markers. Contrasting parents, L1 valley with low root and S.3334 with high root type, were crossed, and 134 F1 individuals were phenotyped for root and associated physiological traits (29 traits and genotyped with 41 of the 320 RAPD and 9 of the 55 SSR polymorphic primers. Single marker analysis was deployed for detecting the association of markers linked to root associated traits by SAS software. There were 13 putative RAPD markers associated with root traits such as root length, secondary roots, root dry weight, and root to shoot ratio, in which root length associated marker OPS1850 showed high phenotypic variance of 6.86%. Two microsatellite markers linked to root length (CPCM13400 and root to shoot ratio (CM211300. Besides, 25 markers were associated with more than one trait and few of the markers were associated with positively related physiological traits and can be used in marker assisted trait selection.

  7. A putative resistant DNA marker for wool yellowing susceptibility in sheep

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    Benavides M.V.

    2000-01-01

    Full Text Available An Australian Merino flock was screened for low (resistant and high (susceptible yellow predictive colour (YPC breeding values in order to compare extreme individuals using the differential display of mRNA technique. One differentially expressed cDNA band was visualised only in the resistant group. This band showed no identity with the DNA sequences of public databases; however, they showed short homologies with three database sequences related to transmembrane signalling functions. The use of these candidate genes as DNA markers needs to be confirmed against sheep with a wide range of susceptibility to wool yellowing to verify the results.

  8. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

    Science.gov (United States)

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  9. Transcriptional coactivator undifferentiated embryonic cell transcription factor 1 expressed in spermatogonial stem cells: a putative marker of boar spermatogonia.

    Science.gov (United States)

    Lee, Won-Young; Lee, Kyung-Hoon; Heo, Young-Tae; Kim, Nam-Hyung; Kim, Jin-Hoi; Kim, Jae-Hwan; Moon, Sung-Hwan; Chung, Hak-Jae; Yoon, Min-Jung; Song, Hyuk

    2014-11-30

    Spermatogenesis is initiated from spermatogonial stem cells (SSCs), which are derived from gonocytes. Although some rodent SSC markers have been investigated, other species- and developmental stage-specific markers of spermatogonia have not been identified. The objective of this study was to characterize the expression of undifferentiated embryonic cell transcription factor 1 (UTF1) gene as a potential marker for spermatogonia and SSCs in the boar testis. In boar testis tissue at pre-pubertal stages (tissues collected at 5, 30, and 60 days of age), UTF1 gene expression was detected in almost all spermatogonia cells that expressed a protein gene product 9.5 (PGP9.5), and immunocytochemical analysis of isolated total testicular cells showed that 91.14% of cells staining for PGP9.5 also stained for UTF1. However, in boar testis tissue at pubertal and post-pubertal stages (tissues collected at 90, 120, 150, and 180 days of age), UTF1 was not detected in all PGP9.5-positive cells in the basement membrane. While some PGP9.5-positive cells stained for UTF1, other cells stained only for PGP9.5 or UTF1. PGP9.5, UTF1, and NANOG was assessed in in vitro cultures of pig SSCs (pSSCs) from testes collected at 5 days of age. The relative amounts of PGP9.5, NANOG, and UTF1 mRNA were greater in pSSC colonies than in testis and muscle tissue. Thus, the UTF1 gene is expressed in PGP9.5-positive spermatogonia cells of pigs at 5 days of age, and its expression is maintained in cultured pSSC colonies, suggesting that UTF1 is a putative marker for early-stage spermatogonia in the pre-pubertal pig testis. These findings will facilitate the study of spermatogenesis and applications in germ cell research.

  10. Brcal: A Review of Structure and Putative Functions

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    James W.E. Paterson

    1998-01-01

    Full Text Available BRCA1 is a complex gene implicated in familial breast and ovarian cancer. Although it is almost certainly a tumour suppressor, it is also essential for the normal growth and development of embryonic cells. BRCA1 is probably involved in DNA damage and repair, in cell cycle regulation, and in differentiation of celis. It remains to be established whether all these functions are subserved by single mechanism or pathway. Since the cloning of BRCA1 in 1994, much has been learned about the function of the gene. However, a great deal more still has to be uncovered. The size of the protein coded by the BRCA1 gene and the variety of transcripts argues for a complexity of function and regulation that will provide intellectual and technical challenges for years to come.

  11. Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

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    M.L. Costa

    2004-12-01

    Full Text Available Desmin is the intermediate filament (IF protein occurring exclusively in muscle and endothelial cells. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique to muscle. Desmin was purified in 1977, the desmin gene was characterized in 1989, and knock-out animals were generated in 1996. Several isoforms have been described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle cells, but can be more concentrated in some particular structures, such as dense bodies, around the nuclei, around the Z-line or in costameres. Desmin is up-regulated in muscle-derived cellular adaptations, including conductive fibers in the heart, electric organs, some myopathies, and experimental treatments with drugs that induce muscle degeneration, like phorbol esters. Many molecules have been reported to associate with desmin, such as other IF proteins (including members of the membrane dystroglycan complex, nebulin, the actin and tubulin binding protein plectin, the molecular motor dynein, the gene regulatory protein MyoD, DNA, the chaperone alphaB-crystallin, and proteases such as calpain and caspase. Desmin has an important medical role, since it is used as a marker of tumors' origin. More recently, several myopathies have been described, with accumulation of desmin deposits. Yet, after almost 30 years since its identification, the function of desmin is still unclear. Suggested functions include myofibrillogenesis, mechanical support for the muscle, mitochondrial localization, gene expression regulation, and intracellular signaling. This review focuses on the biochemical interactions of desmin, with a discussion of its putative functions.

  12. EpCAM is a putative stem marker in retinoblastoma and an effective target for T-cell-mediated immunotherapy

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    Mitra, Moutushy; Kandalam, Mallikarjuna; Harilal, Anju; Verma, Rama Shenkar; Krishnan, Uma Maheswari; Swaminathan, Sethuraman

    2012-01-01

    Purpose The molecular markers cluster of differentiation (CD)24, CD44, adenosine tri-phosphate (ATP) binding cassette protein G2 (ABCG2), and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of cancer stem cells. In this study we characterized the EpCAM+ retinoblastoma (RB) cells for their cancer stem-like properties in vitro. Additionally, we targeted RB tumor cells via redirecting T cells using bispecific EpCAM×CD3 antibody. Methods Flow cytometry was used to study the co-expression of EpCAM with putative cancer stem cell markers, such as CD44, CD24, and ABCG2, in RB primary tumors. In vitro methyl thiazol tetrazolium (MTT) assay, invasion assay, and neurosphere formation assay were performed to characterize EpCAM+ cells for their cancer stem/progenitor cell-like properties. We assessed the in vitro efficacy of bispecific EpCAM×CD3 antibody on RB tumor cell proliferation and validated the results by evaluating effector cytokine production in the culture medium with the ELISA method. Results EpCAM was co-expressed with all cancer stem cell markers (CD44, CD24, and ABCG2) in primary RB tumors. EpCAM+ cells showed significantly higher proliferative invasive potential and neurosphere formation in vitro compared to EpCAM– Y79 cells. EpCAM+ cells showed higher β-catenin expression compared to EpCAMˉ cells. EpCAM×CD3 significantly retarded proliferation of RB primary tumor cells. EpCAM×CD3 effectively induced the secretion of effector cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-2, and transforming growth factor (TGF)-β1, and also perforin levels by pre-activated lymphocytes. Conclusions EpCAM might be a novel cancer stem cell marker in RB. EpCAM×CD3 antibody redirecting T cells to attack RB tumor cells may prove effective in RB management. Further preclinical studies are needed to confirm the initial findings of our study. PMID:22328825

  13. Structure and functional annotation of hypothetical proteins having putative Rubisco activase function from Vitis vinifera.

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    Kumar, Suresh

    2015-01-01

    Rubisco is a very large, complex and one of the most abundant proteins in the world and comprises up to 50% of all soluble protein in plants. The activity of Rubisco, the enzyme that catalyzes CO2 assimilation in photosynthesis, is regulated by Rubisco activase (Rca). In the present study, we searched for hypothetical protein of Vitis vinifera which has putative Rubisco activase function. The Arabidopsis and tobacco Rubisco activase protein sequences were used as seed sequences to search against Vitis vinifera in UniprotKB database. The selected hypothetical proteins of Vitis vinifera were subjected to sequence, structural and functional annotation. Subcellular localization predictions suggested it to be cytoplasmic protein. Homology modelling was used to define the three-dimensional (3D) structure of selected hypothetical proteins of Vitis vinifera. Template search revealed that all the hypothetical proteins share more than 80% sequence identity with structure of green-type Rubisco activase from tobacco, indicating proteins are evolutionary conserved. The homology modelling was generated using SWISS-MODEL. Several quality assessment and validation parameters computed indicated that homology models are reliable. Further, functional annotation through PFAM, CATH, SUPERFAMILY, CDART suggested that selected hypothetical proteins of Vitis vinifera contain ATPase family associated with various cellular activities (AAA) and belong to the AAA+ super family of ring-shaped P-loop containing nucleoside triphosphate hydrolases. This study will lead to research in the optimization of the functionality of Rubisco which has large implication in the improvement of plant productivity and resource use efficiency.

  14. Proteomic Profiling of the Microsomal Root Fraction: Discrimination of Pisum sativum L. Cultivars and Identification of Putative Root Growth Markers

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    Meisrimler, Claudia-Nicole; Wienkoop, Stefanie; Lüthje, Sabine

    2017-01-01

    Legumes are a large and economically important family, containing a variety of crop plants. Alongside different cereals, some fruits, and tropical roots, a number of leguminosae evolved for millennia as crops with human society. One of these legumes is Pisum sativum L., the common garden pea. In the past, breeding has been largely selective on improved above-ground organs. However, parameters, such as root-growth, which determines acquisition of nutrients and water, have largely been underestimated. Although the genome of P. sativum is still not fully sequenced, multiple proteomic studies have been published on a variety of physiological aspects in the last years. The presented work focused on the connection between root length and the influence of the microsomal root proteome of four different pea cultivars after five days of germination (cultivar Vroege, Girl from the Rhineland, Kelvedon Wonder, and Blauwschokker). In total, 60 proteins were identified to have significantly differential abundances in the four cultivars. Root growth of five-days old seedlings and their microsomal proteome revealed a similar separation pattern, suggesting that cultivar-specific root growth performance is explained by differential membrane and ribosomal protein levels. Hence, we reveal and discuss several putative root growth protein markers possibly playing a key role for improved primary root growth breeding strategies. PMID:28257117

  15. Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

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    Luo Hongmei

    2011-12-01

    -generation sequencing (NGS technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for P. notoginseng. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.

  16. Transcriptome analysis of Panax vietnamensis var. fuscidicus discovers putative ocotillol-type ginsenosides biosynthesis genes and genetic markers.

    Science.gov (United States)

    Zhang, Guang-Hui; Ma, Chun-Hua; Zhang, Jia-Jin; Chen, Jun-Wen; Tang, Qing-Yan; He, Mu-Han; Xu, Xiang-Zeng; Jiang, Ni-Hao; Yang, Sheng-Chao

    2015-03-08

    liquid chromatography (HPLC) and evaporative light scattering detector (ELSD). The genomic resources generated from P. vietnamensis var. fuscidiscus provide new insights into the identification of putative genes involved in triterpenoid saponins biosynthesis pathway. This will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level. The SSR markers identified and developed in this study show genetic diversity for this important crop and will contribute to marker-assisted breeding for P. vietnamensis var. fuscidiscus.

  17. Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

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    Watanabe Hiromitsu

    2010-06-01

    Full Text Available Abstract Background Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1 is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions. Methods An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia. Results DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2/spasmolytic polypeptide-expressing metaplasia (SPEM emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM. Conclusion The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic

  18. A putative flavin-containing mono-oxygenase as a marker for certain defense and cell death pathways

    DEFF Research Database (Denmark)

    Olszak, Brian; Malinovsky, Frederikke Gro; Brodersen, Peter

    2006-01-01

    mRNA of the putative Arabidopsis flavin mono-oxygenase encoded by At1g19250 (here designated AtFMO GenBank accession no. NM_101783 ) accumulated to high levels in the acd11 and lsd1 mutants that exhibit run-away cell death, but not in mutants with constitutive defense responses. AtFMO mRNA accumu......mRNA of the putative Arabidopsis flavin mono-oxygenase encoded by At1g19250 (here designated AtFMO GenBank accession no. NM_101783 ) accumulated to high levels in the acd11 and lsd1 mutants that exhibit run-away cell death, but not in mutants with constitutive defense responses. AtFMO m...

  19. Expression of SOCS1 and the downstream targets of its putative tumor suppressor functions in prostate cancer.

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    Chevrier, Martin; Bobbala, Diwakar; Villalobos-Hernandez, Alberto; Khan, Md Gulam Musawwir; Ramanathan, Sheela; Saucier, Caroline; Ferbeyre, Gerardo; Geha, Sameh; Ilangumaran, Subburaj

    2017-02-24

    Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21(CIP1) (p21). Here, we studied the expression of SOCS1 and the downstream targets of its putative tumor suppressor functions (p53, MET and p21) in human PCa specimens to evaluate their significance as markers of disease prognosis. Tissue microarrays were constructed of 78 archived prostatectomy specimens that were grouped according to the recommendations of the International Society of Urological Pathology (ISUP) based on the Gleason patterns. SOCS1, p53, MET and p21 protein expression were evaluated by immunohistochemical staining alongside the common prostate cancer-related markers Ki67, prostein and androgen receptor. Statistical correlations between the staining intensities of these markers and ISUP grade groups, local invasion or lymph node metastasis were evaluated. SOCS1 showed diffuse staining in the prostatic epithelium. SOCS1 staining intensity correlated inversely with the ISUP grade groups (ρ = -0.4687, p <0.0001) and Ki67 (ρ = -0.2444, p = 0.031), and positively with prostein (ρ = 0.3511, p = 0.0016). Changes in SOCS1 levels did not significantly associate with those of p53, MET or p21. However, p21 positively correlated with androgen receptor expression (ρ = -0.1388, p = 0.0003). A subset of patients with regional lymph node metastasis, although small in number, showed reduced SOCS1 expression and increased expression of

  20. Putative resistance gene markers associated with quantitative trait loci for fire blight resistance in Malus ‘Robusta 5’ accessions

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    Gardiner Susan E

    2012-04-01

    Full Text Available Abstract Background Breeding of fire blight resistant scions and rootstocks is a goal of several international apple breeding programs, as options are limited for management of this destructive disease caused by the bacterial pathogen Erwinia amylovora. A broad, large-effect quantitative trait locus (QTL for fire blight resistance has been reported on linkage group 3 of Malus ‘Robusta 5’. In this study we identified markers derived from putative fire blight resistance genes associated with the QTL by integrating further genetic mapping studies with bioinformatics analysis of transcript profiling data and genome sequence databases. Results When several defined E.amylovora strains were used to inoculate three progenies from international breeding programs, all with ‘Robusta 5’ as a common parent, two distinct QTLs were detected on linkage group 3, where only one had previously been mapped. In the New Zealand ‘Malling 9’ X ‘Robusta 5’ population inoculated with E. amylovora ICMP11176, the proximal QTL co-located with SNP markers derived from a leucine-rich repeat, receptor-like protein ( MxdRLP1 and a closely linked class 3 peroxidase gene. While the QTL detected in the German ‘Idared’ X ‘Robusta 5’ population inoculated with E. amylovora strains Ea222_JKI or ICMP11176 was approximately 6 cM distal to this, directly below a SNP marker derived from a heat shock 90 family protein gene ( HSP90. In the US ‘Otawa3’ X ‘Robusta5’ population inoculated with E. amylovora strains Ea273 or E2002a, the position of the LOD score peak on linkage group 3 was dependent upon the pathogen strains used for inoculation. One of the five MxdRLP1 alleles identified in fire blight resistant and susceptible cultivars was genetically associated with resistance and used to develop a high resolution melting PCR marker. A resistance QTL detected on linkage group 7 of the US population co-located with another HSP90 gene-family member and a WRKY

  1. The Function of Discourse Markers in Arabic Newspaper Opinion Articles

    Science.gov (United States)

    Al Kohlani, Fatima A.

    2010-01-01

    The present study examines the function of discourse markers in Arabic newspaper opinion articles. In this study, discourse markers are not only connecting- words that contribute to the cohesion of text, but they are also crucial tools for achieving communicative act in the text. These expressions that come from different grammatical classes and…

  2. liver function markers and associated serum electrolytes changes in ...

    African Journals Online (AJOL)

    2013-09-09

    Sep 9, 2013 ... Results: Serum liver function markers were significantly altered in HIV infected individuals compared ... correlated with protein levels (r = 0.917) and vice versa. .... hypertension, diabetes or alcohol abuse or history of jaundice ...

  3. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

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    Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Smith, G D; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

    2016-08-01

    Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

  4. Characterization of a new Vaccinia virus isolate reveals the C23L gene as a putative genetic marker for autochthonous Group 1 Brazilian Vaccinia virus.

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    Felipe L Assis

    Full Text Available Since 1999, several Vaccinia virus (VACV isolates, the etiological agents of bovine vaccinia (BV, have been frequently isolated and characterized with various biological and molecular methods. The results from these approaches have grouped these VACV isolates into two different clusters. This dichotomy has elicited debates surrounding the origin of the Brazilian VACV and its epidemiological significance. To ascertain vital information to settle these debates, we and other research groups have made efforts to identify molecular markers to discriminate VACV from other viruses of the genus Orthopoxvirus (OPV and other VACV-BR groups. In this way, some genes have been identified as useful markers to discriminate between the VACV-BR groups. However, new markers are needed to infer ancestry and to correlate each sample or group with its unique epidemiological and biological features. The aims of this work were to characterize a new VACV isolate (VACV DMTV-2005 molecularly and biologically using conserved and non-conserved gene analyses for phylogenetic inference and to search for new genes that would elucidate the VACV-BR dichotomy. The VACV DMTV-2005 isolate reported in this study is biologically and phylogenetically clustered with other strains of Group 1 VACV-BR, the most prevalent VACV group that was isolated during the bovine vaccinia outbreaks in Brazil. Sequence analysis of C23L, the gene that encodes for the CC-chemokine-binding protein, revealed a ten-nucleotide deletion, which is a new Group 1 Brazilian VACV genetic marker. This deletion in the C23L open reading frame produces a premature stop-codon that is shared by all Group 1 VACV-BR strains and may also reflect the VACV-BR dichotomy; the deletion can also be considered to be a putative genetic marker for non-virulent Brazilian VACV isolates and may be used for the detection and molecular characterization of new isolates.

  5. Epigenetic Markers of Renal Function in African Americans

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    Samantha M. Bomotti

    2013-01-01

    Full Text Available Chronic kidney disease (CKD is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA study. We then evaluated (1 whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR, (2 whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3 how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30 appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans.

  6. In silico mining of putative microsatellite markers from whole genome sequence of water buffalo (Bubalus bubalis and development of first BuffSatDB

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    Sarika

    2013-01-01

    Full Text Available Abstract Background Though India has sequenced water buffalo genome but its draft assembly is based on cattle genome BTau 4.0, thus de novo chromosome wise assembly is a major pending issue for global community. The existing radiation hybrid of buffalo and these reported STR can be used further in final gap plugging and “finishing” expected in de novo genome assembly. QTL and gene mapping needs mining of putative STR from buffalo genome at equal interval on each and every chromosome. Such markers have potential role in improvement of desirable characteristics, such as high milk yields, resistance to diseases, high growth rate. The STR mining from whole genome and development of user friendly database is yet to be done to reap the benefit of whole genome sequence. Description By in silico microsatellite mining of whole genome, we have developed first STR database of water buffalo, BuffSatDb (Buffalo MicroSatellite Database (http://cabindb.iasri.res.in/buffsatdb/ which is a web based relational database of 910529 microsatellite markers, developed using PHP and MySQL database. Microsatellite markers have been generated using MIcroSAtellite tool. It is simple and systematic web based search for customised retrieval of chromosome wise and genome-wide microsatellites. Search has been enabled based on chromosomes, motif type (mono-hexa, repeat motif and repeat kind (simple and composite. The search may be customised by limiting location of STR on chromosome as well as number of markers in that range. This is a novel approach and not been implemented in any of the existing marker database. This database has been further appended with Primer3 for primer designing of the selected markers enabling researcher to select markers of choice at desired interval over the chromosome. The unique add-on of degenerate bases further helps in resolving presence of degenerate bases in current buffalo assembly. Conclusion Being first buffalo STR database in the world

  7. High-resolution array comparative genomic hybridization of chromosome 8q: evaluation of putative progression markers for gastroesophageal junction adenocarcinomas.

    Science.gov (United States)

    van Duin, M; van Marion, R; Vissers, K J; Hop, W C J; Dinjens, W N M; Tilanus, H W; Siersema, P D; van Dekken, H

    2007-01-01

    Amplification of 8q is frequently found in gastroesophageal junction (GEJ) cancer. It is usually detected in high-grade, high-stage GEJ adenocarcinomas. Moreover, it has been implicated in tumor progression in other cancer types. In this study, a detailed genomic analysis of 8q was performed on a series of GEJ adenocarcinomas, including 22 primary adenocarcinomas, 13 cell lines and two xenografts, by array comparative genomic hybridization (aCGH) with a whole chromosome 8q contig array. Of the 37 specimens, 21 originated from the esophagus and 16 were derived from the gastric cardia. Commonly overrepresented regions were identified at distal 8q, i.e. 124-125 Mb (8q24.13), at 127-128 Mb (8q24.21), and at 141-142 Mb (8q24.3). From these regions six genes were selected with putative relevance to cancer: ANXA13, MTSS1, FAM84B (alias NSE2), MYC, C8orf17 (alias MOST-1) and PTK2 (alias FAK). In addition, the gene EXT1 was selected since it was found in a specific amplification in cell line SK-GT-5. Quantitative RT-PCR analysis of these seven genes was subsequently performed on a panel of 24 gastroesophageal samples, including 13 cell lines, two xenografts and nine normal stomach controls. Significant overexpression was found for MYC and EXT1 in GEJ adenocarcinoma cell lines and xenografts compared to normal controls. Expression of the genes MTSS1, FAM84B and C8orf17 was found to be significantly decreased in this set of cell lines and xenografts. We conclude that, firstly, there are other genes than MYC involved in the 8q amplification in GEJ cancer. Secondly, the differential expression of these genes contributes to unravel the biology of GEJ adenocarcinomas.

  8. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

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    Piotr Bednarczyk

    Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

  9. Multiple functions of mfa-1, a putative pheromone precursor gene of Neurospora crassa.

    Science.gov (United States)

    Kim, Hyojeong; Metzenberg, Robert L; Nelson, Mary Anne

    2002-12-01

    A putative pheromone precursor gene of Neurospora crassa, mfa-1 (which encodes mating factor a-1), was identified as the most abundant clone in starved mycelial and perithecial cDNA libraries. Northern analysis demonstrated high mfa-1 expression in all mating type a tissues and suggested low expression levels in mat A tissues. The mfa-1 gene was expressed as an approximately 1.2-kb transcript predicted to encode a 24-residue peptide, followed by a long 3' untranslated region (3' UTR). The predicted MFA1 sequence showed 100% sequence identity to PPG2 of Sordaria macrospora and structural similarity (a carboxy-terminal CAAX motif) to many hydrophobic fungal pheromone precursors. Mutants with a disrupted open reading frame (ORF) in which the critical cysteine residue had been changed to a nonprenylatable residue, tyrosine (YAAX mutants), were isolated, as were mfa-1 mutants with intact ORFs but multiple mutations in the 3' noncoding region (CAAX mutants). The 3' UTR is required for the full range of mfa-1 gene activity. Both classes of mutants showed delayed and reduced vegetative growth (which was suppressed by supplementation with a minute amount [30 micro M] of ornithine, citrulline, or arginine), as well as aberrant sexual development. When crossed as female parents to wild-type males, the CAAX and YAAX mutants showed greatly reduced ascospore production. No ascospores were produced in homozygous mfa-1 crosses. As males, YAAX mat a mutants were unable to attract wild-type mat A trichogynes (female-specific hyphae) or to initiate sexual development, while CAAX mat a mutants were able to mate and produce sexual progeny despite their inability to attract mat A trichogynes. In the mat A background, both CAAX and YAAX mutants showed normal male fertility but defective vegetative growth and aberrant female sexual development. Thus, the mfa-1 gene appears to have multiple roles in N. crassa development: (i) it encodes a hydrophobic pheromone with a putative farnesylated

  10. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

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    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  11. The evolution and putative function of phosducin-like proteins in the malaria parasite Plasmodium.

    Science.gov (United States)

    Putonti, Catherine; Quach, Bryan; Kooistra, Rachel L; Kanzok, Stefan M

    2013-01-01

    Ubiquitous to the proteomes of all living species is the presence of proteins containing the thioredoxin (Trx)-domain. The best characterized Trx-domain containing proteins include the enzymes involved in cellular redox metabolism facilitated by their cysteine-containing active site. But not all members of the Trx-fold superfamily exhibit this catalytic motif, e.g., the phosducin-like (PhLP) family of proteins. Genome sequencing efforts have uncovered new Trx-domain containing proteins, and their redox activity and cellular functions have yet to be determined. The genome of the malaria parasite Plasmodium contains multiple thioredoxins and thioredoxin-like proteins which are of considerable interest given their role in the parasite's antioxidant defense. While adaptations within the Trx-domain have been studied, primarily with respect to redox active structures, PhLP proteins have not been examined. Using the uncharacterized phosducin-like protein from Plasmodium berghei PhLP-1, we investigated the evolution of PhLP proteins across all branches of the tree of life. As a result of our analysis, we have discovered the presence of two additional PhLP proteins in Plasmodium, PhLP-2 and PhLP-3. Sequence homology with annotated PhLP proteins in other species confirms that the Plasmodium PhLP-2 and PhLP-3 belong to the PhLP family of proteins. Furthermore, as a result of our analysis we hypothesize that the PhLP-2 thioredoxin was lost over time given its absence from higher-order eukaryotes. Probing deeper into the putative function of these proteins, inspection of the active sites indicate that PbPhLP-1 and PbPhLP-2 may be redox active while PbPhLP-3 is very likely not. The results of this phylogenetic study provide insight into the emergence of this family of Trx-domain containing proteins.

  12. Functional Characterization of Four Putative δ1-Pyrroline-5-Carboxylate Reductases from Bacillus subtilis

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    Giuseppe Forlani

    2017-08-01

    Full Text Available In most living organisms, the amino acid proline is synthesized starting from both glutamate and ornithine. In prokaryotes, in the absence of an ornithine cyclodeaminase that has been identified to date only in a small number of soil and plant bacteria, these pathways share the last step, the reduction of δ1-pyrroline-5-carboxylate (P5C catalyzed by P5C reductase (EC 1.5.1.2. In several species, multiple forms of P5C reductase have been reported, possibly reflecting the dual function of proline. Aside from its common role as a building block of proteins, proline is indeed also involved in the cellular response to osmotic and oxidative stress conditions. Genome analysis of Bacillus subtilis identifies the presence of four genes (ProH, ProI, ProG, and ComER that, based on bioinformatic and phylogenic studies, were defined as respectively coding a putative P5C reductase. Here we describe the cloning, heterologous expression, functional analysis and small-angle X-ray scattering studies of the four affinity-purified proteins. Results showed that two of them, namely ProI and ComER, lost their catalytic efficiency or underwent subfunctionalization. In the case of ComER, this could be likely explained by the loss of the ability to form a dimer, which has been previously shown to be an essential structural feature of the catalytically active P5C reductase. The properties of the two active enzymes are consistent with a constitutive role for ProG, and suggest that ProH expression may be beneficial to satisfy an increased need for proline.

  13. Functional Characterization of Four Putative d1-Pyrroline-5-Carboxylate Reductases from Bacillus subtilis

    Energy Technology Data Exchange (ETDEWEB)

    Forlani, Giuseppe; Nocek, Boguslaw; Chakravarthy, Srinivas; Joachimiak, Andrzej

    2017-08-02

    In most living organisms, the amino acid proline is synthesized starting from both glutamate and ornithine. In prokaryotes, in the absence of an ornithine cyclodeaminase that has been identified to date only in a small number of soil and plant bacteria, these pathways share the last step, the reduction of delta(1)-pyrroline-5-carboxylate (P5C) catalyzed by P5C reductase (EC 1.5.1.2). In several species, multiple forms of P5C reductase have been reported, possibly reflecting the dual function of proline. Aside from its common role as a building block of proteins, proline is indeed also involved in the cellular response to osmotic and oxidative stress conditions. Genome analysis of Bacillus subtilis identifies the presence of four genes (ProH, ProI, ProG, and ComER) that, based on bioinformatic and phylogenic studies, were defined as respectively coding a putative P5C reductase. Here we describe the cloning, heterologous expression, functional analysis and small-angle X-ray scattering studies of the four affinity-purified proteins. Results showed that two of them, namely ProI and ComER, lost their catalytic efficiency or underwent subfunctionalization. In the case of ComER, this could be likely explained by the loss of the ability to form a dimer, which has been previously shown to be an essential structural feature of the catalytically active P5C reductase. The properties of the two active enzymes are consistent with a constitutive role for ProG, and suggest that ProH expression may be beneficial to satisfy an increased need for proline.

  14. Epidermal growth factor receptor in the prawn Macrobrachium rosenbergii: function and putative signaling cascade.

    Science.gov (United States)

    Sharabi, Omri; Ventura, Tomer; Manor, Rivka; Aflalo, Eliahu D; Sagi, Amir

    2013-09-01

    Epidermal growth factor receptors (EGFRs) are highly conserved members of the tyrosine kinase receptor superfamily found in metazoans and plants. In arthropods, EGFRs are vital for the proper development of embryos and of adult limbs, gonads, and eyes as well as affecting body size. In searching for genes involved in the growth and development of our model organism, the decapod crustacean (Macrobrachium rosenbergii), a comprehensive transcript library was established using next-generation sequencing. Using this library, the expression of several genes assigned to the signal transduction pathways mediated by EGFRs was observed, including a transcript encoding M. rosenbergii EGFR (Mr-EGFR), several potential ligands upstream to the receptor, and most of the putative downstream signal transducer genes. The deduced protein encoded by Mr-EGFR, representing the first such receptor reported thus far in crustaceans, shows sequence similarity to other arthropod EGFRs. The M. rosenbergii gene is expressed in most tested tissues. The role of Mr-EGFR was revealed by temporarily silencing the transcript through weekly injections of double-stranded Mr-EGFR RNA. Such treatment resulted in a significant reduction in growth and a delay in the appearance of a male secondary sexual characteristic, namely the appendix masculina. An additional function of Mr-EGFR was revealed with respect to eye development. Although the optic ganglion appeared to have retained its normal morphology, Mr-EGFR-silenced individuals developed abnormal eyes that presented irregular organization of the ommatidia, reflected by unorganized receptor cells occupying large areas of the dioptric portion and by a shortened crystalline tract layer.

  15. The immune function of MHC class II molecules mutated in the putative superdimer interface.

    Science.gov (United States)

    Hayball, John D; Lake, Richard A

    2005-05-01

    Analysis of the crystal structure of human class II (HLA-DR1) molecules suggests that the alphabeta heterodimer may be further ordered as a dimer of heterodimers (superdimer), leading to the hypothesis that T cell receptor dimerisation is a mechanism for initiating signaling events preceding T cell activation. The interface between pairs of molecules is stabilised by both salt bridges, polar and hydrophobic interactions. The residues that form the superdimer interface occur in three areas distinct from the antigen-binding groove. They can be defined as follows: region 1, beta-beta contacts in the helix of the beta1 domain; region 2, alpha-alpha contacts near the alpha 1/alpha2 domain junction and region 3; alpha-beta contacts in the alpha2/beta2 domains adjacent to the plasma membrane. To determine whether salt bridges and polar interactions formed within these regions are involved in the immune function of the murine MHC class II molecule, I-A(b), appropriate residues in both the alpha and beta chain were identified and mutated to uncharged alanine. Cell lines transfected with different combinations of mutated alpha and beta chains were generated and tested for MHC class II expression, peptide binding capabilities, and ability to present antigenic peptide to an OVA-specific T cell hybridoma. With the exception of two residues in region 2, the substitutions tested did not modulate MHC class II expression, or peptide binding function. When tested for ability to present peptide to an antigen-specific T cell hybridoma, with the exception of mutations in region 2, the substitutions did not appear to abrogate the ability of I-A(b) to stimulate the T cells. These results suggest that mutation of residues in region 2 of the putative superdimer interface have a gross effect on the ability of I-A(b) to be expressed on the cell surface. However, abrogation of salt bridges in region 1 and 3 do not influence I-A(b) cell surface expression, peptide binding or ability to

  16. Structure, regulation, and putative function of the arginine deiminase system of Streptococcus suis.

    Science.gov (United States)

    Gruening, Petra; Fulde, Marcus; Valentin-Weigand, Peter; Goethe, Ralph

    2006-01-01

    Streptococcus suis is an important cause of infectious diseases in young pigs. Little is known about the virulence factors or protective antigens of S. suis. Recently, we have identified two proteins of the arginine deiminase system (ADS) of S. suis, which were temperature induced and expressed on the streptococcal surface (N. Winterhoff, R. Goethe, P. Gruening, M. Rohde, H. Kalisz, H. E. Smith, and P. Valentin-Weigand, J. Bacteriol. 184:6768-6776, 2002). In the present study, we analyzed the complete ADS of S. suis. Due to their homologies to the recently published S. gordonii ADS genes, the genes for arginine deiminase, ornithine carbamoyl-transferase, and carbamate kinase, which were previously designated adiS, octS, and ckS, respectively, were renamed arcA, arcB, and arcC, respectively. Our data revealed that arcA, arcB, and arcC of the S. suis ADS are transcribed from an operon (arcABC operon). Additionally, putative ADS-associated genes were cloned and sequenced which, however, did not belong to the arcABC operon. These were the flpS gene upstream of the arcABC operon with homology to the flp transcription regulator of S. gordonii and the arcD, arcT, arcH, and argR genes downstream of the arcABC operon with high homologies to a putative arginine-ornithine antiporter, a putative dipeptidase of S. gordonii, a putative beta-N-acetylhexosaminidase of S. pneumoniae, and a putative arginine repressor of S. gordonii, respectively. The transcriptional start point of the arcABC operon was determined, and promoter analysis provided evidence that multiple factors contribute to the regulation of the ADS. Thus, a putative binding site for a transcription regulator of the Crp/Fnr family, an ArgR-binding site, and two cis-acting catabolite response elements were identified in the promoter-operator region of the operon. Consistent with this, we could demonstrate that the ADS of S. suis is inducible by arginine and reduced O2 tension and subject to carbon catabolite

  17. Identification of New Diterpenes as Putative Marker Compounds Distinguishing Agnus Castus Fruit (Chaste Tree) from Shrub Chaste Tree Fruit (Viticis Fructus).

    Science.gov (United States)

    Oshima, Naohiro; Masada, Sayaka; Suzuki, Ryuta; Yagi, Kanae; Matsufuji, Hiroshi; Suenaga, Emi; Takahashi, Yutaka; Yahagi, Tadahiro; Watanabe, Masato; Yahara, Shoji; Iida, Osamu; Kawahara, Nobuo; Maruyama, Takuro; Goda, Yukihiro; Hakamatsuka, Takashi

    2016-01-01

    Agnus Castus Fruit is defined in the European Pharmacopoeia as the dried ripe fruit of Vitex agnus-castus. In Europe it is used as a medicine targeting premenstrual syndrome and climacteric disorder. In Japan, Agnus Castus Fruit is becoming popular as a raw material for over-the-counter drugs and health food products, though its congenic species, Vitex rotundifolia and Vitex trifolia, have been used as Shrub Chaste Tree Fruit in traditional medicines. Therefore, it is important to discriminate these Vitex plants from the viewpoint of regulatory science. Here we tried to identify putative marker compounds that distinguish between Agnus Castus Fruit and Shrub Chaste Tree Fruit. We analyzed extracts of each crude drug by liquid chromatography-mass spectrometry, and performed differential analysis by comparison of each chromatogram to find one or more peaks characteristic of Agnus Castus Fruit. A peak was isolated and identified as an equilibrium mixture of new compounds named chastol (1) and epichastol (1a). The planar structures of 1 and 1a were determined spectroscopically. Their relative configurations were revealed by nuclear Overhauser effect spectroscopy and differential nuclear Overhauser effect-NMR data. Since avoiding contamination from closely related species is needed for the quality control of natural pharmaceuticals, this information will be valuable to establish a method for the quality control of both, Agnus Castus Fruit and Shrub Chaste Tree Fruit products.

  18. Functional characterization of a putative β-lactamase gene in the genome of Zymomonas mobilis.

    Science.gov (United States)

    Rajnish, K Narayanan; Asraf, Sheik Abdul Kader Sheik; Manju, Nagarajan; Gunasekaran, Paramasamy

    2011-12-01

    Zymomonas mobilis ZM4 is resistant to β-lactam antibiotics but there are no reports of a β-lactam resistance gene and its regulation. A putative β-lactamase gene sequence (ZMO0103) in the genome of Z. mobilis showed a 55% amino acid sequence identity with class C β-lactamase genes. qPCR analysis of the β-lactamase transcript indicated a higher level expression of the β-lactamase compared to the relative transcript quantities in antibiotic-susceptible bacteria. The putative β-lactamase gene was cloned, expressed in Escherichia coli BL21 and the product, AmpC, was purified to homogeneity. Its optimal activity was at pH 6 and 30 °C. Further, the β-lactamase had a higher affinity towards penicillins than cephalosporin antibiotics. © Springer Science+Business Media B.V. 2011

  19. Identification and functional characterization of a putative IDE, C28F5.4 (ceIDE-1), in Caenorhabditis elegans: Implications for Alzheimer's disease.

    Science.gov (United States)

    Haque, Rizwanul; Nazir, Aamir

    2016-11-01

    Insulin-degrading enzyme (IDE) is a zinc metalloprotease, known to degrade insulin peptide and amyloid-beta (Aβ); the key protein involved in Alzheimer's disease (AD). Considering the important role played by IDE in disease progression of AD and type 2 diabetes mellitus (T2DM), we endeavored to identify the Caenorhabditis elegans (C. elegans) IDE orthologous genes and test them for their role in AD related outcomes. We employed bioinformatics, reverse genetics and molecular biology approaches towards identification and functional characterization of putative IDE candidates in C. elegans. Using in-silico analysis we have identified seven C. elegans genes that possess HXXEH motif, an identifying marker of IDE. We further carried out functional analysis of the identified genes in Aβ expressing C. elegans strain CL4176 [myo-3/Aβ1-42 long 3'-UTR] via studying effect on Aβ induced toxicity, cholinergic neuroanatomy, content of acetylcholine/acetylcholine-esterase, extent of reactive oxygen species and expression of FOXO transcription factor DAF-16. Our findings reveal that amongst the identified putative IDE orthologs, a functionally uncharacterized gene C28F5.4 had a profound effect on the tested endpoints. Knocking down C28F5.4 modulated the AD associated conditions by decreasing Aβ induced toxicity, severely compromising cholinergic neuroanatomy, reducing expression of acetylcholine-transporter, decreasing acetylcholine content, elevating ROS, with no effect on DAF-16 stress-response protein. These studies provide crucial insight into the structural/functional orthology of IDEs across human and nematode species and further our understanding of the involvement of these proteins and insulin pathway in AD. Further studies could aid in identifying novel drug-targets and in understanding the common modulating factors between AD and T2DM.

  20. Nested Association Mapping for Identification of Functional Markers

    Science.gov (United States)

    Guo, Baohong; Sleper, David A.; Beavis, William D.

    2010-01-01

    Identification of functional markers (FMs) provides information about the genetic architecture underlying complex traits. An approach that combines the strengths of linkage and association mapping, referred to as nested association mapping (NAM), has been proposed to identify FMs in many plant species. The ability to identify and resolve FMs for complex traits depends upon a number of factors including frequency of FM alleles, magnitudes of their genetic effects, disequilibrium among functional and nonfunctional markers, statistical analysis methods, and mating design. The statistical characteristics of power, accuracy, and precision to identify FMs with a NAM population were investigated using three simulation studies. The simulated data sets utilized publicly available genetic sequences and simulated FMs were identified using least-squares variable selection methods. Results indicate that FMs with simple additive genetic effects that contribute at least 5% to the phenotypic variability in at least five segregating families of a NAM population consisting of recombinant inbred progeny derived from 28 matings with a single reference inbred will have adequate power to accurately and precisely identify FMs. This resolution and power are possible even for genetic architectures consisting of disequilibrium among multiple functional and nonfunctional markers in the same genomic region, although the resolution of FMs will deteriorate rapidly if more than two FMs are tightly linked within the same amplicon. Finally, nested mating designs involving several reference parents will have a greater likelihood of resolving FMs than single reference designs. PMID:20551444

  1. Identification and functional analysis of Penicillium digitatum genes putatively involved in virulence towards citrus fruit.

    Science.gov (United States)

    López-Pérez, Mario; Ballester, Ana-Rosa; González-Candelas, Luis

    2015-04-01

    The fungus Penicillium digitatum, the causal agent of green mould rot, is the most destructive post-harvest pathogen of citrus fruit in Mediterranean regions. In order to identify P. digitatum genes up-regulated during the infection of oranges that may constitute putative virulence factors, we followed a polymerase chain reaction (PCR)-based suppression subtractive hybridization and cDNA macroarray hybridization approach. The origin of expressed sequence tags (ESTs) was determined by comparison against the available genome sequences of both organisms. Genes coding for fungal proteases and plant cell wall-degrading enzymes represent the largest categories in the subtracted cDNA library. Northern blot analysis of a selection of P. digitatum genes, including those coding for proteases, cell wall-related enzymes, redox homoeostasis and detoxification processes, confirmed their up-regulation at varying time points during the infection process. Agrobacterium tumefaciens-mediated transformation was used to generate knockout mutants for two genes encoding a pectin lyase (Pnl1) and a naphthalene dioxygenase (Ndo1). Two independent P. digitatum Δndo1 mutants were as virulent as the wild-type. However, the two Δpnl1 mutants analysed were less virulent than the parental strain or an ectopic transformant. Together, these results provide a significant advance in our understanding of the putative determinants of the virulence mechanisms of P. digitatum.

  2. Functional characterization of PaLAX1, a putative auxin permease, in heterologous plant systems.

    Science.gov (United States)

    Hoyerová, Klára; Perry, Lucie; Hand, Paul; Lanková, Martina; Kocábek, Tomás; May, Sean; Kottová, Jana; Paces, Jan; Napier, Richard; Zazímalová, Eva

    2008-03-01

    We have isolated the cDNA of the gene PaLAX1 from a wild cherry tree (Prunus avium). The gene and its product are highly similar in sequences to both the cDNAs and the corresponding protein products of AUX/LAX-type genes, coding for putative auxin influx carriers. We have prepared and characterized transformed Nicotiana tabacum and Arabidopsis thaliana plants carrying the gene PaLAX1. We have proved that constitutive overexpression of PaLAX1 is accompanied by changes in the content and distribution of free indole-3-acetic acid, the major endogenous auxin. The increase in free indole-3-acetic acid content in transgenic plants resulted in various phenotype changes, typical for the auxin-overproducing plants. The uptake of synthetic auxin, 2,4-dichlorophenoxyacetic acid, was 3 times higher in transgenic lines compared to the wild-type lines and the treatment with the auxin uptake inhibitor 1-naphthoxyacetic acid reverted the changes caused by the expression of PaLAX1. Moreover, the agravitropic response could be restored by expression of PaLAX1 in the mutant aux1 plants, which are deficient in auxin influx carrier activity. Based on our data, we have concluded that the product of the gene PaLAX1 promotes the uptake of auxin into cells, and, as a putative auxin influx carrier, it affects the content and distribution of free endogenous auxin in transgenic plants.

  3. Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants.

    Science.gov (United States)

    Duan, Jubao; Sanders, Alan R; Moy, Winton; Drigalenko, Eugene I; Brown, Eric C; Freda, Jessica; Leites, Catherine; Göring, Harald H H; Gejman, Pablo V

    2015-08-15

    We searched a gene expression dataset comprised of 634 schizophrenia (SZ) cases and 713 controls for expression outliers (i.e., extreme tails of the distribution of transcript expression values) with SZ cases overrepresented compared with controls. These outlier genes were enriched for brain expression and for genes known to be associated with neurodevelopmental disorders. SZ cases showed higher outlier burden (i.e., total outlier events per subject) than controls for genes within copy number variants (CNVs) associated with SZ or neurodevelopmental disorders. Outlier genes were enriched for CNVs and for rare putative regulatory variants, but this only explained a small proportion of the outlier subjects, highlighting the underlying presence of additional genetic and potentially, epigenetic mechanisms.

  4. Functional characterization of the bladder cancer marker, BLCA-4.

    Science.gov (United States)

    Van Le, Thu-Suong; Myers, Julie; Konety, Badrinath R; Barder, Timothy; Getzenberg, Robert H

    2004-02-15

    Bladder cancer is a common disease of the genitourinary tract for which the development of a noninvasive detection technique would have a significant impact on disease management. One of our previously identified bladder cancer-specific proteins, BLCA-4, appears to be associated with a "field effect" of the disease, and in clinical trials is able to separate individuals with bladder cancer from those without the disease with high sensitivity and specificity. The potential clinical utility of this marker has led to the analysis of its function in bladder cancer pathobiology. To additionally analyze the specificity of this marker, the expression in the urine of a variety of benign urologic conditions was analyzed. After cloning the gene encoding BLCA-4, functional aspects of the protein were analyzed by overexpressing it in cell systems, as well as its interaction with other transcription factors and in gel mobility shift assays. Finally, to determine the timing of expression in relation to the observance of bladder cancer, an animal model of the disease was examined. Expression of BLCA-4, the cDNA of which reveals that it is a novel member of the ETS transcription factor family, is not found in benign urologic conditions. Overexpression leads to increased growth rates of cells, and the protein interacts with other transcription factors. In vivo studies reveal that BLCA-4 expression occurs significantly before the observance of grossly visible tumors in an animal model of the disease. BLCA-4 is a bladder cancer marker that is highly specific and occurs early in the development of the disease. It appears to be a transcription factor that may play a role in the regulation of the gene expression in bladder cancer. BLCA-4 is a marker with significant clinical utility that may have an active role in the disease.

  5. The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.; Gomes Guimaraes, B.

    2008-01-01

    Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstroms resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.

  6. Functional Characterization of a Putative Nitrate Transporter Gene Promoter from Rice

    Institute of Scientific and Technical Information of China (English)

    Ting-Zhang HU; Kai-Ming CAO; Mian XIA; Xi-Ping WANG

    2006-01-01

    Drought is one of the most significant abiotic stresses that influence plant growth and development. Expression analysis revealed that OsNRT1.3, a putative nitrate transporter gene in rice, was induced by drought. To confirm if the OsNRT1.3 promoter can respond to drought stress, a 2019 bp upstream sequence of OsNRT1.3 was cloned. Three OsNRT1.3 promoter fragments were generated by 5'-deletion, and fused to the β-glucuronidase (GUS) gene. The chimeric genes were introduced into rice plants. NRT2019::GUS, NRT1196: :GUS and NRT719::GUS showed similar expression patterns in seeds,roots, leaves and flowers in all transgenic rice, and GUS activity conferred by different OsNRT1.3 promoter fragments was significantly upregulated by drought stress, indicating that OsNRT1.3 promoter responds to drought stress and the 719 bp upstream sequence of OsNRT1.3 contains the drought response elements.

  7. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  8. Functional analysis of putative phosphoenolpyruvate transporters localized to the Golgi apparatus in Schizosaccharomyces pombe.

    Science.gov (United States)

    Yoritsune, Ken-ichi; Higuchi, Yujiro; Matsuzawa, Tomohiko; Takegawa, Kaoru

    2014-11-01

    The cell surface of Schizosaccharomyces pombe is negatively charged due to the presence of pyruvylated oligosaccharides, which is important for cell-cell recognition. However, the mechanism of pyruvate supply to oligosaccharides is not clearly understood. Here, we analyzed three putative phosphoenolpyruvate (PEP) transporter genes (pet1(+) , pet2(+) , and pet3(+) ) in S. pombe, identified by sequence homology search against the Arabidopsis thaliana PEP transporter AtPPT1. Schizosaccharomyces pombe strain carrying a disruption in pet1(+) (pet1Δ) or in pet2(+) (pet2Δ), but not the strain carrying a disruption in pet3(+) (pet3Δ), showed reduced pyruvate level on the cell surface. This reduction in pyruvate level was restored to the control level by expressing green fluorescent protein (GFP)-tagged Pet1p and Pet2p in respective disruptants. Fluorescence microscope studies revealed that GFP-tagged Pet1p and Pet2p were localized to the Golgi apparatus. Although expression of neither AtPPT1 nor AtPPT2 suppressed the pet1Δ phenotype, that of chimeric constructs, where the N-terminal regions of AtPPT1 and AtPPT2 were replaced by the N-terminal region of Pet1p, partially suppressed the pet1Δ phenotype. Furthermore, the reduction in cell surface negative charge in pet1Δ cells was restored by incubating these cells with recombinant Pvg1p and PEP. Thus, Pet1p and Pet2p are likely involved in transporting PEP from the cytoplasm into the Golgi.

  9. Monitoring aromatic hydrocarbon biodegradation by functional marker genes

    Energy Technology Data Exchange (ETDEWEB)

    Nyyssoenen, Mari [Technical Research Centre of Finland, Espoo (Finland)], E-mail: mari.nyyssonen@vtt.fi; Piskonen, Reetta; Itaevaara, Merja [Technical Research Centre of Finland, Espoo (Finland)

    2008-07-15

    The development of biological treatment technologies for contaminated environments requires tools for obtaining direct information about the biodegradation of specific contaminants. The potential of functional gene array analysis to monitor changes in the amount of functional marker genes as indicators of contaminant biodegradation was investigated. A prototype functional gene array was developed for targeting key functions in the biodegradation of naphthalene, toluene and xylenes. Internal standard probe based normalization was introduced to facilitate comparison across multiple samples. Coupled with one-colour hybridization, the signal normalization improved the consistency among replicate hybridizations resulting in better discrimination for the differences in the amount of target DNA. During the naphthalene biodegradation in a PAH-contaminated soil slurry microcosm, the normalized hybridization signals in naphthalene catabolic gene probes were in good agreement with the amount of naphthalene-degradation genes and the production of {sup 14}CO{sub 2}. Gene arrays provide efficient means for monitoring of contaminant biodegradation in the environment. - Functional gene array analysis coupled with one-colour hybridization and internal standard based signal normalization provides efficient tool for monitoring contaminant biodegradation processes.

  10. Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets

    Directory of Open Access Journals (Sweden)

    Chirumbolo Salvatore

    2010-09-01

    Full Text Available Abstract Background Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release. Results Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism. Conclusions These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.

  11. Human 2'-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover

    DEFF Research Database (Denmark)

    Poulsen, Jesper Buchhave; Andersen, Kasper Røjkjær; Kjær, Karina Hansen

    2011-01-01

    . Interestingly, 2′-PDE shares both functionally and structurally characteristics with the CCR4-type exonuclease–endonuclease–phosphatase family of deadenylases. Here we show that 2′-PDE locates to the mitochondrial matrix of human cells, and comprise an active 3′–5′ exoribonuclease exhibiting a preference...... a role in the cellular immune system, may also function in mitochondrial RNA turnover....

  12. Exploring Identity-By-Descent Segments and Putative Functions Using Different Foundation Parents in Maize

    Science.gov (United States)

    Wu, Xun; Li, Yongxiang; Fu, Junjie; Li, Xin; Li, Chunhui; Zhang, Dengfeng; Shi, Yunsu; Song, Yanchun; Li, Yu; Wang, Tianyu

    2016-01-01

    Maize foundation parents (FPs) play no-alternative roles in hybrid breeding because they were widely used in the development of new lines and hybrids. The combination of different identity-by-descent (IBD) segments and genes could account for the formation patterns of different FPs, and knowledge of these IBD regions would provide an extensive foundation for the development of new candidate FP lines in future maize breeding. In this paper, a panel of 304 elite lines derived from FPs, i.e., B73, 207, Mo17, and Huangzaosi (HZS), was collected and analyzed using 43,252 single nucleotide polymorphism (SNP) markers. Most IBD segments specific to particular FP groups were identified, including 116 IBD segments in B73, 105 in Mo17, 111 in 207, and 190 in HZS. In these regions, 423 quantitative trait nucleotides (QTNs) associated with 15 agronomic traits and 804 candidate genes were identified. Some known adaptation-related genes, e.g., dwarf8 and vgt1 in HZS, zcn8 and epc in Mo17, and ZmCCT in 207, were validated as being tightly linked to particular IBD segments. In addition, numerous new candidate genes were also identified. For example, GRMZM2G154278 in HZS, which belongs to the cell cycle control family, was closely linked to a QTN of the ear height/plant height (EH/PH) trait; GRMZM2G051943 in 207, which encodes an endochitinase precursor (EP) chitinase, was closely linked to a QTN for kernel density; and GRMZM2G170586 in Mo17 was closely linked to a QTN for ear diameter. Complex correlations among these genes were also found. Many IBD segments and genes were included in the formation of FP lines, and complex regulatory networks exist among them. These results provide new insights on the genetic basis of complex traits and provide new candidate IBD regions or genes for the improvement of special traits in maize production. PMID:27997600

  13. Repression of estrogen receptor {beta} function by putative tumor suppressor DBC1

    Energy Technology Data Exchange (ETDEWEB)

    Koyama, Satoshi [Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan); Wada-Hiraike, Osamu, E-mail: osamuwh-tky@umin.ac.jp [Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan); Nakagawa, Shunsuke; Tanikawa, Michihiro; Hiraike, Haruko; Miyamoto, Yuichiro; Sone, Kenbun; Oda, Katsutoshi [Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan); Fukuhara, Hiroshi [Department of Urology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan); Nakagawa, Keiichi [Department of Radiology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan); Kato, Shigeaki [SORST, Japan Science and Technology, Honcho 4-1-8, Kawaguchi, Saitama 332-0012 (Japan); Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1 Bunkyo-ku, Tokyo 113-0034 (Japan); Yano, Tetsu; Taketani, Yuji [Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo 113-8655 (Japan)

    2010-02-12

    It has been well established that estrogen is involved in the pathophysiology of breast cancer. Estrogen receptor (ER) {alpha} appears to promote the proliferation of cancer tissues, while ER{beta} can protect against the mitogenic effect of estrogen in breast tissue. The expression status of ER{alpha} and ER{beta} may greatly influence on the development, treatment, and prognosis of breast cancer. Previous studies have indicated that the deleted in breast cancer 1 (DBC1/KIAA1967) gene product has roles in regulating functions of nuclear receptors. The gene encoding DBC1 is a candidate for tumor suppressor identified by genetic search for breast cancer. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of the endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. In addition, DBC1 modulates ER{alpha} expression and promotes breast cancer cell survival by binding to ER{alpha}. Here we report an ER{beta}-specific repressive function of DBC1. Immunoprecipitation and immunofluorescence studies show that ER{beta} and DBC1 interact in a ligand-independent manner similar to ER{alpha}. In vitro pull-down assays revealed a direct interaction between DBC1 amino-terminus and activation function-1/2 domain of ER{beta}. Although DBC1 shows no influence on the ligand-dependent transcriptional activation function of ER{alpha}, the expression of DBC1 negatively regulates the ligand-dependent transcriptional activation function of ER{beta}in vivo, and RNA interference-mediated depletion of DBC1 stimulates the transactivation function of ER{beta}. These results implicate the principal role of DBC1 in regulating ER{beta}-dependent gene expressions.

  14. Computer-Based Annotation of Putative AraC/XylS-Family Transcription Factors of Known Structure but Unknown Function

    Directory of Open Access Journals (Sweden)

    Andreas Schüller

    2012-01-01

    Full Text Available Currently, about 20 crystal structures per day are released and deposited in the Protein Data Bank. A significant fraction of these structures is produced by research groups associated with the structural genomics consortium. The biological function of many of these proteins is generally unknown or not validated by experiment. Therefore, a growing need for functional prediction of protein structures has emerged. Here we present an integrated bioinformatics method that combines sequence-based relationships and three-dimensional (3D structural similarity of transcriptional regulators with computer prediction of their cognate DNA binding sequences. We applied this method to the AraC/XylS family of transcription factors, which is a large family of transcriptional regulators found in many bacteria controlling the expression of genes involved in diverse biological functions. Three putative new members of this family with known 3D structure but unknown function were identified for which a probable functional classification is provided. Our bioinformatics analyses suggest that they could be involved in plant cell wall degradation (Lin2118 protein from Listeria innocua, PDB code 3oou, symbiotic nitrogen fixation (protein from Chromobacterium violaceum, PDB code 3oio, and either metabolism of plant-derived biomass or nitrogen fixation (protein from Rhodopseudomonas palustris, PDB code 3mn2.

  15. Review of Functional Markers for Improving Cooking, Eating and the Nutritional Qualities of Rice

    Directory of Open Access Journals (Sweden)

    Wendy Chui Phing Lau

    2015-10-01

    Full Text Available After yield, quality is one of the most important aspects of rice breeding. Preference for rice quality varies among cultures and regions; therefore, rice breeders have to tailor the quality according to the preferences of local consumers. Rice quality assessment requires routine chemical analysis procedures. The advancement of molecular marker technology has revolutionized the strategy in breeding programs. The availability of rice genome sequences and the use of forward and reverse genetics approaches facilitate gene discovery and the deciphering of gene functions. A well-characterized gene is the basis for the development of functional markers, which play an important role in plant genotyping and, in particular, marker-assisted breeding. In addition, functional markers offer advantages that counteract the limitations of random DNA markers. Some functional markers have been applied in marker-assisted breeding programs and have successfully improved rice quality to meet local consumers’ preferences. Although functional markers offer a plethora of advantages over random genetic markers, the development and application of functional markers should be conducted with care. The decreasing cost of sequencing will enable more functional markers for rice quality improvement to be developed, and application of these markers in rice quality breeding programs is highly anticipated.

  16. Mucositis and non-invasive markers of small intestinal function.

    Science.gov (United States)

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  17. Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart.

    Directory of Open Access Journals (Sweden)

    Simon R Foster

    Full Text Available G protein-coupled receptors (GPCRs are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2 as well as Tas1r1 and Tas1r3 (comprising the umami receptor are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1(Cre/Rosa26(tdRFP strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

  18. Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Schnabel Philipp A

    2011-05-01

    Full Text Available Abstract Background Aquaporins (AQPs have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs. Methods We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry. Results Variable expression of several AQPs (AQP1, -3, -4, and -5 was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue. Conclusions Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.

  19. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    Science.gov (United States)

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele

    2011-04-01

    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  20. A novel TNF-inducible message with putative growth suppressor function.

    Science.gov (United States)

    Nadadur, S S; Ehrke, M J; Gurtoo, H L

    1999-12-23

    We report the nucleotide sequence of a novel cDNA and TNF-induced expression of the corresponding message (mRNA) in human fibroblast cells. This message is also expressed in certain human tumor cell lines and is over-expressed in a colon cancer cell line (HT-29). NIH3T3 cells transfected with the antisense construct of the 5'-region of this novel cDNA formed 20-fold more colonies in culture compared to cells transfected with a sense construct of the same region or the sense and the antisense constructs of the central region of this cDNA. This observation suggests a possible growth suppressor function for the gene represented by this cDNA.

  1. Expression analysis of Arabidopsis vacuolar sorting receptor 3 reveals a putative function in guard cells.

    Science.gov (United States)

    Avila, Emily L; Brown, Michelle; Pan, Songqin; Desikan, Radhika; Neill, Steven J; Girke, Thomas; Surpin, Marci; Raikhel, Natasha V

    2008-01-01

    Vacuolar sorting receptors (VSRs) are responsible for the proper targeting of soluble cargo proteins to their destination compartments. The Arabidopsis genome encodes seven VSRs. In this work, the spatio-temporal expression of one of the members of this gene family, AtVSR3, was determined by RT-PCR and promoter::reporter gene fusions. AtVSR3 was expressed specifically in guard cells. Consequently, a reverse genetics approach was taken to determine the function of AtVSR3 by using RNA interference (RNAi) technology. Plants expressing little or no AtVSR3 transcript had a compressed life cycle, bolting approximately 1 week earlier and senescing up to 2 weeks earlier than the wild-type parent line. While the development and distribution of stomata in AtVSR3 RNAi plants appeared normal, stomatal function was altered. The guard cells of mutant plants did not close in response to abscisic acid treatment, and the mean leaf temperatures of the RNAi plants were on average 0.8 degrees C lower than both wild type and another vacuolar sorting receptor mutant, atvsr1-1. Furthermore, the loss of AtVSR3 protein caused the accumulation of nitric oxide and hydrogen peroxide, signalling molecules implicated in the regulation of stomatal opening and closing. Finally, proteomics and western blot analyses of cellular proteins isolated from wild-type and AtVSR3 RNAi leaves showed that phospholipase Dgamma, which may play a role in abscisic acid signalling, accumulated to higher levels in AtVSR3 RNAi guard cells. Thus, AtVSR3 may play an important role in responses to plant stress.

  2. Bacterial associates of arboreal ants and their putative functions in an obligate ant-plant mutualism.

    Science.gov (United States)

    Eilmus, Sascha; Heil, Martin

    2009-07-01

    Bacterial communities are highly diverse and have great ecological importance. In the present study, we used an in silico analysis of terminal restriction fragments (tRF) to characterize the bacterial community of the plant ant Pseudomyrmex ferrugineus. This species is an obligate inhabitant of Acacia myrmecophytes and feeds exclusively on plant-derived food sources. Ants are the dominant insect group in tropical rain forests. Associations of ants with microbes, which contribute particularly to the ants' nitrogen nutrition, could allow these insects to live on mostly or entirely plant-based diets and could thus contribute to the explanation of the high abundances that are reached by tropical ants. We found tRF patterns representing at least 30 prokaryotic taxa, of which the Acidobacteria, Actinobacteria, Bacteroidetes, Firmicutes, Planctomycetes, Proteobacteria, and Spirochaetes comprised 93%. Because most bacterial taxa were found in all ant-derived samples studied and because the bacteria detected on the ants' host plant revealed little overlap with this community, we regard our results as reliably representing the bacterial community that is associated with P. ferrugineus. Genera with a likely function as ant symbionts were Burkholderia, Pantoea, Weissella, and several members of the Enterobacteriaceae. The presence of these and various other groups was confirmed via independent PCR and cultivation approaches. Many of the bacteria that we detected belong to purportedly N-fixing taxa. Bacteria may represent important further partners in ant-plant mutualisms, and their influences on ant nutrition can contribute to the extraordinary abundance and evolutionary success of tropical arboreal ants.

  3. Analysis of the Putative Role of CR1 in Alzheimer's Disease: Genetic Association, Expression and Function.

    Directory of Open Access Journals (Sweden)

    Maria I Fonseca

    Full Text Available Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD. Recent large genome wide association studies (GWAS have identified single nucleotide polymorphisms (SNPs in the C3b/C4b receptor (CR1 or CD35 that are associated with late onset AD. Here, anti-CR1 antibodies (Abs directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1 regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved.

  4. Functional importance of GGXG sequence motifs in putative reentrant loops of 2HCT and ESS transport proteins.

    Science.gov (United States)

    Dobrowolski, Adam; Lolkema, Juke S

    2009-08-11

    The 2HCT and ESS families are two families of secondary transporters. Members of the two families are unrelated in amino acid sequence but share similar hydropathy profiles, which suggest a similar folding of the proteins in membranes. Structural models show two homologous domains containing five transmembrane segments (TMSs) each, with a reentrant or pore loop between the fourth and fifth TMSs in each domain. Here we show that GGXG sequence motifs present in the putative reentrant loops are important for the activity of the transporters. Mutation of the conserved Gly residues to Cys in the motifs of the Na(+)-citrate transporter CitS in the 2HCT family and the Na(+)-glutamate transporter GltS in the ESS family resulted in strongly reduced transport activity. Similarly, mutation of the variable residue "X" to Cys in the N-terminal half of GltS essentially inactivated the transporter. The corresponding mutations in the N- and C-terminal halves of CitS reduced transport activity to 60 and 25% of that of the wild type, respectively. Residual activity of any of the mutants could be further reduced by treatment with the membrane permeable thiol reagent N-ethylmaleimide (NEM). The X to Cys mutation (S405C) in the cytoplasmic loop in the C-terminal half of CitS rendered the protein sensitive to the bulky, membrane impermeable thiol reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AmdiS) added at the periplasmic side of the membrane, providing further evidence that this part of the loop is positioned between the transmembrane segments. The putative reentrant loop in the C-terminal half of the ESS family does not contain the GGXG motif, but a conserved stretch rich in Gly residues. Cysteine-scanning mutagenesis of a stretch of 18 residues in the GltS protein revealed two residues important for function. Mutant N356C was completely inactivated by treatment with NEM, and mutant P351C appeared to be the counterpart of mutant S405C of CitS; the mutant was

  5. Maternal blood metal levels and fetal markers of metabolic function

    Energy Technology Data Exchange (ETDEWEB)

    Ashley-Martin, Jillian [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Dodds, Linda, E-mail: l.dodds@dal.ca [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Arbuckle, Tye E. [Health Canada, Ottawa (Canada); Ettinger, Adrienne S. [Yale University, New Haven, CT (United States); Shapiro, Gabriel D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada); Fisher, Mandy [Health Canada, Ottawa (Canada); Taback, Shayne [University of Manitoba, Winnipeg, Manitoba (Canada); Bouchard, Maryse F. [University of Montreal, Montreal, Quebec (Canada); Monnier, Patricia [McGill University, Montreal, Quebec (Canada); Dallaire, Renee [Laval University, Quebec City, Quebec (Canada); Fraser, William D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada)

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  6. Expression pattern of pluripotent markers in different embryonic developmental stages of buffalo (Bubalus bubalis) embryos and putative embryonic stem cells generated by parthenogenetic activation.

    Science.gov (United States)

    Singh, Karn P; Kaushik, Ramakant; Garg, Veena; Sharma, Ruchi; George, Aman; Singh, Manoj K; Manik, Radhey S; Palta, Prabhat; Singla, Suresh K; Chauhan, Manmohan S

    2012-12-01

    In this study, we describe the production of buffalo parthenogenetic blastocysts and subsequent isolation of parthenogenetic embryonic stem cell (PGESC)-like cells. PGESC colonies exhibited dome-shaped morphology and were clearly distinguishable from the feeder layer cells. Different stages of development of parthenogenetic embryos and derived embryonic stem cell (ESC)-like cells expressed key ESC-specific markers, including OCT-4, NANOG, SOX-2, FOXD3, REX-1, STAT-3, TELOMERASE, NUCLEOSTEMIN, and cMYC. Immunofluorescence-based studies revealed that the PGESCs were positive for surface-based pluripotent markers, viz., SSEA-3, SSEA-4, TRA 1-80, TRA 1-60, CD-9, and CD-90 and exhibited high alkaline phosphatase (ALP) activity. PGEC cell-like cells formed embryoid body (EB)-like structures in hanging drop cultures and when cultured for extended period of time spontaneously differentiated into derivatives of three embryonic germ layers as confirmed by RT-PCR for ectodermal (CYTOKERATIN8, NF-68), mesodermal (MSX1, BMP-4, ASA), and endodermal markers (AFP, HNF-4, GATA-4). Differentiation of PGESCs toward the neuronal lineage was successfully directed by supplementation of serum-containing media with retinoic acid. Our results indicate that the isolated ESC-like cells from parthenogenetic blastocyst hold properties of ESCs and express markers of pluripotency. The pluripotency markers were also expressed by early cleavage-stage of buffalo embryos.

  7. Identification and functional characterization of the putative polysaccharide biosynthesis protein (CapD) of Enterococcus faecium U0317.

    Science.gov (United States)

    Ali, Liaqat; Spiess, Meike; Wobser, Dominique; Rodriguez, Marta; Blum, Hubert E; Sakιnç, Türkân

    2016-01-01

    Most bacterial species produce capsular polysaccharides that contribute to disease pathogenesis through evasion of the host innate immune system and are also involved in inhibiting leukocyte killing. In the present study, we identified a gene in Enterococcus faecium U0317 with homologies to the polysaccharide biosynthesis protein CapD that is made up of 336 amino acids and putatively catalyzes N-linked glycosylation. A capD deletion mutant was constructed and complemented by homologous recombination that was confirmed by PCR and sequencing. The mutant revealed different growth behavior and morphological changes compared to wild-type by scanning electron microscopy, also the capD mutant showed a strong hydrophobicity and that was reversed in the reconstituted mutant. For further characterization and functional analyses, in-vitro cell culture and in-vivo a mouse infection models were used. Antibodies directed against alpha lipotechoic acid (αLTA) and the peptidyl-prolyl cis-trans isomerase (αPpiC), effectively mediated the opsonophagocytic killing in the capD knock-out mutant, while this activity was not observed in the wild-type and reconstituted mutant. By comparison more than 2-fold decrease was seen in mutant colonization and adherence to both T24 and Caco2 cells. However, a significant higher bacterial colonization was observed in capD mutant during bacteremia in the animal model, while virulence in a mouse UTI (urinary tract infection) model, there were no obvious differences. Further studies are needed to elucidate the function of capsular polysaccharide synthesis gene clusters and its involvement in the disease pathogenesis with the aim to develop targeted therapies to treat multidrug-resistant E. faecium infections.

  8. Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ömer Aydemir

    2014-12-01

    Full Text Available Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502; household activities and superoxide dismutase (r = 0.501; participation in social activities and nitric oxide (r = 0.414; hobbies and leisure time activities and total glutathione (r = -0.567, superoxide dismutase (r = 0.667, and neurotrophin 4 (r = 0.450; and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597. There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

  9. An LTR Retrotransposon-Derived Gene Displays Lineage-Specific Structural and Putative Species-Specific Functional Variations in Eutherians

    Science.gov (United States)

    Irie, Masahito; Koga, Akihiko; Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2016-01-01

    Amongst the 11 eutherian-specific genes acquired from a sushi-ichi retrotransposon is the CCHC type zinc-finger protein-encoding gene SIRH11/ZCCHC16. Its contribution to eutherian brain evolution is implied because of its involvement in cognitive function in mice, possibly via the noradrenergic system. Although, the possibility that Sirh11/Zcchc16 functions as a non-coding RNA still remains, dN/dS ratios in pairwise comparisons between its orthologs have provided supportive evidence that it acts as a protein. It became a pseudogene in armadillos (Cingulata) and sloths (Pilosa), the only two extant orders of xenarthra, which prompted us to examine the lineage-specific variations of SIRH11/ZCCHC16 in eutherians. We examined the predicted SIRH11/ZCCHC16 open reading frame (ORF) in 95 eutherian species based on the genomic DNA information in GenBank. A large variation in the SIRH11/ZCCHC16 ORF was detected in several lineages. These include a lack of a CCHC RNA-binding domain in its C-terminus, observed in gibbons (Hylobatidae: Primates) and megabats (Megachiroptera: Chiroptera). A lack of the N-terminal half, on the other hand, was observed in New World monkeys (Platyrrhini: Primates) and species belonging to New World and African Hystricognaths (Caviomorpha and Bathyergidae: Rodents) along with Cetacea and Ruminantia (Cetartiodactyla). Among the hominoids, interestingly, three out of four genera of gibbons have lost normal SIRH11/ZCCHC16 function by deletion or the lack of the CCHC RNA-binding domain. Our extensive dN/dS analysis suggests that such truncated SIRH11/ZCCHC16 ORFs are functionally diversified even within lineages. Combined, our results show that SIRH11/ZCCHC16 may contribute to the diversification of eutherians by lineage-specific structural changes after its domestication in the common eutherian ancestor, followed by putative species-specific functional changes that enhanced fitness and occurred as a consequence of complex natural selection events

  10. Epidermal Cells Expressing Putative Cell Markers in Nonglabrous Skin Existing in Direct Proximity with the Distal End of the Arrector Pili Muscle

    Directory of Open Access Journals (Sweden)

    N. Torkamani

    2016-01-01

    Full Text Available Inconsistent with the view that epidermal stem cells reside randomly spread along the basal layer of the epidermal rete ridges, we found that epidermal cells expressing stem cell markers in nonglabrous skin exist in direct connection with the distal end of the arrector pili muscle. The epidermal cells that express stem cell markers consist of a subpopulation of basal keratinocytes located in a niche at the lowermost portion of the rete ridges at the distal arrector pili muscle attachment site. Keratinocytes in the epidermal stem cell niche express K15, MCSP, and α6 integrin. α5 integrin marks the distal end of the APM colocalized with basal keratinocytes expressing stem cell markers located in a well-protected and nourished environment at the lowermost point of the epidermis; these cells are hypothesized to participate directly in epidermal renewal and homeostasis and also indirectly in wound healing through communication with the hair follicle bulge epithelial stem cell population through the APM. Our findings, plus a reevaluation of the literature, support the hierarchical model of interfollicular epidermal stem cell units of Fitzpatrick. This new view provides insights into epidermal control and the possible involvement of epidermal stem cells in nonmelanoma skin carcinogenesis.

  11. Forms And Functions Relationships: Use Of Discourse Markers In ...

    African Journals Online (AJOL)

    Frederick Iraki

    therefore is simply an explicit signal of a specific relation between two or more propositions. .... The marker is produced by speaker A in his turn to change the topic ..... disagrees with the listener, the usage of DM serves as a positive politeness ...

  12. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10(-7)) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. The dtd gene from Bacillus amyloliquefaciens encodes a putative D-tyrosyl-tRNATyr deacylase and is a selectable marker for Bacillus subtilis.

    Science.gov (United States)

    Geraskina, Natalia V; Butov, Ivan A; Yomantas, Yurgis A V; Stoynova, Nataliya V

    2015-02-01

    Genetically engineered microbes are of high practical importance due to their cost-effective production of valuable metabolites and enzymes, and the search for new selectable markers for genetic manipulation is of particular interest. Here, we revealed that the soil bacterium Bacillus amyloliquefaciens A50 is tolerant to the non-canonical amino acid D-tyrosine (D-Tyr), in contrast to the closely related Bacillus strain B. subtilis 168, which is a widely used "domesticated" laboratory strain. The gene responsible for resistance to D-Tyr was identified. The resistance was associated with the activity of a potential D-tyrosyl-tRNA(Tyr) deacylase. Orthologs of this enzyme are capable of hydrolyzing the ester bond and recycling misacetylated D-aminoacyl-tRNA molecules into free tRNAs and D-amino acids. This gene, yrvI (dtd), is applicable as a convenient, small selectable marker for non-antibiotic resistance selection in experiments aimed at genome editing of D-Tyr-sensitive microorganisms.

  14. Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare)WRKY transcription factor family reveals putatively retained functions betweenmonocots and dicots

    Energy Technology Data Exchange (ETDEWEB)

    Mangelsen, Elke; Kilian, Joachim; Berendzen, Kenneth W.; Kolukisaoglu, Uner; Harter, Klaus; Jansson, Christer; Wanke, Dierk

    2008-02-01

    WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare), three different WRKY proteins have been characterized so far, as regulators in sucrose signaling, in pathogen defense, and in response to cold and drought, respectively. However, their phylogenetic relationship remained unresolved. In this study, we used the available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY) genes. According to their structural features the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs. HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in mono- and dicot species.

  15. Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare WRKY transcription factor family reveals putatively retained functions between monocots and dicots

    Directory of Open Access Journals (Sweden)

    Jansson Christer

    2008-04-01

    Full Text Available Abstract Background WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare, three different WRKY proteins have been characterized so far as regulators in sucrose signaling, pathogen defense, and in response to cold and drought. However, their phylogenetic relationship remained unresolved. Results In this study, we used available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY genes. According to their structural features, the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs. Conclusion HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in monocot and dicot species.

  16. Assessment of variation in antioxidative defense system in salt-treated pea (Pisum sativum) cultivars and its putative use as salinity tolerance markers.

    Science.gov (United States)

    Noreen, Zahra; Ashraf, Muhammad

    2009-11-01

    The present work describes whether the changes in the activities of antioxidant enzymes and the levels of some non-enzymatic antioxidants could be used as markers of salt tolerance in nine genetically diverse pea (Pisum sativum) cultivars. All cultivars were exposed to four levels of NaCl i.e., 0, 40, 80 and 120mM in sand culture. Plant fresh biomass, total phenolics, total soluble proteins, hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in leaves while different forms of tocopherols (alpha-, gamma- and Delta-tocopherol) in fresh seed of salt-stressed and non-stressed plants were analyzed. On the basis of percent inhibition in shoot biomass at the highest salt level (120mM) cultivars 2001-35, 2001-55 and Climax were ranked as tolerant (percent inhibition less than 60%), 2001-20, 9800-5 and 9800-10 moderately tolerant (percent inhibition 60-70%), and 2001-40, 9200 and Tere 2 salt sensitive (percent inhibition more than 70%). Salt stress markedly enhanced the activities of SOD and POD, levels of total phenolics and gamma- and Delta-tocopherols, and decreased the total soluble proteins and CAT activity, while the internal levels of H(2)O(2) remained unaffected in all pea cultivars. Although salt-induced oxidative stress occurred in all pea cultivars, the response of salt-tolerant and salt-sensitive cultivars with respect to the generation of enzymatic and non-enzymatic metabolites measured in the present study was not consistent. Of different antioxidant enzymes and metabolites analyzed, only CAT activity was found to be a reliable marker of salt tolerance in the set of pea cultivars examined.

  17. Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli

    Science.gov (United States)

    Wells, Jack A.; Shibata, Sayaka; Fujikawa, Akihiko; Takahashi, Masayasu; Saga, Tsuneo; Aoki, Ichio

    2017-01-01

    Functional neuroimaging, applied to pre-clinical models of chronic pain, offers unique advantages in the drive to discover new treatments for this prevalent and oppressive condition. The high spatial and temporal resolution of fMRI affords detailed mapping of regional pharmacodynamics that underlie mechanisms of pain suppression by new analgesics. Despite evidence supporting the translational relevance of this approach, relatively few studies have investigated fMRI abnormalities in rodent models of chronic pain. In this study, we used fMRI to map the BOLD response in a recently developed putative rat model of fibromyalgia to innocuous and acute nociceptive stimuli by applying a step-wise graded electrical forepaw stimulation paradigm, with comparison to healthy controls. We observed discriminatory functional signatures (p < 0.001) to 2 mA electrical forepaw stimulation, found to be innocuous in the control group. As such, this translational approach provides sensitive and quantitative neural correlates of the underlying chronic disease. The regional patterns of functional augmentation were found to be concordant with previous studies of nociception in the anaesthetised rat brain, supporting the specificity of this approach in the study of altered central pain processing in reserpine induced myalgia. The methodology introduced in this work represents a novel platform for emerging treatment evaluation in highly experimentally controlled conditions. PMID:28079057

  18. Function-Biased Choice of Additives for Optimization of Protein Crystallization: The Case of the Putative Thioesterase PA5185 from Pseudomonas aeruginosa PAO1

    Energy Technology Data Exchange (ETDEWEB)

    Chruszcz, Maksymilian; Zimmerman, Matthew D.; Wang, Shuren; Koclega, Katarzyna D.; Zheng, Heping; Evdokimova, Elena; Kudritska, Marina; Cymborowski, Marcin; Savchenko, Alexei; Edwards, Aled; Minor, Wladek (Toronto); (UV)

    2009-09-15

    The crystal structure of PA5185, a putative thioesterase from Pseudomonas aeruginosa strain PAO1, was solved using multi-wavelength anomalous diffraction to 2.4 {angstrom}. Analysis of the structure and information about the putative function of the protein were used to optimize crystallization conditions. The crystal growth was optimized by applying additives with chemical similarity to a fragment of a putative PA5185 substrate (CoA or its derivative). Using new crystallization conditions containing this function-biased set of additives, several new crystal forms were produced, and structures of three of them (in three different space groups) were determined. One of the new crystal forms had an improved resolution limit of 1.9 {angstrom}, and another displayed an alternative conformation of the highly conserved loop containing Asn26, which could play a physiological role. Surprisingly, none of the additives were ordered in the crystal structures. Application of function-biased additives could be used as a standard optimization protocol for producing improved diffraction, or new crystal forms, which may lead to better understanding of the biological functions of proteins.

  19. Alcohol consumption, cardiovascular health, and endothelial function markers.

    Science.gov (United States)

    Bau, Paulo F D; Bau, Claiton H D; Rosito, Guido A; Manfroi, Waldomiro C; Fuchs, Flávio D

    2007-11-01

    Cardiovascular diseases are among the worldwide leading causes of shorter life expectancy and loss of quality of life. Thus, any influence of diet or life habits on the cardiovascular system may have important implications for public health. Most world populations consume alcoholic beverages. Since alcohol may have both protective and harmful effects on cardiovascular health, the identification of biochemical mechanisms that could explain such paradoxical effects is warranted. The vascular endothelium is the target of important mediating pathways of differential ethanol concentrations, such as oxidative stress, lipoproteins, and insulin resistance. Alcohol-induced endothelial damage or protection may be related to the synthesis or action of several markers, such as nitric oxide, cortisol, endothelin-1, adhesion molecules, tumor necrosis factor alpha, interleukin-6, C-reactive protein, and haemostatic factors. The expression of these markers is consistent with the J-shaped curve between alcohol consumption and cardiovascular health. However, there is genetic and phenotypic heterogeneity in alcohol response, and despite the apparent beneficial biochemical effects of low doses of ethanol, there is not enough clinical and epidemiological evidence to allow the recommendation to consume alcoholic beverages for abstemious individuals. Considering the potential for addiction of alcoholic beverage consumption and other negative consequences of alcohol, it would be worthwhile to identify substances able to mimic the beneficial effects of low doses of ethanol without its adverse effects.

  20. Putative Markers of Adulteration of Higher-Grade Olive Oil with Less Expensive Pomace Olive Oil Identified by Gas Chromatography Combined with Chemometrics.

    Science.gov (United States)

    Jabeur, Hazem; Drira, Malika; Rebai, Ahmed; Bouaziz, Mohamed

    2017-07-05

    This work has been performed to ascertain that extra-virgin olive oil (EVOO) is free of adulteration. For this purpose, refined pomace olive oils (RPOOs) are commonly used for extra-virgin olive oil adulteration and repassed olive oils (ROOs) are used for lampante olive oil (LOO) fraudulent operation. Indeed, fatty acid ethyl esters could be used as a parameter for the detection of EVOO fraud with 2% RPOO. The addition of >10% RPOO to EVOO would be detected by the amount of erythrodiol, uvaol, waxes, and aliphatic alcohols. Moreover, the use of stigmasta-3,5-diene content proved to be effective in EVOO adulteration even at a low level (with 1% RPOO). For the detection of adulteration of LOO with >5% ROO, the sum of erythrodiol, uvaol, and the waxes and esters can be considered as good markers of purity. Using linear discriminant analysis can identify the most discriminant variable that allows a faster and cheaper evaluation of extra-virgin olive oil adulteration by measuring only these variables.

  1. Genetic mapping reveals that sinefungin resistance in Toxoplasma gondii is controlled by a putative amino acid transporter locus that can be used as a negative selectable marker.

    Science.gov (United States)

    Behnke, Michael S; Khan, Asis; Sibley, L David

    2015-02-01

    Quantitative trait locus (QTL) mapping studies have been integral in identifying and understanding virulence mechanisms in the parasite Toxoplasma gondii. In this study, we interrogated a different phenotype by mapping sinefungin (SNF) resistance in the genetic cross between type 2 ME49-FUDR(r) and type 10 VAND-SNF(r). The genetic map of this cross was generated by whole-genome sequencing of the progeny and subsequent identification of single nucleotide polymorphisms (SNPs) inherited from the parents. Based on this high-density genetic map, we were able to pinpoint the sinefungin resistance phenotype to one significant locus on chromosome IX. Within this locus, a single nonsynonymous SNP (nsSNP) resulting in an early stop codon in the TGVAND_290860 gene was identified, occurring only in the sinefungin-resistant progeny. Using CRISPR/CAS9, we were able to confirm that targeted disruption of TGVAND_290860 renders parasites sinefungin resistant. Because disruption of the SNR1 gene confers resistance, we also show that it can be used as a negative selectable marker to insert either a positive drug selection cassette or a heterologous reporter. These data demonstrate the power of combining classical genetic mapping, whole-genome sequencing, and CRISPR-mediated gene disruption for combined forward and reverse genetic strategies in T. gondii.

  2. Ribosomal genes and heat shock proteins as putative markers for chronic, sublethal heat stress in Arctic charr: applications for aquaculture and wild fish.

    Science.gov (United States)

    Quinn, Nicole L; McGowan, Colin R; Cooper, Glenn A; Koop, Ben F; Davidson, William S

    2011-09-22

    Arctic charr thrive at high densities and can live in freshwater year round, making this species especially suitable for inland, closed containment aquaculture. However, it is a cold-water salmonid, which both limits where the species can be farmed and places wild populations at particular risk to climate change. Previously, we identified genes associated with tolerance and intolerance to acute, lethal temperature stress in Arctic charr. However, there remained a need to examine the genes involved in the stress response to more realistic temperatures that could be experienced during a summer heat wave in grow-out tanks that are not artificially cooled, or under natural conditions. Here, we exposed Arctic charr to sublethal heat stress of 15-18°C for 72 h, and gill tissues extracted before, during (i.e., at 72 h), immediately after cooling and after 72 h of recovery at ambient temperature (6°C) were used for gene expression profiling by microarray and qPCR analyses. The results revealed an expected pattern for heat shock protein expression, which was highest during heat exposure, with significantly reduced expression (approaching control levels) quickly thereafter. We also found that the expression of numerous ribosomal proteins was significantly elevated immediately and 72 h after cooling, suggesting that the gill tissues were undergoing ribosome biogenesis while recovering from damage caused by heat stress. We suggest that these are candidate gene targets for the future development of genetic markers for broodstock development or for monitoring temperature stress and recovery in wild or cultured conditions.

  3. Functional measures, inflammatory markers and endothelin-1 as predictors of 360-day survival in centenarians

    OpenAIRE

    Szewieczek, Jan; Francuz, Tomasz; Dulawa, Jan; Legierska, Katarzyna; Hornik, Beata; W?odarczyk, Iwona; Janusz-Jencze?, Magdalena; Batko-Szwaczka, Agnieszka

    2015-01-01

    Centenarians represent a rapidly growing population. To better characterize this specific age group, we have performed a cross-sectional study to observe associations between functional measures and a range of biochemical markers, including inflammatory markers and their significance as predictors of 360-day survival. Medical history and physical and functional assessment (Mini-Mental State Examination (MMSE), Katz Index (activities of daily living, ADL) and Barthel Index (Barthel Index) of A...

  4. Short communication. An improved intersubspecific genetic map in Lens including functional markers

    Directory of Open Access Journals (Sweden)

    R. de la Puente

    2012-12-01

    Full Text Available A previous Lens genetic map was improved by adding 31 molecular genetic markers, reaching a total of 190 markers with undistorted segregation. Data were obtained from the segregational analysis of 113 F2 plants generated from a single hybrid of Lens culinaris ssp. culinaris × L. c. ssp. orientalis. The added markers are predominantly codominant (15 SSRs, five CAPSs, four presence-absence polymorphisms, three length polymorphisms, two RAPDs, and two SRAPs. At a LOD score of 3.0, the 190 markers were grouped into eight linkage groups (LG covering 2,234.4 cM, with an average distance between markers of 12.28 cM. This linkage map has reduced the numbers of linkage groups from ten in the previous map to eight. Most of the added markers must be functional markers since primers were mostly designed to amplify transcribed sequences. Some of the amplicons were sequenced to test if they were functional markers. One of the sequences showed homology with the Pisum TFL1a gene, involved in the transition from vegetative to flowering stages. This lentil gene was located in the LG 1 thanks to the presence of a polymorphic microsatellite in the first intron of the gene. Since L. culinaris ssp. orientalis is the primary source of additional genetic variability for lentil, this improved map could help in the use of such variability in lentil breeding programs.

  5. Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

    Science.gov (United States)

    Puvanenthiran, Soozana; Essapen, Sharadah; Seddon, Alan M.; Modjtahedi, Helmout

    2016-01-01

    Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 μM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2

  6. Functional Characterization of PaLAX1, a Putative Auxin Permease, in Heterologous Plant Systems1[W][OA

    Science.gov (United States)

    Hoyerová, Klára; Perry, Lucie; Hand, Paul; Laňková, Martina; Kocábek, Tomáš; May, Sean; Kottová, Jana; Pačes, Jan; Napier, Richard; Zažímalová, Eva

    2008-01-01

    We have isolated the cDNA of the gene PaLAX1 from a wild cherry tree (Prunus avium). The gene and its product are highly similar in sequences to both the cDNAs and the corresponding protein products of AUX/LAX-type genes, coding for putative auxin influx carriers. We have prepared and characterized transformed Nicotiana tabacum and Arabidopsis thaliana plants carrying the gene PaLAX1. We have proved that constitutive overexpression of PaLAX1 is accompanied by changes in the content and distribution of free indole-3-acetic acid, the major endogenous auxin. The increase in free indole-3-acetic acid content in transgenic plants resulted in various phenotype changes, typical for the auxin-overproducing plants. The uptake of synthetic auxin, 2,4-dichlorophenoxyacetic acid, was 3 times higher in transgenic lines compared to the wild-type lines and the treatment with the auxin uptake inhibitor 1-naphthoxyacetic acid reverted the changes caused by the expression of PaLAX1. Moreover, the agravitropic response could be restored by expression of PaLAX1 in the mutant aux1 plants, which are deficient in auxin influx carrier activity. Based on our data, we have concluded that the product of the gene PaLAX1 promotes the uptake of auxin into cells, and, as a putative auxin influx carrier, it affects the content and distribution of free endogenous auxin in transgenic plants. PMID:18184737

  7. FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Giulia Gentile

    2016-11-01

    Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

  8. Fluorescently labeled cyclodextrin derivatives as exogenous markers for real-time transcutaneous measurement of renal function

    NARCIS (Netherlands)

    Huang, Jiaguo; Weinfurter, Stefanie; Pinto, Pedro Caetano; Pretze, Marc; Kränzlin, Bettina; Pill, Johannes; Federica, Rodeghiero; Perciaccante, Rossana; Ciana, Leopoldo Della; Masereeuw, Rosalinde; Gretz, Norbert

    2016-01-01

    Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal

  9. Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function

    NARCIS (Netherlands)

    Huang, J.; Weinfurter, S.; Pinto, P.C.; Pretze, M.; Kranzlin, B.; Pill, J.; Federica, R.; Perciaccante, R.; Ciana, L.D.; Masereeuw, R.; Gretz, N.

    2016-01-01

    Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPbetaCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPbetaCD was designed based on the principle of renal

  10. Methanol clusters (CH3OH)n: putative global minimum-energy structures from model potentials and dispersion-corrected density functional theory.

    Science.gov (United States)

    Kazachenko, Sergey; Bulusu, Satya; Thakkar, Ajit J

    2013-06-14

    Putative global minima are reported for methanol clusters (CH3OH)n with n ≤ 15. The predictions are based on global optimization of three intermolecular potential energy models followed by local optimization and single-point energy calculations using two variants of dispersion-corrected density functional theory. Recurring structural motifs include folded and/or twisted rings, folded rings with a short branch, and stacked rings. Many of the larger structures are stabilized by weak C-H···O bonds.

  11. [Development and appraisement of functional molecular marker: intron sequence amplified polymorphism (ISAP)].

    Science.gov (United States)

    Lu, Cai-Rui; Yu, Shu-Xun; Yu, Ji-Wen; Fan, Shu-Li; Song, Mei-Zhen; Wang, Wu; Ma, Shu-Juan

    2008-09-01

    Molecular markers are playing an increasingly important role in map construction, QTL analysis, gene mapping and marker-assisted selection. Researchers hope the target gene and locus are as close as possible, one locus can present one gene, or linked with some important trait, then, individuals with useful trait can be selected through molecular markers selecting, and it's the functional molecular marker. PCR-based molecular markers such as RAPD, SSR, AFLP amplified non-coding regions, or the whole genome randomly, the locus is far away from the gene of targeted trait, this limit the ap-plication of these molecular markers. This study established a kind of functional molecular markers based on intron of gene sequence, trying to link loci with gene sequence to achieve the purpose of its function. It used the conservative consistent sequence of intron splicing sites as its core sequence of amplification. ISAP is a PCR-based marker system, it has two kinds of primers: forward primer and reverse primer, both primers are 18 bases. Any of the primers can be used to construct a primer combination with the other kind of primers. Seventeen primers, 9 forward and 8 reverse, were used to construct 72 primer combinations, 67 of them showed polymorphism in a G. hirsutum cv. CCRI36 x G. barbadense cv. H7124 F2 population and a total of 212 loci were obtained. Together with 164 SRAP loci, these 212 loci were used to construct a genetic linkage map. ISAP markers distributed evenly in the entire linkage group, part of the region had a high saturation, might be the coding sequence-rich region. Sequencing results of 20 fragments showed that 85% of the sequences announced homology with published EST sequence stored in the NCBI which indicated that they were amplified adjacent to expressed sequences. These results showed that ISAP marker system was simple, efficient, reliable, and had a relatively high polymorphism, furthermore, it directly targeted gene sequence, was a functional

  12. Evaluation of the effect of wheat aleurone-rich foods on markers of antioxidant status, inflammation and endothelial function in apparently healthy men and women.

    Science.gov (United States)

    Price, Ruth K; Wallace, Julie M W; Hamill, Lesley L; Keaveney, Edel M; Strain, J J; Parker, Michael J; Welch, Robert W

    2012-11-14

    Observational data show an inverse association between the consumption of whole-grain foods, and inflammation and related diseases. Although the underlying mechanisms are unclear, whole grains, and in particular the aleurone layer, contain a wide range of components with putative antioxidant and anti-inflammatory effects. We evaluated the effects of a diet high in wheat aleurone on plasma antioxidants status, markers of inflammation and endothelial function. In this parallel, participant-blinded intervention, seventy-nine healthy, older, overweight participants (45-65 years, BMI>25 kg/m²) incorporated either aleurone-rich cereal products (27 g aleurone/d), or control products balanced for fibre and macronutrients, into their habitual diets for 4 weeks. Fasting blood samples were taken at baseline and on day 29. Results showed that, compared to control, consumption of aleurone-rich products provided substantial amounts of micronutrients and phytochemicals which may function as antioxidants. Additionally, incorporating these products into a habitual diet resulted in significantly lower plasma concentrations of the inflammatory marker, C-reactive protein (P = 0·035), which is an independent risk factor for CVD. However, no changes were observed in other markers of inflammation, antioxidant status or endothelial function. These results provide a possible mechanism underlying the beneficial effects of longer-term whole-grain intake. However, it is unclear whether this effect is owing to a specific component, or a combination of components in wheat aleurone.

  13. Mild Cognitive Impairment is Associated with Selected Functional Markers: Integrating Concurrent, Longitudinal, and Stability Effects

    Science.gov (United States)

    Dolcos, Sanda; MacDonald, Stuart W.S.; Braslavsky, Anna; Camicioli, Richard; Dixon, Roger A.

    2013-01-01

    Objective We examined functional performance on multiple indicators for two cognitive status groups: (a) not impaired controls (NIC) and (b) mild cognitive impairment (MCI). We identified functional markers associated with differences, changes, and stability in cognitive status. Method In the Victoria Longitudinal Study (VLS) we examined cognitive status group effects in (a) cross-sectional functional performance, (b) longitudinal stability, (c) longitudinal functional performance change, and (d) functional marker prediction of later cognitive status. We assembled markers from five continuous clusters of MCI-related functional factors: biological vitality, activity lifestyle, psychosocial affect, subjective health, and global cognition. We used a cross-sectional sample and a two-wave longitudinal sample, stratified by age (mid-old, old-old) and cognitive status (MCI, NIC). Results First, cross-sectional results showed that eight markers differentiated MCI and NIC adults, with the latter performing uniformly better. The groups differed on diastolic blood pressure, body mass index, positive and negative affect, MMSE, and the lifestyle indicators of self-maintenance, travel, and novel cognitive activities. Second, Wave1 to Wave2 stabilities in cognitive status classification were high. Third, several markers differentiated the stable (NIC-to-NIC, MCI-to-MCI) from the unstable (NIC-to-MCI, MCI-to-NIC) cognitive status groups. Fourth, five relevant markers for identifying older adults at risk for cognitive status changes were: diastolic blood pressure, self-maintenance activities, novel cognitive activities, positive affect, and global cognitive status. Conclusion Selected risk and protective factors differentiate persons classified with MCI from those not currently cognitively impaired, both cross-sectionally and longitudinally. PMID:22251311

  14. Genome-wide transcriptome analysis of the plant pathogen Xanthomonas identifies sRNAs with putative virulence functions

    Science.gov (United States)

    Schmidtke, Cornelius; Findeiß, Sven; Sharma, Cynthia M.; Kuhfuß, Juliane; Hoffmann, Steve; Vogel, Jörg; Stadler, Peter F.; Bonas, Ulla

    2012-01-01

    The Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) is an important model to elucidate the mechanisms involved in the interaction with the host. To gain insight into the transcriptome of the Xcv strain 85–10, we took a differential RNA sequencing (dRNA-seq) approach. Using a novel method to automatically generate comprehensive transcription start site (TSS) maps we report 1421 putative TSSs in the Xcv genome. Genes in Xcv exhibit a poorly conserved −10 promoter element and no consensus Shine-Dalgarno sequence. Moreover, 14% of all mRNAs are leaderless and 13% of them have unusually long 5′-UTRs. Northern blot analyses confirmed 16 intergenic small RNAs and seven cis-encoded antisense RNAs in Xcv. Expression of eight intergenic transcripts was controlled by HrpG and HrpX, key regulators of the Xcv type III secretion system. More detailed characterization identified sX12 as a small RNA that controls virulence of Xcv by affecting the interaction of the pathogen and its host plants. The transcriptional landscape of Xcv is unexpectedly complex, featuring abundant antisense transcripts, alternative TSSs and clade-specific small RNAs. PMID:22080557

  15. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  16. Functional marker development is challenged by the ubiquity of endophytes-a practical perspective.

    Science.gov (United States)

    Arnholdt-Schmitt, Birgit; Valadas, Vera; Döring, Matthias

    2016-01-01

    Functional markers (FMs) are supposed to assist in diagnosis, disease treatment and turning plant and animal breeding more efficient. However, efficient FM application is challenged through current insights in the multi-organism nature of life. This letter aims to raise awareness for re-thinking concepts for FM development in plant breeding and proposes a novel perspective.

  17. Determinants of DHA status and functional effects on metabolic markers and immune modulation in early life

    DEFF Research Database (Denmark)

    Harsløf, Laurine Bente Schram

    by identifying the involved pathways and genes. The second part of the PhD thesis explores whether functional effects of n-3 LCPUFA on metabolic markers and immune maturation in young children can be supported by polymorphisms in genes involved in the mechanisms (PPARG2, COX2 and NFKB1). Results can be found...

  18. Molecular and functional characterization of cDNAs putatively encoding carboxylesterases from the migratory locust, Locusta migratoria.

    Directory of Open Access Journals (Sweden)

    Jianqin Zhang

    Full Text Available Carboxylesterases (CarEs belong to a superfamily of metabolic enzymes encoded by a number of genes and are widely distributed in microbes, plants and animals including insects. These enzymes play important roles in detoxification of insecticides and other xenobiotics, degradation of pheromones, regulation of neurodevelopment, and control of animal development. In this study, we characterized a total of 39 full-length cDNAs putatively encoding different CarEs from the migratory locust, Locusta migratoria, one of the most severe insect pests in many regions of the world, and evaluated the role of four CarE genes in insecticide detoxification. Our phylogenetic analysis grouped the 39 CarEs into five different clades including 20 CarEs in clade A, 3 in D, 13 in E, 1 in F and 2 in I. Four CarE genes (LmCesA3, LmCesA20, LmCesD1, LmCesE1, representing three different clades (A, D and E, were selected for further analyses. The transcripts of the four genes were detectable in all the developmental stages and tissues examined. LmCesA3 and LmCesE1 were mainly expressed in the fat bodies and Malpighian tubules, whereas LmCesA20 and LmCesD1 were predominately expressed in the muscles and hemolymph, respectively. The injection of double-stranded RNA (dsRNA synthesized from each of the four CarE genes followed by the bioassay with each of four insecticides (chlorpyrifos, malathion, carbaryl and deltamethrin increased the nymphal mortalities by 37.2 and 28.4% in response to malathion after LmCesA20 and LmCesE1 were silenced, respectively. Thus, we proposed that both LmCesA20 and LmCesE1 played an important role in detoxification of malathion in the locust. These results are expected to help researchers reveal the characteristics of diverse CarEs and assess the risk of insecticide resistance conferred by CarEs in the locust and other insect species.

  19. Molecular and functional characterization of cDNAs putatively encoding carboxylesterases from the migratory locust, Locusta migratoria.

    Science.gov (United States)

    Zhang, Jianqin; Li, Daqi; Ge, Pingting; Guo, Yaping; Zhu, Kun Yan; Ma, Enbo; Zhang, Jianzhen

    2014-01-01

    Carboxylesterases (CarEs) belong to a superfamily of metabolic enzymes encoded by a number of genes and are widely distributed in microbes, plants and animals including insects. These enzymes play important roles in detoxification of insecticides and other xenobiotics, degradation of pheromones, regulation of neurodevelopment, and control of animal development. In this study, we characterized a total of 39 full-length cDNAs putatively encoding different CarEs from the migratory locust, Locusta migratoria, one of the most severe insect pests in many regions of the world, and evaluated the role of four CarE genes in insecticide detoxification. Our phylogenetic analysis grouped the 39 CarEs into five different clades including 20 CarEs in clade A, 3 in D, 13 in E, 1 in F and 2 in I. Four CarE genes (LmCesA3, LmCesA20, LmCesD1, LmCesE1), representing three different clades (A, D and E), were selected for further analyses. The transcripts of the four genes were detectable in all the developmental stages and tissues examined. LmCesA3 and LmCesE1 were mainly expressed in the fat bodies and Malpighian tubules, whereas LmCesA20 and LmCesD1 were predominately expressed in the muscles and hemolymph, respectively. The injection of double-stranded RNA (dsRNA) synthesized from each of the four CarE genes followed by the bioassay with each of four insecticides (chlorpyrifos, malathion, carbaryl and deltamethrin) increased the nymphal mortalities by 37.2 and 28.4% in response to malathion after LmCesA20 and LmCesE1 were silenced, respectively. Thus, we proposed that both LmCesA20 and LmCesE1 played an important role in detoxification of malathion in the locust. These results are expected to help researchers reveal the characteristics of diverse CarEs and assess the risk of insecticide resistance conferred by CarEs in the locust and other insect species.

  20. Structural equation modeling identifies markers of damage and function in the aging male Fischer 344 rat.

    Science.gov (United States)

    Grunz-Borgmann, Elizabeth A; Nichols, LaNita A; Wiedmeyer, Charles E; Spagnoli, Sean; Trzeciakowski, Jerome P; Parrish, Alan R

    2016-06-01

    The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, elevations in the more sensitive markers of function, plasma cystatin C and proteinuria, were detectable at 16 and 18 months, respectively. Interestingly, cystatin C levels were not corrected by caloric restriction. Urinary Kim-1, a marker of CKD, was elevated as early as 16 months. Klotho gene expression was significantly decreased at 24 months, but not at earlier timepoints. Alterations in renal structure, glomerulosclerosis and tubulointerstitial fibrosis, were noted at 16 months, with little change from 18 to 24 months. Tubulointerstitial inflammation was increased at 16 months, and remained similar from 18 to 24 months. A SEM (structural equation modeling) model of age-related renal dysfunction suggests that proteinuria is a marker of renal damage, while urinary Kim-1 is a marker of both damage and function. Taken together, these results demonstrate that age-dependent nephropathy begins as early as 16 months and progresses rapidly over the next 8 months.

  1. Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function.

    Science.gov (United States)

    Huang, Jiaguo; Weinfurter, Stefanie; Pinto, Pedro Caetano; Pretze, Marc; Kränzlin, Bettina; Pill, Johannes; Federica, Rodeghiero; Perciaccante, Rossana; Ciana, Leopoldo Della; Masereeuw, Rosalinde; Gretz, Norbert

    2016-10-19

    Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal clearance of designed drugs. It displays favorable fluorescent properties, high hydrophilicity, low plasma protein binding, and high stability in porcine liver esterase as well as in plasma and nontoxicity. More importantly, FITC-HPβCD can be efficiently and rapidly filtered by glomerulus and completely excreted into urine without proximal tubular reabsorption or secretion in rat models. Additionally, the marker was well-tolerated, with nearly 100% urinary recovery of the given doses, and no metabolism were found. Relying on this novel kidney function marker and transcutaneous devices, we demonstrate a rapid, robust, and convenient approach for real-time assessing renal function without the need of time-consuming blood and urine sample preparation. Our work provides a promising tool for noninvasive real-time monitoring of renal function in vivo.

  2. Functional Characterization of a Putative Glycine max ELF4 in Transgenic Arabidopsis and Its Role during Flowering Control

    Directory of Open Access Journals (Sweden)

    Alexandre L. Nepomuceno

    2017-04-01

    Full Text Available Flowering is an important trait in major crops like soybean due to its direct relation to grain production. The circadian clock mediates the perception of seasonal changes in day length and temperature to modulate flowering time. The circadian clock gene EARLY FLOWERING 4 (ELF4 was identified in Arabidopsis thaliana and is believed to play a key role in the integration of photoperiod, circadian regulation, and flowering. The molecular circuitry that comprises the circadian clock and flowering control in soybeans is just beginning to be understood. To date, insufficient information regarding the soybean negative flowering regulators exist, and the biological function of the soybean ELF4 (GmELF4 remains unknown. Here, we investigate the ELF4 family members in soybean and functionally characterize a GmELF4 homologous gene. The constitutive overexpression of GmELF4 delayed flowering in Arabidopsis, showing the ELF4 functional conservation among plants as part of the flowering control machinery. We also show that GmELF4 alters the expression of Arabidopsis key flowering time genes (AtCO and AtFT, and this down-regulation is the likely cause of flowering delay phenotypes. Furthermore, we identified the GmELF4 network genes to infer the participation of GmELF4 in soybeans. The data generated in this study provide original insights for comprehending the role of the soybean circadian clock ELF4 gene as a negative flowering controller.

  3. Effects of reciprocal transplantation on the microbiome and putative nitrogen cycling functions of the intertidal sponge, Hymeniacidon heliophila

    Science.gov (United States)

    Weigel, Brooke L.; Erwin, Patrick M.

    2017-01-01

    Microbial symbionts in sponges are ubiquitous, forming complex and highly diverse host-specific communities. Conspecific sponges display remarkable stability in their symbiont communities, both spatially and temporally, yet extreme fluctuations in environmental factors can cause shifts in host-symbiont associations. We previously demonstrated that the marine sponge Hymeniacidon heliophila displayed significant community-level differences in microbial symbiont diversity, structure and composition when sampled from intertidal and subtidal environments. Here, we conducted a 70-day reciprocal transplant experiment to directly test the effect of tidal exposure on the microbiome of H. heliophila, using next-generation Illumina sequencing of 16S rRNA gene sequences to characterize symbiont communities. While sponges transplanted between habitats displayed shifts in microbial communities after 70 days, temporal variation was the dominant factor affecting microbial community composition. Further, we identified core symbionts that persisted across these spatio-temporal scales and used a metagenomic approach to show that these dominant members of the microbiome of H. heliophila represent nitrogen cycling taxa that have the potential to contribute to a diverse array of nitrogen transformations in the sponge holobiont. Together, these results indicate that despite moderate spatio-temporal shifts in symbiont composition, core symbiont functions (e.g. nitrogen cycling) can be maintained in sponge microbiomes through functional redundancy. PMID:28233813

  4. DISCLOSE : DISsection of CLusters Obtained by SEries of transcriptome data using functional annotations and putative transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Silvis Remko

    2008-12-01

    Full Text Available Abstract Background A typical step in the analysis of gene expression data is the determination of clusters of genes that exhibit similar expression patterns. Researchers are confronted with the seemingly arbitrary choice between numerous algorithms to perform cluster analysis. Results We developed an exploratory application that benchmarks the results of clustering methods using functional annotations. In addition, a de novo DNA motif discovery algorithm is integrated in our program which identifies overrepresented DNA binding sites in the upstream DNA sequences of genes from the clusters that are indicative of sites of transcriptional control. The performance of our program was evaluated by comparing the original results of a time course experiment with the findings of our application. Conclusion DISCLOSE assists researchers in the prokaryotic research community in systematically evaluating results of the application of a range of clustering algorithms to transcriptome data. Different performance measures allow to quickly and comprehensively determine the best suited clustering approach for a given dataset.

  5. Gut microbiomes of free-ranging and captive Namibian cheetahs: Diversity, putative functions and occurrence of potential pathogens.

    Science.gov (United States)

    Wasimuddin; Menke, Sebastian; Melzheimer, Jörg; Thalwitzer, Susanne; Heinrich, Sonja; Wachter, Bettina; Sommer, Simone

    2017-08-07

    Although the significance of the gut microbiome for host health is well acknowledged, the impact of host traits and environmental factors on the interindividual variation of gut microbiomes of wildlife species is not well understood. Such information is essential; however, as changes in the composition of these microbial communities beyond the natural range might cause dysbiosis leading to increased susceptibility to infections. We examined the potential influence of sex, age, genetic relatedness, spatial tactics and the environment on the natural range of the gut microbiome diversity in free-ranging Namibian cheetahs (Acinonyx jubatus). We further explored the impact of an altered diet and frequent contact with roaming dogs and cats on the occurrence of potential bacterial pathogens by comparing free-ranging and captive individuals living under the same climatic conditions. Abundance patterns of particular bacterial genera differed between the sexes, and bacterial diversity and richness were higher in older (>3.5 years) than in younger individuals. In contrast, male spatial tactics, which probably influence host exposure to environmental bacteria, had no discernible effect on the gut microbiome. The profound resemblance of the gut microbiome of kin in contrast to nonkin suggests a predominant role of genetics in shaping bacterial community characteristics and functional similarities. We also detected various Operational Taxonomic Units (OTUs) assigned to potential pathogenic bacteria known to cause diseases in humans and wildlife species, such as Helicobacter spp., and Clostridium perfringens. Captive individuals did not differ in their microbial alpha diversity but exhibited higher abundances of OTUs related to potential pathogenic bacteria and shifts in disease-associated functional pathways. Our study emphasizes the need to integrate ecological, genetic and pathogenic aspects to improve our comprehension of the main drivers of natural variation and shifts in

  6. Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1

    Directory of Open Access Journals (Sweden)

    Suellen D’arc Santos Oliveira

    2014-01-01

    Full Text Available Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca2+ concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca2+ levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression.

  7. A Putative Chloroplast-Localized Ca(2+)/H(+) Antiporter CCHA1 Is Involved in Calcium and pH Homeostasis and Required for PSII Function in Arabidopsis.

    Science.gov (United States)

    Wang, Chao; Xu, Weitao; Jin, Honglei; Zhang, Taijie; Lai, Jianbin; Zhou, Xuan; Zhang, Shengchun; Liu, Shengjie; Duan, Xuewu; Wang, Hongbin; Peng, Changlian; Yang, Chengwei

    2016-08-01

    Calcium is important for chloroplast, not only in its photosynthetic but also nonphotosynthetic functions. Multiple Ca(2+)/H(+) transporters and channels have been described and studied in the plasma membrane and organelle membranes of plant cells; however, the molecular identity and physiological roles of chloroplast Ca(2+)/H(+) antiporters have remained unknown. Here we report the identification and characterization of a member of the UPF0016 family, CCHA1 (a chloroplast-localized potential Ca(2+)/H(+) antiporter), in Arabidopsis thaliana. We observed that the ccha1 mutant plants developed pale green leaves and showed severely stunted growth along with impaired photosystem II (PSII) function. CCHA1 localizes to the chloroplasts, and the levels of the PSII core subunits and the oxygen-evolving complex were significantly decreased in the ccha1 mutants compared with the wild type. In high Ca(2+) concentrations, Arabidopsis CCHA1 partially rescued the growth defect of yeast gdt1Δ null mutant, which is defective in a Ca(2+)/H(+) antiporter. The ccha1 mutant plants also showed significant sensitivity to high concentrations of CaCl2 and MnCl2, as well as variation in pH. Taken these results together, we propose that CCHA1 might encode a putative chloroplast-localized Ca(2+)/H(+) antiporter with critical functions in the regulation of PSII and in chloroplast Ca(2+) and pH homeostasis in Arabidopsis.

  8. Analysis of Two Putative Candida albicans Phosphopantothenoylcysteine Decarboxylase / Protein Phosphatase Z Regulatory Subunits Reveals an Unexpected Distribution of Functional Roles

    Science.gov (United States)

    Petrényi, Katalin; Molero, Cristina; Kónya, Zoltán; Erdődi, Ferenc; Ariño, Joaquin; Dombrádi, Viktor

    2016-01-01

    Protein phosphatase Z (Ppz) is a fungus specific enzyme that regulates cell wall integrity, cation homeostasis and oxidative stress response. Work on Saccharomyces cerevisiae has shown that the enzyme is inhibited by Hal3/Vhs3 moonlighting proteins that together with Cab3 constitute the essential phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. In Candida albicans CaPpz1 is also involved in the morphological changes and infectiveness of this opportunistic human pathogen. To reveal the CaPpz1 regulatory context we searched the C. albicans database and identified two genes that, based on the structure of their S. cerevisiae counterparts, were termed CaHal3 and CaCab3. By pull down analysis and phosphatase assays we demonstrated that both of the bacterially expressed recombinant proteins were able to bind and inhibit CaPpz1 as well as its C-terminal catalytic domain (CaPpz1-Cter) with comparable efficiency. The binding and inhibition were always more pronounced with CaPpz1-Cter, indicating a protective effect against inhibition by the N-terminal domain in the full length protein. The functions of the C. albicans proteins were tested by their overexpression in S. cerevisiae. Contrary to expectations we found that only CaCab3 and not CaHal3 rescued the phenotypic traits that are related to phosphatase inhibition by ScHal3, such as tolerance to LiCl or hygromycin B, requirement for external K+ concentrations, or growth in a MAP kinase deficient slt2 background. On the other hand, both of the Candida proteins turned out to be essential PPCDC components and behaved as their S. cerevisiae counterparts: expression of CaCab3 and CaHal3 rescued the cab3 and hal3 vhs3 S. cerevisiae mutations, respectively. Thus, both CaHal3 and CaCab3 retained the PPCDC related functions and have the potential for CaPpz1 inhibition in vitro. The fact that only CaCab3 exhibits its phosphatase regulatory potential in vivo suggests that in C. albicans CaCab3, but not CaHal3, acts as a

  9. Biochemical analysis of three putative KaiC clock proteins from Synechocystis sp. PCC 6803 suggests their functional divergence.

    Science.gov (United States)

    Wiegard, Anika; Dörrich, Anja K; Deinzer, Hans-Tobias; Beck, Christian; Wilde, Annegret; Holtzendorff, Julia; Axmann, Ilka M

    2013-05-01

    Cyanobacteria have been shown to have a circadian clock system that consists mainly of three protein components: KaiA, KaiB and KaiC. This system is well understood in the cyanobacterium Synechococcus elongatus PCC 7942, for which robust circadian oscillations have been shown. Like many other cyanobacteria, the chromosome of the model cyanobacterium Synechocystis sp. PCC 6803 contains additional kaiC and kaiB gene copies besides the standard kaiABC gene cluster. The respective gene products differ significantly in their amino acid sequences, especially in their C-terminal regions, suggesting different functional characteristics. Here, phosphorylation assays of the three Synechocystis sp. PCC 6803 KaiC proteins revealed that KaiC1 phosphorylation depends on KaiA, as is well documented for the Synechococcus elongatus PCC 7942 KaiC protein, whereas KaiC2 and KaiC3 autophosphorylate independently of KaiA. This was confirmed by in vivo protein-protein interaction studies, which demonstrate that only KaiC1 interacts with KaiA. Furthermore, we demonstrate that the three different Kai proteins form only homomeric complexes in vivo. As only KaiC1 phosphorylation depends on KaiA, a prerequisite for robust oscillations, we suggest that the kaiAB1C1 gene cluster in Synechocystis sp. PCC 6803 controls circadian timing in a manner similar to the clock described in Synechococcus elongatus PCC 7942.

  10. Kinetin Improves Barrier Function of the Skin by Modulating Keratinocyte Differentiation Markers

    Science.gov (United States)

    An, Sungkwan; Cha, Hwa Jun; Ko, Jung-Min; Han, Hyunjoo; Kim, Su Young; Kim, Kyung-Suk; Lee, Song Jeong; An, In-Sook; Kim, Sangwon; Youn, Hae Jeong

    2017-01-01

    Background Kinetin is a plant hormone that regulates growth and differentiation. Keratinocytes, the basic building blocks of the epidermis, function in maintaining the skin barrier. Objective We examined whether kinetin induces skin barrier functions in vitro and in vivo. Methods To evaluate the efficacy of kinetin at the cellular level, expression of keratinocyte differentiation markers was assessed. Moreover, we examined the clinical efficacy of kinetin by evaluating skin moisture, transepidermal water loss (TEWL), and skin surface roughness in patients who used kinetin-containing cream. We performed quantitative real-time polymerase chain reaction to measure the expression of keratinocyte differentiation markers in HaCaT cells following treatment. A clinical trial was performed to assess skin moisture, TEWL, and evenness of skin texture in subjects who used kinetin-containing cream for 4 weeks. Results Kinetin increased involucrin, and keratin 1 mRNA in HaCaT cells. Moreover, use of a kinetin-containing cream improved skin moisture and TEWL while decreasing roughness of skin texture. Conclusion Kinetin induced the expression of keratinocyte differentiation markers, suggesting that it may affect differentiation to improve skin moisture content, TEWL, and other signs of skin aging. Therefore, kinetin is a potential new component for use in cosmetics as an anti-aging agent that improves the barrier function of skin. PMID:28223740

  11. Comprehensive analysis of cystatin family genes suggests their putative functions in sexual reproduction, embryogenesis, and seed formation.

    Science.gov (United States)

    Zhao, Peng; Zhou, Xue-mei; Zou, Jie; Wang, Wei; Wang, Lu; Peng, Xiong-bo; Sun, Meng-xiang

    2014-09-01

    Cystatins are tightly bound and reversible inhibitors of cysteine proteases in C1A and C13 peptidase families, which have been identified in several species and shown to function in vegetative development and response to biotic/abiotic stresses in plants. Recent work revealed their critical role in regulating programmed cell death during embryogenesis in tobacco and suggested their more comprehensive roles in the process of sexual plant reproduction, although little is known about cystatin family genes in the processes. Here, 10 cystatin family genes in Nicotiana tabacum were identified using an expressed sequence tag (EST)-based gene clone strategy. Analysis of their biochemical properties showed that nine of them have the potency to inhibit the activities of both commercial cathepsin L-like proteases and extracted cysteine proteases from seeds, but with different K i values depending on the types of proteases and the developmental stages of the seed tested. This suggests that cystatin-dependent cathepsin L-like proteolytic pathways are probably important for early seed development. Comprehensive expression profile analysis revealed that cystatin family genes showed manifold variations in their transcription levels in different plant cell types, including the sperm, egg, and zygote, especially in the embryo and seed at different developmental stages. More interestingly, intracellular localization analysis of each cystatin revealed that most members of cystatin families are recognized as secretory proteins with signal peptides that direct them to the endoplasmic reticulum. These results suggest their widespread roles in cell fate determination and cell-cell communication in the process of sexual reproduction, especially in gamete and embryo development, as well as in seed formation.

  12. Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response.

    Science.gov (United States)

    Pereira, Andre L A; Carazzolle, Marcelo F; Abe, Valeria Y; de Oliveira, Maria L P; Domingues, Mariane N; Silva, Jaqueline C; Cernadas, Raul A; Benedetti, Celso E

    2014-02-25

    Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. The identification of PthA"s" and PthC"s" targets, such as the LOB (lateral organ boundary) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host

  13. Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

    Science.gov (United States)

    Sangith, Nikhil; Srinivasaraghavan, Kannan; Sahu, Indrajit; Desai, Ankita; Medipally, Spandana; Somavarappu, Arun Kumar; Verma, Chandra; Venkatraman, Prasanna

    2014-01-01

    PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a) proteins with conserved C-termini may share common functions and (b) PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM) at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions. PMID:25009770

  14. Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

    Directory of Open Access Journals (Sweden)

    Nikhil Sangith

    2014-01-01

    Full Text Available PSMD9 (Proteasome Macropain non-ATPase subunit 9, a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a proteins with conserved C-termini may share common functions and (b PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein, S14 (a ribosomal protein, CSH1 (a growth hormone, E12 (a transcription factor and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions.

  15. Genetic diversity of functional food species Spinacia oleracea L. by protein markers.

    Science.gov (United States)

    Rashid, M; Yousaf, Z; Haider, M S; Khalid, S; Rehman, H A; Younas, A; Arif, A

    2014-01-01

    Exploration of genetic diversity contributes primarily towards crop improvement. Spinaciaoleracea L. is a functional food species but unfortunately the genetic diversity of this vegetable is still unexplored. Therefore, this research was planned to explore the genetic diversity of S. oleracea by using morphological and protein markers. Protein profile of 25 accessions was generated on sodium dodecyl sulphate polyacrylamide gel. Total allelic variation of 27 bands was found. Out of these, 20 were polymorphic and the rest of the bands were monomorphic. Molecular weights of the bands ranged from 12.6 to 91.2 kDa. Major genetic differences were observed in accession 20541 (Peshawar) followed by 20180 (Lahore) and 19902 (AVRDC). Significant differences exist in the protein banding pattern. This variation can further be studied by advanced molecular techniques, including two-dimensional electrophoresis and DNA markers.

  16. Determinants of DHA status and functional effects on metabolic markers and immune modulation in early life

    DEFF Research Database (Denmark)

    Harsløf, Laurine Bente Schram

    intake and other potential determinants in infancy and childhood. The first part of the PhD thesis describes several potential determinants of infant and young child DHA status including genetic variation in FADS, breastfeeding and fish intake. Results can be found in Paper 1. Evidence for effects of n-3...... LCPUFA on metabolic markers such as glucose homeostasis, lipid profile and blood pressure in young children is limited. No studies have explored whether polymorphisms of genes encoding proteins involved in the mechanisms behind the effect (such as PPARG2 and COX2) can support the findings of diet studies...... by identifying the involved pathways and genes. The second part of the PhD thesis explores whether functional effects of n-3 LCPUFA on metabolic markers and immune maturation in young children can be supported by polymorphisms in genes involved in the mechanisms (PPARG2, COX2 and NFKB1). Results can be found...

  17. MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function

    Directory of Open Access Journals (Sweden)

    Hofmann Kay

    2002-09-01

    Full Text Available Abstract Background Three macromolecular assemblages, the lid complex of the proteasome, the COP9-Signalosome (CSN and the eIF3 complex, all consist of multiple proteins harboring MPN and PCI domains. Up to now, no specific function for any of these proteins has been defined, nor has the importance of these motifs been elucidated. In particular Rpn11, a lid subunit, serves as the paradigm for MPN-containing proteins as it is highly conserved and important for proteasome function. Results We have identified a sequence motif, termed the MPN+ motif, which is highly conserved in a subset of MPN domain proteins such as Rpn11 and Csn5/Jab1, but is not present outside of this subfamily. The MPN+ motif consists of five polar residues that resemble the active site residues of hydrolytic enzyme classes, particularly that of metalloproteases. By using site-directed mutagenesis, we show that the MPN+ residues are important for the function of Rpn11, while a highly conserved Cys residue outside of the MPN+ motif is not essential. Single amino acid substitutions in MPN+ residues all show similar phenotypes, including slow growth, sensitivity to temperature and amino acid analogs, and general proteasome-dependent proteolysis defects. Conclusions The MPN+ motif is abundant in certain MPN-domain proteins, including newly identified proteins of eukaryotes, bacteria and archaea thought to act outside of the traditional large PCI/MPN complexes. The putative catalytic nature of the MPN+ motif makes it a good candidate for a pivotal enzymatic function, possibly a proteasome-associated deubiquitinating activity and a CSN-associated Nedd8/Rub1-removing activity.

  18. Identification of cold-responsive genes in energycane for their use in genetic diversity analysis and future functional marker development

    Science.gov (United States)

    Breeding for cold tolerance in sugarcane will allow its cultivation as a dedicated biomass crop in cold environments. Development of functional markers to facilitate marker-assisted breeding requires identification of cold stress tolerance genes. Using suppression subtractive hybridization, 465 cold...

  19. Activity-Based Proteomic Profiling of Deubiquitinating Enzymes in Salmonella-Infected Macrophages Leads to Identification of Putative Function of UCH-L5 in Inflammasome Regulation.

    Directory of Open Access Journals (Sweden)

    Evangel Kummari

    Full Text Available Although protein ubiquitination has been shown to regulate multiple processes during host response to Salmonella enterica serovar Typhimurium infection, specific functions of host deubiquitinating enzymes remain unknown in this bacterial infection. By using chemical proteomics approach, in which deubiquitinating enzymes were labeled by an active-site probe and analyzed by quantitative proteomics, we identified novel deubiquitinases in chicken macrophages based on their reactivity with the probe. Also, we detected down-regulation of UCH-L3, and USP4 as well as up-regulation of USP5 and UCH-L5 deubiquitinating enzymes in macrophages infected with Salmonella Typhimurium. We showed that decrease in either UCH-L5 activity, or in UCH-L5 protein amount in chicken and human macrophages infected or stimulated with LPS/nigericin, led to decreased IL-1β release. These data point towards a putative role of UCH-L5 in inflammasome regulation during Salmonella infection. Because inflammasome activation is important in innate resistance to these bacteria, one would expect that naturally occurring or therapeutically induced alteration in UCH-L5 activation would influence disease outcome and could represent a target for new therapeutic approaches.

  20. Activity-Based Proteomic Profiling of Deubiquitinating Enzymes in Salmonella-Infected Macrophages Leads to Identification of Putative Function of UCH-L5 in Inflammasome Regulation.

    Science.gov (United States)

    Kummari, Evangel; Alugubelly, Navatha; Hsu, Chuan-Yu; Dong, Brittany; Nanduri, Bindu; Edelmann, Mariola J

    2015-01-01

    Although protein ubiquitination has been shown to regulate multiple processes during host response to Salmonella enterica serovar Typhimurium infection, specific functions of host deubiquitinating enzymes remain unknown in this bacterial infection. By using chemical proteomics approach, in which deubiquitinating enzymes were labeled by an active-site probe and analyzed by quantitative proteomics, we identified novel deubiquitinases in chicken macrophages based on their reactivity with the probe. Also, we detected down-regulation of UCH-L3, and USP4 as well as up-regulation of USP5 and UCH-L5 deubiquitinating enzymes in macrophages infected with Salmonella Typhimurium. We showed that decrease in either UCH-L5 activity, or in UCH-L5 protein amount in chicken and human macrophages infected or stimulated with LPS/nigericin, led to decreased IL-1β release. These data point towards a putative role of UCH-L5 in inflammasome regulation during Salmonella infection. Because inflammasome activation is important in innate resistance to these bacteria, one would expect that naturally occurring or therapeutically induced alteration in UCH-L5 activation would influence disease outcome and could represent a target for new therapeutic approaches.

  1. Novel loss-of-function putative aminotransferase alleles cause biosynthesis of capsinoids, nonpungent capsaicinoid analogues, in mildly pungent chili peppers (Capsicum chinense).

    Science.gov (United States)

    Tanaka, Yoshiyuki; Hosokawa, Munetaka; Miwa, Tetsuya; Watanabe, Tatsuo; Yazawa, Susumu

    2010-11-24

    Capsinoids are a group of nonpungent capsaicinoid analogues produced in Capsicum fruits. They have similar bioactivities to capsaicinoids such as suppression of fat accumulation and antioxidant activity. They are more palatable ingredients in dietary supplements than capsaicinoids because of their low pungency. Previous studies on nonpungent Capsicum annuum cultivars showed that capsinoid biosynthesis is caused by loss-of-function putative aminotransferase (p-amt) alleles. This study showed that three mildly pungent cultivars of Capsicum chinense (Zavory Hot, Aji Dulce strain 2, and Belize Sweet) contain high levels of capsinoid. It was shown that these cultivars have novel p-amt alleles, which contain mutations that differ from those of C. annuum. Sequence analysis of p-amt in Belize Sweet revealed that a 5 bp insertion (TGGGC) results in a frameshift mutation. A transposable element (Tcc) was found in the p-amt of Zavory Hot and Aji Dulce strain 2. Tcc has features similar to those of the hAT transposon family. This was inserted in the fifth intron of Zavory Hot and in third intron of Aji Dulce strain 2. The p-amt alleles harboring Tcc cannot produce an active p-AMT. These mildly pungent cultivars will provide a new natural source of capsinoids.

  2. SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors.

    Science.gov (United States)

    Oguro, Hideyuki; Ding, Lei; Morrison, Sean J

    2013-07-03

    Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Here we show that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely dividing myeloid-biased HSCs, enabling prospective enrichment of these HSC subsets. Differences in CD229 and CD244 expression resolved CD150(-)CD48(-/low)Lineage(-/low)Sca-1(+)c-Kit(+) cells into a hierarchy of highly purified MPPs that retained erythroid and platelet potential but exhibited progressive changes in mitotic activity and reconstituting potential. Use of these markers, and reconstitution assays, showed that conditional deletion of Scf from endothelial cells and perivascular stromal cells eliminated the vast majority of bone marrow HSCs, including nearly all CD229(-/low) HSCs, demonstrating that quiescent HSCs are maintained by a perivascular niche. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Functional measures, inflammatory markers and endothelin-1 as predictors of 360-day survival in centenarians.

    Science.gov (United States)

    Szewieczek, Jan; Francuz, Tomasz; Dulawa, Jan; Legierska, Katarzyna; Hornik, Beata; Włodarczyk, Iwona; Janusz-Jenczeń, Magdalena; Batko-Szwaczka, Agnieszka

    2015-10-01

    Centenarians represent a rapidly growing population. To better characterize this specific age group, we have performed a cross-sectional study to observe associations between functional measures and a range of biochemical markers, including inflammatory markers and their significance as predictors of 360-day survival. Medical history and physical and functional assessment (Mini-Mental State Examination (MMSE), Katz Index (activities of daily living, ADL) and Barthel Index (Barthel Index) of Activities of Daily Living, and Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)) were conducted on 86 101.9 ± 1.2-year-old (mean ± SD) subjects (70 women, 16 men). Blood tests were performed on 84 subjects of whom 43 also had extended biomarker assessment. As a reference group 30 51.8 ± 5.0-year old healthy subjects (20 women, 10 men) were recruited. The centenarians received follow-up phone calls. Fifty-two centenarians (60 %) survived ≥360 days. Longer survival was associated with higher MMSE (hazard ratio, HR = 0.934, 95 % confidence interval (CI) 0.896-0.975, P = .002), ADL (HR = 0.840, 95 % CI 0.716-0.985, P = .032), Barthel Index (HR = 0.988, 95 % CI 0.977-0.999, P = .026), and albumin level (HR .926, 95 % CI 0.870-0.986, P .016) and with lower white blood cell (WBC) (HR = 1.161, 95 % CI 1.059-1.273, P = .001), C-reactive protein (CRP) (HR = 1.032, 95 % CI 1.014-1.050, P Barthel Index ≥15 (P < .001), Lawton IADL ≥10 points (P = .009), WBC <8.3 G/L (P = .039), CRP <10 mg/L (P < .001), IL-6 <6 pg/mL (P .002), and ET-1 <1.1 pg/mL (P .007). Our results indicate that functional measures, inflammatory markers, and endothelin-1 are predictors of 360-day survival in centenarians.

  4. Heritability of Renal Function and Inflammatory Markers in Adult Male Twins

    Science.gov (United States)

    Raggi, Paolo; Su, Shaoyong; Karohl, Cristina; Veledar, Emir; Rojas-Campos, Enrique; Vaccarino, Viola

    2010-01-01

    Background Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration. PMID:20720405

  5. Molecular Cloning, Functional Characterization and Nutritional Regulation of the Putative Elongase Elovl5 in the Orange-Spotted Grouper (Epinephelus coioides.

    Directory of Open Access Journals (Sweden)

    Songlin Li

    Full Text Available The enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs are widely studied in fish species, as fish are the main source of n-3 LC-PUFAs for human beings. In the present study, a putative gene for elovl5, which encodes a key enzyme involved in LC-PUFA synthesis, was cloned and functionally characterized, and its transcription in response to dietary n-3 LC-PUFA exposure was investigated. Moreover, cell transfection and luciferase assays were used to explore the mechanism underlying the regulation of elovl5. The full-length cDNA of elovl5 was 1242 bp (excluding the polyA tail, including an 885 bp coding region encoding a 295 amino acid protein that possesses all of the characteristic features of elovl proteins. Functional characterization of heterologously expressed grouper Elovl5 indicated that it effectively elongates both C18 (18:2n-6, 18:3n-3, 18:3n-6 and 18:4n-3 and C20 (20:4n-6 and C20:5n-3 PUFAs, but not the C22 substrates. The expression of elovl5 was significantly affected by dietary n-3 LC-PUFA exposure: a high n-3 LC-PUFA level repressed the expression of elovl5 by slightly down-regulating the expression of sterol regulatory element-binding protein (SREBP-1 and liver X receptor (LXR α, which are major regulators of hepatic lipid metabolism. Promoter studies showed that grouper elovl5 reporter activity was induced by over-expression of LXRα but not SREBP-1. This finding suggests that elovl5 is a direct target of LXRα, which is involved in the biosynthesis of PUFAs via transcriptional regulation of elovl5. These findings may contribute to a further understanding of the mechanism underlying the regulation of LC-PUFA biosynthesis in marine fish species.

  6. Molecular Cloning, Functional Characterization and Nutritional Regulation of the Putative Elongase Elovl5 in the Orange-Spotted Grouper (Epinephelus coioides).

    Science.gov (United States)

    Li, Songlin; Yuan, Yuhui; Wang, Tianjiao; Xu, Wei; Li, Mingzhu; Mai, Kangsen; Ai, Qinghui

    2016-01-01

    The enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) are widely studied in fish species, as fish are the main source of n-3 LC-PUFAs for human beings. In the present study, a putative gene for elovl5, which encodes a key enzyme involved in LC-PUFA synthesis, was cloned and functionally characterized, and its transcription in response to dietary n-3 LC-PUFA exposure was investigated. Moreover, cell transfection and luciferase assays were used to explore the mechanism underlying the regulation of elovl5. The full-length cDNA of elovl5 was 1242 bp (excluding the polyA tail), including an 885 bp coding region encoding a 295 amino acid protein that possesses all of the characteristic features of elovl proteins. Functional characterization of heterologously expressed grouper Elovl5 indicated that it effectively elongates both C18 (18:2n-6, 18:3n-3, 18:3n-6 and 18:4n-3) and C20 (20:4n-6 and C20:5n-3) PUFAs, but not the C22 substrates. The expression of elovl5 was significantly affected by dietary n-3 LC-PUFA exposure: a high n-3 LC-PUFA level repressed the expression of elovl5 by slightly down-regulating the expression of sterol regulatory element-binding protein (SREBP)-1 and liver X receptor (LXR) α, which are major regulators of hepatic lipid metabolism. Promoter studies showed that grouper elovl5 reporter activity was induced by over-expression of LXRα but not SREBP-1. This finding suggests that elovl5 is a direct target of LXRα, which is involved in the biosynthesis of PUFAs via transcriptional regulation of elovl5. These findings may contribute to a further understanding of the mechanism underlying the regulation of LC-PUFA biosynthesis in marine fish species.

  7. Marker2sequence, mine your QTL regions for candidate genes

    NARCIS (Netherlands)

    Chibon, P.Y.F.R.P.; Schoof, H.; Visser, R.G.F.; Finkers, H.J.

    2012-01-01

    Marker2sequence (M2S) aims at mining quantitative trait loci (QTLs) for candidate genes. For each gene, within the QTL region, M2S uses data integration technology to integrate putative gene function with associated gene ontology terms, proteins, pathways and literature. As a typical QTL region

  8. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

    Science.gov (United States)

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Kuchenbaecker, Karoline B; Droit, Arnaud; Michailidou, Kyriaki; Ghoussaini, Maya; Kar, Siddhartha; Freeman, Adam; Hopper, John L; Milne, Roger L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Agata, Simona; Ahmed, Shahana; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arason, Adalgeir; Arndt, Volker; Arun, Banu K; Arver, Brita; Bacot, Francois; Barrowdale, Daniel; Baynes, Caroline; Beeghly-Fadiel, Alicia; Benitez, Javier; Bermisheva, Marina; Blomqvist, Carl; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Carpenter, Jane; Chang-Claude, Jenny; Choi, Ji-Yeob; Claes, Kathleen B M; Clarke, Christine; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; de la Hoya, Miguel; De Leeneer, Kim; Devilee, Peter; Diez, Orland; Domchek, Susan M; Doody, Michele; Dorfling, Cecilia M; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Dwek, Miriam; Dworniczak, Bernd; Egan, Kathleen; Eilber, Ursula; Einbeigi, Zakaria; Ejlertsen, Bent; Ellis, Steve; Frost, Debra; Lalloo, Fiona; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Friedlander, Michael; Friedman, Eitan; Gambino, Gaetana; Gao, Yu-Tang; Garber, Judy; García-Closas, Montserrat; Gehrig, Andrea; Damiola, Francesca; Lesueur, Fabienne; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Giles, Graham G; Godwin, Andrew K; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hartikainen, Jaana M; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Hogervorst, Frans B L; Verhoef, Senno; Hendricks, Carolyn B; Hillemanns, Peter; Hollestelle, Antoinette; Hulick, Peter J; Hunter, David J; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Joly Beauparlant, Charles; Jones, Michael; Kabisch, Maria; Kang, Daehee; Karlan, Beth Y; Kauppila, Saila; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Knight, Julia A; Konstantopoulou, Irene; Kraft, Peter; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Le Marchand, Loic; Lee, Chuen Neng; Lee, Min Hyuk; Lester, Jenny; Li, Jingmei; Liljegren, Annelie; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mai, Phuong L; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McGuffog, Lesley; Meindl, Alfons; Menegaux, Florence; Montagna, Marco; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Newcomb, Polly A; Nord, Silje; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olswold, Curtis; Osorio, Ana; Papi, Laura; Park-Simon, Tjoung-Won; Paulsson-Karlsson, Ylva; Peeters, Stephanie; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Pfeiler, Georg; Phelan, Catherine M; Presneau, Nadege; Radice, Paolo; Rahman, Nazneen; Ramus, Susan J; Rashid, Muhammad Usman; Rennert, Gad; Rhiem, Kerstin; Rudolph, Anja; Salani, Ritu; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Schoemaker, Minouk J; Schürmann, Peter; Seynaeve, Caroline; Shen, Chen-Yang; Shrubsole, Martha J; Shu, Xiao-Ou; Sigurdson, Alice; Singer, Christian F; Slager, Susan; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Swerdlow, Anthony; Szabo, Csilla I; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Mary Beth; Tessier, Daniel C; Teulé, Alex; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda E; Tung, Nadine; Turnbull, Clare; van den Ouweland, Ans M W; van Rensburg, Elizabeth J; Ven den Berg, David; Vijai, Joseph; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Whittemore, Alice S; Winqvist, Robert; Wong, Tien Y; Wu, Anna H; Yannoukakos, Drakoulis; Yu, Jyh-Cherng; Pharoah, Paul D P; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison M; Simard, Jacques; Couch, Fergus J; Antoniou, Antonis C; Easton, Douglas F; Zheng, Wei

    2016-06-21

    Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby

  9. Establishment of Relational Model of Congenital Heart Disease Markers and GO Functional Analysis of the Association between Its Serum Markers and Susceptibility Genes

    Directory of Open Access Journals (Sweden)

    Min Liu

    2016-01-01

    Full Text Available Purpose. The purpose of present study was to construct the best screening model of congenital heart disease serum markers and to provide reference for further prevention and treatment of the disease. Methods. Documents from 2006 to 2014 were collected and meta-analysis was used for screening susceptibility genes and serum markers closely related to the diagnosis of congenital heart disease. Data of serum markers were extracted from 80 congenital heart disease patients and 80 healthy controls, respectively, and then logistic regression analysis and support vector machine were utilized to establish prediction models of serum markers and Gene Ontology (GO functional annotation. Results. Results showed that NKX2.5, GATA4, and FOG2 were susceptibility genes of congenital heart disease. CRP, BNP, and cTnI were risk factors of congenital heart disease (p<0.05; cTnI, hs-CRP, BNP, and Lp(a were significantly close to congenital heart disease (p<0.01. ROC curve indicated that the accuracy rate of Lp(a and cTnI, Lp(a and BNP, and BNP and cTnI joint prediction was 93.4%, 87.1%, and 97.2%, respectively. But the detection accuracy rate of the markers’ relational model established by support vector machine was only 85%. GO analysis suggested that NKX2.5, GATA4, and FOG2 were functionally related to Lp(a and BNP. Conclusions. The combined markers model of BNP and cTnI had the highest accuracy rate, providing a theoretical basis for the diagnosis of congenital heart disease.

  10. Evaluation of Germplasm Using SSR Markers of Functional Genes in Rice

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yong; YANG Kai; Akbar Ali Cheema; WENG Yue-jin

    2002-01-01

    16 SSR (Simple sequence repeats) primers of functional genes in rice were used to detect genetic diversity among 23 accessions of rice germplasm from 5 countries in the world. The average number of alleles per SSR locus was 5.2 with a range from 2 to 10. Genetic similarities among the 23 rice accessions ranged from 0.13 to 0.64. UPGMA cluster analysis showed that the 23 rice accessions could be classified into two distinct classes at similarities with a coefficient of 0.13. The Japonicas from Brazil, Japan and China were classified into Class I, along with upland rice from Brazil. The Indicas from Pakistan and Korea were classified into Class Ⅱ. Consequently, the function of genes SSR markers could be used as a useful tool for measuring genetic diversity, assigning rice to geographical distribution, ecotype, and pedigree relationship.

  11. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy.

    Science.gov (United States)

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L; Simpatico, Thomas; Gold, Mark S

    2015-06-01

    Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.

  12. Molecular Characterization and Functional Analysis of a Putative Octopamine/Tyramine Receptor during the Developmental Stages of the Pacific Oyster, Crassostrea gigas

    Science.gov (United States)

    Ji, Peng; Xu, Fei; Huang, Baoyu; Li, Yingxiang; Li, Li; Zhang, Guofan

    2016-01-01

    Octopamine (OA) and its precursor, tyramine (TA), participate in invertebrate development such as growth, maturation, and reproduction by activating their corresponding G protein-coupled receptors (GPCRs). Although OA was first discovered in mollusks (octopus), subsequent studies on OA, TA and related receptors have primarily been conducted in Ecdysozoa, especially in insects. Accordingly, only limited reports on OA/TA receptors in mollusks are available and their physiological roles remain unclear. Here, a full-length cDNA encoding a putative 524 amino acid OA/TA receptor (CgGPR1) was isolated from the Pacific oyster Crassostrea gigas. CgGPR1 was most closely related to the Lymnaea stagnalis OA receptor OAR2 in sequence. Phylogenetic analysis showed that CgGPR1 belongs to a poorly studied subfamily of invertebrate OA/TA receptors. The spatio-temporal expression of CgGPR1 in C. gigas larvae was examined by quantitative real-time PCR and Western blot analysis. CgGPR1 was expressed during all developmental stages of C. gigas with higher levels at mid-developmental stages, indicating its potential role in embryogenesis and tissue differentiation. Immunoreactive fluorescence of CgGPR1 was mainly observed in the velum, foot, gill and mantle of C. gigas larvae. CgGPR1 transcripts were detected in all the tested organs of adult C. gigas, with highest level in the mantle. Pharmacological analysis showed that cAMP and Ca2+ concentrations remained unchanged in HEK293 cells expressing CgGPR1 upon addition of OA, TA or related amines, suggesting that CgGPR1 modulates other unknown molecules rather than cAMP and Ca2+. Our study sheds light on CgGPR1 function in oysters. PMID:27992549

  13. Reassessment of the toxin profile of Cylindrospermopsis raciborskii T3 and function of putative sulfotransferases in synthesis of sulfated and sulfonated PSP toxins.

    Science.gov (United States)

    Soto-Liebe, Katia; Murillo, Alejandro A; Krock, Bernd; Stucken, Karina; Fuentes-Valdés, Juan J; Trefault, Nicole; Cembella, Allan; Vásquez, Mónica

    2010-12-01

    The toxigenic freshwater cyanobacterium Cylindrospermopsis raciborskii T3 has been used as a model to study and elucidate the biosynthetic pathway of tetrahydropurine neurotoxins associated with paralytic shellfish poisoning (PSP). There are nevertheless several inconsistencies and contradictions in the toxin profile of this strain as published by different research groups, and claimed to include carbamoyl (STX, NEO, GTX2/3), decarbamoyl (dcSTX), and N-sulfocarbamoyl (C1/2, B1) derivatives. Our analysis of the complete genome of another PSP toxin-producing cyanobacterium, Raphidiopsis brookii D9, which is closely related to C. raciborskii T3, resolved many issues regarding the correlation between biosynthetic pathways, corresponding genes and the T3 toxin profile. The putative sxt gene cluster in R. brookii D9 has a high synteny with the T3 sxt cluster, with 100% nucleotide identity among the shared genes. We also compared the PSP toxin profile of the strains by liquid chromatography coupled to mass spectrometry (LC-MS/MS). In contrast to published reports, our reassessment of the PSP toxin profile of T3 confirmed production of only STX, NEO and dcNEO. We gained significant insights via correlation between specific sxt genes and their role in PSP toxin synthesis in both D9 and T3 strains. In particular, analysis of sulfotransferase functions for SxtN (N-sulfotransferase) and SxtSUL (O-sulfotransferase) enzymes allowed us to propose an extension of the PSP toxin biosynthetic pathway from STX to the production of the derivatives GTX2/3, C1/2 and B1. This is a significantly revised view of the genetic mechanisms underlying synthesis of sulfated and sulfonated STX analogues in toxigenic cyanobacteria.

  14. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1

    Science.gov (United States)

    Meyer, Kerstin B.; O’Reilly, Martin; Michailidou, Kyriaki; Carlebur, Saskia; Edwards, Stacey L.; French, Juliet D.; Prathalingham, Radhika; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; de Santiago, Ines; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Van ’t Veer, Laura J.; Hogervorst, Frans B.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Lux, Michael P.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias, Jose I.; Benitez, Javier; Neuhausen, Susan; Anton-Culver, Hoda; Ziogas, Argyrios; Dur, Christina C.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Engel, Christoph; Ditsch, Nina; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Dörk, Thilo; Helbig, Sonja; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Thienpont, Bernard; Christiaens, Marie-Rose; Smeets, Ann; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Bernard, Loris; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Purrington, Kristen; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo-Hwang; Yip, Cheng-Har; Phuah, Sze-Yee; Kristensen, Vessela; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline M.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Darabi, Hartef; Eriksson, Kimael; Hooning, Maartje J.; Martens, John W.M.; van den Ouweland, Ans M.W.; van Deurzen, Carolien H.M.; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Ghoussaini, Maya; Harrington, Patricia; Tyrer, Jonathan; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Hui, Miao; Lim, Wei-Yen; Buhari, Shaik A.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Vachon, Celine; Slager, Susan; Fostira, Florentia; Pilarski, Robert; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Dunning, Alison M.; Easton, Douglas F.

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease. PMID:24290378

  15. Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Mwila Mulubwa

    2016-02-01

    Full Text Available Background: Tenofovir disoproxil fumarate (TDF has been associated with kidney tubulardys function and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV concentration with renal function; no such studies to date have been performed on Africans.Objective: To investigate the correlation between plasma tenofovir (TFV concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART.These markers were also compared to a HIV-uninfected control group.Methods: HIV-infected women (n = 30 on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR, creatinine clearance (CrCl, serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses.Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001 in HIV-infected women. In the adjusted (weight analysis, eGFR (p = 0.038,CrCl (p = 0.032 and albuminuria (p = 0.048 were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001 and CrCl (p = 0.008 increased from baseline to follow-up in HIV-infected women.Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

  16. Clinical and Biochemical Markers of Cardiovascular Structure and Function in Women With the Metabolic Syndrome.

    Science.gov (United States)

    Velarde, Gladys P; Sherazi, Saadia; Kraemer, Dale F; Bravo-Jaimes, Katia; Butterfield, Ryan; Amico, Tonja; Steinmetz, Sherry D; Guzman, Maricela; Martin, Dale; Dodani, Sunita; Smith, Brian H

    2015-12-01

    The pathobiological impact of individual components of the metabolic syndrome (MS) on cardiac structural and functional parameters in women with isolated MS is not known. The objectives of this study were (1) to compare biochemical (prothrombotic, lipogenic, and inflammatory) and imaging (carotid intima-media thickening and basic cardiac structural measurements) markers in women with and without MS and (2) to examine if any of these markers associated or predicted cardiac structural differences between the 2 groups. This cross-sectional pilot study included 88 women with MS and 35 women without it. MS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Patients with diagnosis of diabetes were excluded. Compared with healthy subjects, women with MS had higher levels of intercellular adhesion molecule, myeloperoxidase, C-reactive protein, plasminogen activator inhibitor-1, leptin, apolipoprotein-B, and lower levels of apolipoprotein-A1 (p women with isolated MS compared with those without. Waist circumference and systolic BP had the strongest association with cardiac structural differences in this group of women.

  17. Functional validation of putative toxin-antitoxin genes from the Gram-positive pathogen Streptococcus pneumoniae: phd-doc is the fourth bona-fide operon

    Directory of Open Access Journals (Sweden)

    Wai Ting eChan

    2014-12-01

    Full Text Available Bacterial toxin-antitoxin (TAs loci usually consist of two genes organized as an operon, where their products are bound together and inert under normal conditions. However, under stressful circumstances the antitoxin, which is more labile, will be degraded more rapidly, thereby unleashing its cognate toxin to act on the cell. This, in turn, causes cell stasis or cell death, depending on the type of TAs and/or time of toxin exposure. Previously based on in silico analyses, we proposed that Streptococcus pneumoniae, a pathogenic Gram-positive bacterium, may harbor between four to ten putative TA loci depending on the strains. Here we have chosen the pneumococcal strain Hungary19A-6 which contains all possible ten TA loci. In addition to the three well-characterized operons, namely relBE2, yefM-yoeB, and pezAT, we show here the functionality of a fourth operon that encodes the pneumococcal equivalent of the phd-doc TA. Transcriptional fusions with gene encoding Green Fluorescent Protein showed that the promoter was slightly repressed by the Phd antitoxin, and exhibited almost background values when both Phd-Doc were expressed together. These findings demonstrate that phd-doc shows the negative self-regulatory features typical for an authentic TA. Further, we also show that the previously proposed TAs XreA-Ant and Bro-XreB, although they exhibit a genetic organization resembling those of typical TAs, did not appear to confer a functional behavior corresponding to bona fide TAs. In addition, we have also discovered new interesting bioinformatics results for the known pneumococcal TAs RelBE2 and PezAT. A global analysis of the four identified toxins-antitoxins in the pneumococcal genomes (PezAT, RelBE2, YefM-YoeB, and Phd-Doc showed that RelBE2 and Phd-Doc are the most conserved ones. Further, there was good correlation among TA types, clonal complexes and sequence types in the 48 pneumococcal strains analyzed.

  18. Developmentally sensitive markers of personality functioning in adolescents: Age-specific and age-neutral expressions.

    Science.gov (United States)

    Debast, Inge; Rossi, Gina; Feenstra, Dineke; Hutsebaut, Joost

    2017-04-01

    Criterion D of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association [APA], 2013) refers to a possible onset of personality disorders (PDs) in adolescence and in Section II the development/course in adolescence is described by some typical characteristics for several PDs. Yet, age-specific expressions of PDs are lacking in Section III. We urgently need a developmentally sensitive assessment instrument that differentiates developmental and contextual changes on the one hand from expressions of personality pathology on the other hand. Therefore we investigated which items of the Severity Indices for Personality Problems-118 (SIPP-118) were developmentally sensitive throughout adolescence and adulthood and which could be considered more age-specific markers requiring other content or thresholds over age groups. Applying item response theory (IRT) we detected differential item functioning (DIF) in 36% of the items in matched samples of 639 adolescents versus 639 adults. The DIF across age groups mainly reflected a different degree of symptom expressions for the same underlying level of functioning. The threshold for exhibiting symptoms given a certain degree of personality dysfunction was lower in adolescence for areas of personality functioning related to the Self and Interpersonal domains. Some items also measured a latent construct of personality functioning differently across adolescents and adults. This suggests that several facets of the SIPP-118 do not solely measure aspects of personality pathology in adolescents, but likely include more developmental issues. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Elucidation of functional markers from Aspergillus nidulans developmental regulator FlbB and their phylogenetic distribution.

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    Marc S Cortese

    Full Text Available Aspergillus nidulans is a filamentous fungus widely used as a model for biotechnological and clinical research. It is also used as a platform for the study of basic eukaryotic developmental processes. Previous studies identified and partially characterized a set of proteins controlling cellular transformations in this ascomycete. Among these proteins, the bZip type transcription factor FlbB is a key regulator of reproduction, stress responses and cell-death. Our aim here was the prediction, through various bioinformatic methods, of key functional residues and motifs within FlbB in order to inform the design of future laboratory experiments and further the understanding of the molecular mechanisms that control fungal development. A dataset of FlbB orthologs and those of its key interaction partner FlbE was assembled from 40 members of the Pezizomycotina. Unique features were identified in each of the three structural domains of FlbB. The N-terminal region encoded a bZip transcription factor domain with a novel histidine-containing DNA binding motif while the dimerization determinants exhibited two distinct profiles that segregated by class. The C-terminal region of FlbB showed high similarity with the AP-1 family of stress response regulators but with variable patterns of conserved cysteines that segregated by class and order. Motif conservation analysis revealed that nine FlbB orthologs belonging to the Eurotiales order contained a motif in the central region that could mediate interaction with FlbE. The key residues and motifs identified here provide a basis for the design of follow-up experimental investigations. Additionally, the presence or absence of these residues and motifs among the FlbB orthologs could help explain the differences in the developmental programs among fungal species as well as define putative complementation groups that could serve to extend known functional characterizations to other species.

  20. Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker

    Science.gov (United States)

    Karaca, Melis; Castel, Julien; Tourrel-Cuzin, Cécile; Brun, Manuel; Géant, Anne; Dubois, Mathilde; Catesson, Sandra; Rodriguez, Marianne; Luquet, Serge; Cattan, Pierre; Lockhart, Brian; Lang, Jochen; Ktorza, Alain

    2009-01-01

    Background The mass of pancreatic β-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous β-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of β-cells and investigated their physiological relevance in increased insulin demand conditions in rats. Methods Two rat β-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. βhigh and βlow-cells. Insulin release, Ca2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, βhigh and βlow-cell distribution and functionality were investigated in animal models with decreased or increased β-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. Results We show that β-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike βlow-cells, βhigh-cells express functional β-cell markers and are highly responsive to various insulin secretagogues. Whereas βlow-cells represent the main population in diabetic pancreas, an increase in βhigh-cells is associated with gain of function that follows sustained glucose overload. Conclusion Our data show that a functional heterogeneity of β-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in β-cell defects in type 2 diabetes. PMID:19440374

  1. Exploring functional beta-cell heterogeneity in vivo using PSA-NCAM as a specific marker.

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    Melis Karaca

    Full Text Available BACKGROUND: The mass of pancreatic beta-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous beta-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of beta-cells and investigated their physiological relevance in increased insulin demand conditions in rats. METHODS: Two rat beta-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. beta(high and beta(low-cells. Insulin release, Ca(2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, beta(high and beta(low-cell distribution and functionality were investigated in animal models with decreased or increased beta-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. RESULTS: We show that beta-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike beta(low-cells, beta(high-cells express functional beta-cell markers and are highly responsive to various insulin secretagogues. Whereas beta(low-cells represent the main population in diabetic pancreas, an increase in beta(high-cells is associated with gain of function that follows sustained glucose overload. CONCLUSION: Our data show that a functional heterogeneity of beta-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in beta-cell defects in type 2 diabetes.

  2. Structural and functional markers of health depending on lifestyle in elderly women from Poland

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    Skrzek A

    2015-04-01

    Full Text Available Anna Skrzek,1 Zofia Ignasiak,2 Teresa Sławińska,2 Jarosław Domaradzki,2 Jarosław Fugiel,2 Anna Sebastjan,2 Krystyna Rożek11Faculty of Physiotherapy, 2Faculty of Physical Education, University School of Physical Education in Wroclaw, Wroclaw, PolandObjective: To comparatively analyze the rate and magnitude of age-related changes between two groups of elderly women with different lifestyles living in Poland: women attending a University of the Third Age (active lifestyle and less-active peers not involved in any seniors association.Methods: The study was conducted in 2010–2012. The study design was approved by the Senate Ethics Committee for Scientific Research of the University School of Physical Education. In total, 417 women were recruited. Basic somatic characteristics, body composition, bone mineral density, physical fitness, respiratory function, postural stability, and body posture were measured. Regression analysis and Student’s t-tests for independent samples were calculated.Results and conclusion: The best results among the tests assessing functional biological markers of health were found in the group of elderly women attending a University of the Third Age. The rate of change was larger in the group of seniors leading a less-active lifestyle, indicating the important role of a preventive gerontological approach and the participation of seniors in programs that accentuate the need for physical activity. Keywords: age-related changes, bone mineral density, markers of health, lifestyle, elderly women

  3. Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborti, Subhendu; Bahnson, Brian J. (Delaware)

    2010-05-25

    Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been confirmed by mutagenesis of the metal coordinating residues. Kinetic studies using the substrate gluconolactone showed a k{sub cat} preference of divalent cations in the order Zn{sup 2+} > Mn{sup 2+} > Ca{sup 2+} > Mg{sup 2+}. Notably, the Ca{sup 2+} had a significantly higher value of K{sub d} compared to those of the other metal ions tested (566, 82, 7, and 0.6 {micro}m for Ca{sup 2+}, Mg{sup 2+}, Zn{sup 2+}, and Mn{sup 2+}, respectively), suggesting that the Ca{sup 2+}-bound form may be physiologically relevant for stressed cells with an elevated free calcium level.

  4. Functional visualization of the excretory system of adult Schistosoma mansoni by the fluorescent marker resorufin.

    Science.gov (United States)

    Sato, H; Kusel, J R; Thornhill, J

    2002-12-01

    Excretion of metabolic wastes as well as xenobiotics is a major concern of all living organisms, and the Platyhelminthes including Schistosoma mansoni possess the protonephridial excretory system for their survival. Except for some ultra-structural and biochemical information, little is known about the protonephridium of platyhelminths due to a lack of established techniques for exploring the excretory activity. This study describes a new technique to assess the excretory activity of S. mansoni by use of the fluorescent marker resorufin, which is a potential substrate of the drug efflux pump, P-glycoprotein. After simple diffusion into the schistosome body, fluorescent resorufin was concentrated in the excretory tubules by an energy-dependent mechanism and excreted via the nephridiopore. The present technique of labelling functionally the excretory system was applicable to adult worms, but not schistosomula or cercariae. A variety of modulators known to interfere with mammalian P-glycoprotein function perturbed resorufin excretion from male adult schistosomes, including cyclosporin A, Ro11-2933, verapamil, or nifedipine. This technique of labelling the excretory system with fluorescent resorufin has enabled us to study aspects of the physiological function, hitherto unknown, of the protonephridial system of S. mansoni.

  5. Renal function markers and thyroid hormone status in undialyzed chronic kidney disease

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    Balaji Rajagopalan

    2013-01-01

    Full Text Available Objective: The study was undertaken to quantify thyroid hormones in undialyzed chronic kidney disease patients’ verses controls and to study the correlation between renal function markers and thyroid hormones. Background: Chronic kidney disease (CKD is associated with a higher prevalence of primary hypothyroidism (HT, but at the same studies on thyroid hormone status in uremic patients has reported conflicting results. Methods: Thyroid hormones and renal function parameters like serum urea, creatinine, creatinine clearance, total protein and albumin were estimated and correlations between thyroid hormones and renal function parameters were studied in 60 undialyzed chronic kidney disease patients’ verses 100 healthy controls. Results: We found both T3 and T4 were significantly reduced (p<0.0001 for T3 and 0.007 for T4 whereas TSH remains to be unchanged in patient group compared to controls. We also observed that urea and creatinine were negatively correlated whereas creatinine clearance was positively correlated with both T3 and T4 that has high statistical (two-tailed significance at 0.01 level. But urea alone is negatively correlated with TSH that has statistical (two-tailed significance at 0.05 level. Conclusion: From our data, we speculate that renal insufficiency may lead to thyroid hormone disturbances.

  6. Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function: The MIREC Study.

    Science.gov (United States)

    Lavigne, Eric; Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E; Hystad, Perry; Johnson, Markey; Crouse, Dan L; Ettinger, Adrienne S; Shapiro, Gabriel D; Fisher, Mandy; Morisset, Anne-Sophie; Taback, Shayne; Bouchard, Maryse F; Sun, Liu; Monnier, Patricia; Dallaire, Renée; Fraser, William D

    2016-05-01

    Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m(3)) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored.

  7. Development of Simple Functional Markers for Low Glutelin Content Gene 1 (Lgc1) in Rice (Oryza sativa)

    Institute of Scientific and Technical Information of China (English)

    CHEN Tao; TIAN Meng-xiang; ZHANG Ya-dong; ZHU Zhen; ZHAO Ling; ZHAO Qing-yong; LIN Jing; ZHOU Li-hui; WANG Cai-lin

    2010-01-01

    Rice with low glutelin content is suitable as functional food for patients affected by kidney failure. Low glutelin- content gene Lgc1 in rice has a 3.5-kb deletion between two highly similar glutelin genes GluB4 and GluB5, which locates on the short arm of chromosome 2. To improve the selection efficiency in low glutelin-content rice breeding, two molecular markers designated as InDel-Lgc1-1 and InDel-Lgc1-2 were developed to detect the low glutelin-content gene Lgc1. A double PCR detection indicated that combined use of the two markers could easily distinguish the genotypes of Lgc1 from different rice varieties. Therefore, as a simple and low-cost technique, the molecular marker could be widely used to identify different varieties with Lgc1 gene and applied in marker-assisted selection of low glutelin-content rice.

  8. Radial basis function regression methods for predicting quantitative traits using SNP markers.

    Science.gov (United States)

    Long, Nanye; Gianola, Daniel; Rosa, Guilherme J M; Weigel, Kent A; Kranis, Andreas; González-Recio, Oscar

    2010-06-01

    A challenge when predicting total genetic values for complex quantitative traits is that an unknown number of quantitative trait loci may affect phenotypes via cryptic interactions. If markers are available, assuming that their effects on phenotypes are additive may lead to poor predictive ability. Non-parametric radial basis function (RBF) regression, which does not assume a particular form of the genotype-phenotype relationship, was investigated here by simulation and analysis of body weight and food conversion rate data in broilers. The simulation included a toy example in which an arbitrary non-linear genotype-phenotype relationship was assumed, and five different scenarios representing different broad sense heritability levels (0.1, 0.25, 0.5, 0.75 and 0.9) were created. In addition, a whole genome simulation was carried out, in which three different gene action modes (pure additive, additive+dominance and pure epistasis) were considered. In all analyses, a training set was used to fit the model and a testing set was used to evaluate predictive performance. The latter was measured by correlation and predictive mean-squared error (PMSE) on the testing data. For comparison, a linear additive model known as Bayes A was used as benchmark. Two RBF models with single nucleotide polymorphism (SNP)-specific (RBF I) and common (RBF II) weights were examined. Results indicated that, in the presence of complex genotype-phenotype relationships (i.e. non-linearity and non-additivity), RBF outperformed Bayes A in predicting total genetic values using SNP markers. Extension of Bayes A to include all additive, dominance and epistatic effects could improve its prediction accuracy. RBF I was generally better than RBF II, and was able to identify relevant SNPs in the toy example.

  9. Functional expression of SAV3818, a putative TetR-family transcriptional regulatory gene from Streptomyces avermitilis, stimulates antibiotic production in Streptomyces species.

    Science.gov (United States)

    Duong, Cac Thi Phung; Lee, Han-Na; Choi, Si-Sun; Lee, Sang Yup; Kim, Eung-Soo

    2009-02-01

    Avermectin and its analogs are major commercial antiparasitic agents in the fields of animal health, agriculture, and human infections. Previously, comparative transcriptome analysis between the low-producer S. avermitilis ATCC31267 and the high-producer S. avermitilis ATCC31780 using a S. avermitilis whole genome chip revealed that 50 genes were overexpressed at least two-fold higher in S. avermitilis ATCC31780. To verify the biological significance of some of the transcriptomics-guided targets, five putative regulatory genes were individually cloned under the strong-andconstitutive promoter of the Streptomyces expression vector pSE34, followed by the transformation into the lowproducer S. avermitilis ATCC31267. Among the putative genes tested, three regulatory genes including SAV213, SAV3818, and SAV4023 exhibited stimulatory effects on avermectin production in S. avermitilis ATCC31267. Moreover, overexpression of SAV3818 also stimulated actinorhodin production in both S. coelicolor M145 and S. lividans TK21, implying that the SAV3818, a putative TetR-family transcriptional regulator, could be a global upregulator acting in antibiotic production in Streptomyces species.

  10. Is there an Association between Peripheral Immune Markers and Structural/Functional Neuroimaging Findings?

    LENUS (Irish Health Repository)

    Frodl, Thomas

    2013-01-10

    OBJECTIVES: There is mounting evidence that inflammatory processes play a key role in emotional as well as cognitive dysfunctions. In this context, research employing magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MR spectroscopy) suggests a possible link between structural\\/functional anomalies in the brain and an increase of circulating inflammation markers. The present paper reviews this research, with particular focus on major depressive disorder (MDD), cognitive impairment in older adults, Alzheimer\\'s disease (AD) and schizophrenia. RESULTS: In MDD, cognitive impairment and AD, inflammatory processes have been found to be associated with both structural and functional anomalies, perhaps under the influence of environmental stress. Not enough research can suggest similar considerations in schizophrenia, although studies in mice and non-human primates support the belief that inflammatory responses generated during pregnancy can affect brain development and contribute to the etiology of schizophrenia. CONCLUSIONS: The present review suggests a link between inflammatory processes and MRI detected anomalies in the brain of individuals with MDD, older adults with cognitive impairment as well as of individuals with AD and schizophrenia.

  11. Expression and function of a CP339,818-sensitive K⁺ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia.

    Science.gov (United States)

    Sforna, Luigi; D'Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro; Franciolini, Fabio; Catacuzzeno, Luigi

    2015-04-01

    Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K(+) current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K(+) channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs). Copyright © 2015 the American Physiological Society.

  12. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz;

    2016-01-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  13. Anti-Müllerian Hormone as a Sensitive Marker of Ovarian Function in Young Cancer Survivors

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    Maryna Krawczuk-Rybak

    2013-01-01

    Full Text Available We evaluated ovarian function by measuring the levels of anti-Müllerian hormone (AMH, estradiol, and gonadotropins in 83 young women treated for cancer during childhood and adolescence, and classified according to post-treatment gonadal toxicity versus 38 healthy females. Results. The mean AMH values were lower in the entire cohort independently of the risk group as compared to the control, whereas FSH was elevated only in the high risk group. The lowest AMH values were noted in patients after bone marrow transplantation (BMT and those treated for Hodgkin lymphoma (HL. Nineteen patients (22.9% had elevated FSH. They all had low AMH values. Lowered AMH values (but with normal FSH and LH were observed in 43 patients (51.8%. There was no effect of age at the time of treatment (before puberty, during or after puberty on AMH levels. Conclusion. Our results show the utility of AMH measurement as a sensitive marker of a reduced ovarian reserve in young cancer survivors. Patients after BMT and patients treated for HL, independently of age at treatment (prepuberty or puberty, are at the highest risk of gonadal damage and early menopause.

  14. Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    Qi Pan; Hao Yu; Jian-Liang You

    2016-01-01

    Objective:To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods:A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases) and observation group (45 cases). The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d) for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups.Results:After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05), and the levels of immune function indexes (CD3+, CD4+, CD4+/CD8+) of the observation group were significantly higher than those in the control group (P<0.05). After treatment, the levels of two tumor markers (CEA, CA15-3) decreased significantly than before treatment in both groups (P<0.05), and the decrease amplitude in the observation group was higher than that in the control group (P<0.05).Conclusions:Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

  15. Functional Marker Assisted Improvement of Stable Cytoplasmic Male Sterile Lines of Rice for Bacterial Blight Resistance

    Directory of Open Access Journals (Sweden)

    Jegadeesan Ramalingam

    2017-06-01

    Full Text Available Bacterial blight (BB, caused by Xanthomonas oryzae pv.oryzae is one among the major diseases in rice, which in severe condition cause losses up to 60% in total yield. Marker assisted pyramiding of three broad spectrum BB resistance genes (xa5, xa13, and Xa21 in prominent rice varieties is the most economical and effective strategy for the management of the BB disease. We report here the pyramiding of three genes (xa5, xa13, and Xa21 in maintainer lines (CO 2B, CO 23B, and CO 24B of three promising wild abortive cytoplasmic male sterile lines (CO 2A, CO 23A, and CO 24A through functional markers assisted back cross breeding. IRBB60 with xa5, xa13, and Xa21 genes is used as a donor parent. BC2F1 and BC2F2 generations from a cross of CO 2B, CO 23B, and CO 24B with IRBB60 were evaluated for bacterial blight and non-fertility restoration. In BC2F1, plants with all three resistance genes (xa5, xa13, and Xa21 and high parent genome recovery was identified. In BC2F2, plants with all resistance genes and without fertility restorer (Rf3 and Rf4 were selected. Based on agronomic traits, BB resistance and maintenance of sterility, two plants each in CO 2B × IRBB60, CO 24B × IRBB60 and one plant in CO 23B × IRBB60 combinations were identified. The identified lines were crossed with respective male sterile lines for conversion of improved B line into CMS line through back-crossing, in addition to selfing. The plants with high recurrent genome and phenotypically similar to parental lines and sterile are being used for the hybrid rice development program. Currently, using these lines (improved CMS line, test crosses were made to develop new rice hybrids. Hybrids combinations viz., CO 23A × AD08009R and CO 24A × IET20898R were found to be stable at different locations with high yield. The R line used in this study has been introgressed with xa5, xa13, and Xa21 genes in a separate breeding program. These new hybrids with resistance against bacterial blight

  16. Smell identification function as a severity and progression marker in Alzheimer's disease.

    Science.gov (United States)

    Velayudhan, Latha; Pritchard, Megan; Powell, John F; Proitsi, Petroula; Lovestone, Simon

    2013-07-01

    Olfactory dysfunction, impaired smell identification in particular, is known as a diagnostic and a marker of conversion in Alzheimer's disease (AD). We aimed to evaluate the associations of olfactory identification impairments with cognition, illness severity, and progression in AD patients. Fifty-seven outpatients with late onset mild to moderate AD and 24 elderly non-demented controls (NDC) were assessed, at baseline and after three months, for Mini-Mental State Examination (MMSE), University of Pennsylvania Smell Identification Test (UPSIT), and Bristol Activities of Daily Living and Neuropsychiatry Inventory. AD participants were classified as Rapid Cognitive Decliners (RCD) defined on a priori with a loss of ≥2 points in MMSE within the previous six months. AD participants had lower olfactory scores than NDC. RCD had lower olfaction scores compared with Non-Rapid Cognitive Decliners (NRCD). Although the baseline UPSIT scores were associated with baseline MMSE scores, it did not interact significantly with change in MMSE over the follow-up period. Using a median split for olfactory scores, the AD participants were classified as Rapid Olfactory Progressors (ROP) (UPSIT ≤ 15) and Slow Olfactory Progressors correlating significantly with RCD/NRCD groups. The ROP group with higher olfactory impairment indicated more symptomatic illness or severity, i.e. lower cognition, higher functional dependence, and presence of behavioral symptoms. Our study supports association of smell identification function with cognition and its utility as an adjunct clinical measure to assess severity in AD. Further work, including larger longitudinal studies, is needed to explore its value in predicting AD progression.

  17. Integrative analysis for identification of shared markers from various functional cells/tissues for rheumatoid arthritis.

    Science.gov (United States)

    Xia, Wei; Wu, Jian; Deng, Fei-Yan; Wu, Long-Fei; Zhang, Yong-Hong; Guo, Yu-Fan; Lei, Shu-Feng

    2017-02-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease. So far, it is unclear whether there exist common RA-related genes shared in different tissues/cells. In this study, we conducted an integrative analysis on multiple datasets to identify potential shared genes that are significant in multiple tissues/cells for RA. Seven microarray gene expression datasets representing various RA-related tissues/cells were downloaded from the Gene Expression Omnibus (GEO). Statistical analyses, testing both marginal and joint effects, were conducted to identify significant genes shared in various samples. Followed-up analyses were conducted on functional annotation clustering analysis, protein-protein interaction (PPI) analysis, gene-based association analysis, and ELISA validation analysis in in-house samples. We identified 18 shared significant genes, which were mainly involved in the immune response and chemokine signaling pathway. Among the 18 genes, eight genes (PPBP, PF4, HLA-F, S100A8, RNASEH2A, P2RY6, JAG2, and PCBP1) interact with known RA genes. Two genes (HLA-F and PCBP1) are significant in gene-based association analysis (P = 1.03E-31, P = 1.30E-2, respectively). Additionally, PCBP1 also showed differential protein expression levels in in-house case-control plasma samples (P = 2.60E-2). This study represented the first effort to identify shared RA markers from different functional cells or tissues. The results suggested that one of the shared genes, i.e., PCBP1, is a promising biomarker for RA.

  18. A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance-functional analysis reveals the pathogenic one

    DEFF Research Database (Denmark)

    Kantelinen, Jukka; Hansen, Thomas V O; Kansikas, Minttu;

    2011-01-01

    Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative L...... identified VUS before predictive gene testing and genetic counseling are offered to a family.......Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS...... family carrying VUS in both MSH2 (c.2768T>A, p.Val923Glu) and MSH6 (c.3563G>A, p.Ser1188Asn). Two colorectal cancer (CRC) patients were studied for mutations and identified as carriers of both variants. In spite of a relatively high mean age of cancer onset (59.5 years) in the family, many CRC patients...

  19. Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Peralta Carmen A

    2011-01-01

    Full Text Available Abstract Background Defined as estimated glomerular filtration rate (eGFR Methods We tested cross-sectional associations between (eGFR and multiple hemostatic markers among 6751 participants representing a broad spectrum of kidney function in the Multi-Ethnic Study of Atherosclerosis (MESA. Kidney function was measured using cystatin C (eGFRcys or creatinine, using CKD Epidemiology Collaboration (eGFRcr. Hemostatic markers included soluble thrombomodulin (sTM, soluble tissue factor (sTF, D-Dimer, von Willebrand factor (vWF, factor VIII, plasmin-antiplasmin complex (PAP, tissue factor pathway inhibitor (TFPI, plasminogen activator inhibitor-1 (PAI-1, and fibrinogen. Associations were tested using multivariable linear regression with adjustment for demographics and comorbidities. Results In comparison to persons with eGFRcys >90 ml/min/1.73 m2, subjects with eGFRcys 2 had adjusted levels of sTM, sTF, D-Dimer, PAP, Factor VIII, TFPI, vWF and fibrinogen that were respectively 86%, 68%, 44%, 22%, 17%, 15%, 12% and 6% higher. Subjects with eGFRcys 60-90 ml/min/1.73 m2 had adjusted levels that were respectively 16%, 14%, 12%, 6%, 6%, 6%, 11% and 4% higher (p Conclusions Throughout a broad spectrum of kidney function, lower eGFR was associated with higher levels of hemostatic markers. Dysregulation of hemostasis may be a mechanism by which reduced kidney function promotes higher cardiovascular risk.

  20. Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells

    DEFF Research Database (Denmark)

    Pedersen, A W; Holmstrøm, K; Jensen, S S;

    2009-01-01

    The clinical use of dendritic cells (DCs) to induce antigen-specific immune tolerance has been hampered by the lack of a widely acknowledged method for generating human regulatory DCs but even more so by the non-existence of reliable markers. Thus, we set out to find reliable markers that can...... CD14 and reduced CD1a on the cell surface. These VD3-treated DCs exert a long-lasting inefficient T cell stimulation and induce T cell hyporesponsiveness with regulatory potential. Importantly, such VD3-treated DCs were readily distinguishable from untreated DCs by low levels of interleukin-23...

  1. Functional role of a putative carbonic anhydrase II-binding domain in the electrogenic Na+ -HCO₃- cotransporter NBCe1 expressed in Xenopus oocytes.

    Science.gov (United States)

    Yamada, Hideomi; Horita, Shoko; Suzuki, Masashi; Fujita, Toshiro; Seki, George

    2011-01-01

    The electrogenic Na+ -HCO₃⁻ cotransporter NBCe1 plays essential roles in the regulation of systemic and/or local pH. Homozygous inactivating mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. We recently showed that defective membrane expression of NBCe1, caused by several mutations such as Delta65bp (S982NfsX4), is also associated with familial migraine. The Delta65bp mutant is quite unique in that it lacks a putative carbonic anhydrase (CA) II-binding domain but still shows an apparently normal transport activity in Xenopus oocytes. In this addendum, we show that the co-expression of CAII together with the wild-type NBCe1 or the Delta65bp mutant does not enhance the NBCe1 activities in oocytes. Moreover, a carbonic anhydrase inhibitor acetazolamide fails to inhibit the wild-type or the Delta65bp activities co-expressed with CAII. These results indicate that a bicarbonate transport metabolon proposed for the interaction between CAII and NBCe1 does not work at least in Xenopus oocytes.

  2. Cloning and functional analysis of putative malonyl-CoA:acyl-carrier protein transacylase gene from the docosahexaenoic acid-producer Schizochytrium sp. TIO1101.

    Science.gov (United States)

    Cheng, Rubin; Ge, Yuqing; Yang, Bo; Zhong, Xiaoming; Lin, Xiangzhi; Huang, Zhen

    2013-06-01

    Malonyl-CoA:acyl-carrier protein transacylase (MCAT), which transfers the malonyl group from malonyl-CoA to holo-acyl carrier protein (ACP), is a key enzyme in fatty acid biosynthesis. Schizochytrium sp. TIO1101 is a marine protist with high levels of docosahexaenoic acid accumulation. In this study, the putative fabD gene coding MCAT was isolated from Schizochytrium sp. TIO1101. The Schizochytrium MCAT gene (ScTIOfabD) contained an 1176 bp open reading frame encoding a protein of 391 amino acids. The ScTIOfabD gene exhibited high novelty in nucleotide and amino acid sequence. The highest amino acid identity was only 35 % between ScTIOMCAT and the reported MCATs. Further studies demonstrated that ScTIOMCAT could bind malonyl-CoA directly and transfer malonyl group from malonyl-CoA to the ACP domain in vitro. Phylogenetic analysis suggested that ScTIOMCAT was relative close to MCATs of yeast strains. Overexpression of ScTIOMCAT in Saccharomyces cereviseae significantly increased the MCAT activity, without negative effects on the growth rate of the host strain. In addition, ScTIOMCAT generated 16.8 and 62 % increase in biomass and fatty acid accumulation, respectively, and did not alter the profile of fatty acid. Our results indicated that the novel MCAT gene from Schizochytrium sp. TIO1101 was crucial for fatty acid synthesis and had potential applications for genetic modifications of oil-producing species.

  3. Cloning of cellobiose phosphoenolpyruvate-dependent phosphotransferase genes: Functional expression in recombinant Escherichia coli and identification of a putative binding region for disaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Xiaokuang; Davis, F.C.; Ingram, L.O. [Univ. of Florida, Gainesville, FL (United States); Hespell, R.B. [USDA Agricultural Research Service, Peoria, IL (United States)

    1997-02-01

    Genomic libraries from nine cellobiose-metabolizing bacteria were screened for cellobiose utilization. Positive clones were recovered from six libraries, all of which encode phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) proteins. Clones from Bacillus subtilis, Butyrivibrio fibrisolvens, and Klebsiella oxytoca allowed the growth of recombinant Escherichia coli in cellobiose-M9 minimal medium. The K. oxytoca clone, pLOI1906, exhibited an unusually broad substrate range (cellobiose, arbutin, salicin, and methylumbelliferyl derivatives of glucose, cellobiose, mannose, and xylose) and was sequenced. The insert in this plasmid encoded the carboxy-terminal region of a putative regulatory protein, cellobiose permease (single polypeptide), and phospho-{beta}-glucosidase, which appear to form an operon (casRAB). Subclones allowed both casA and casB to be expressed independently, as evidenced by in vitro complementation. An analysis of the translated sequences from the EIIC domains of cellobiose, aryl-{beta}-glucoside, and other disaccharide permeases allowed the identification of a 50-amino-acid conserved region. A disaccharide consensus sequence is proposed for the most conserved segment (13 amino acids), which may represent part of the EIIC active site for binding and phosphorylation. 63 refs., 4 figs., 4 tabs.

  4. Association of Coffee Consumption with MRI Markers and Cognitive Function: A Population-Based Study

    NARCIS (Netherlands)

    L.F. Araújo (Larissa Fortunato); S.S. Mirza (Saira); D. Bos (Daniel); W.J. Niessen (Wiro); S.M. Barreto (Sandhi Maria); A. van der Lugt (Aad); M.W. Vernooij (Meike); A. Hofman (Albert); H.W. Tiemeier (Henning); M.A. Ikram (Arfan); Polidori, M.C. (M. Cristina)

    2016-01-01

    textabstractBackground: Coffee is one of the most widely consumed beverages worldwide and has been of considerable interest in research on cognition and dementia. Objective: To investigate the effect of coffee on preclinical brain MRI markers of dementia and cognitive performance. Methods: In 2,914

  5. Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity

    Science.gov (United States)

    Jiang, Hong; Liang, Ludan; Qin, Jing; Lu, Yingying; Li, Bingjue; Wang, Yucheng; Lin, Chuan; Zhou, Qin; Feng, Shi; Yip, Shun H.; Xu, Feng; Lai, EnYin; Wang, Junwen; Chen, Jianghua

    2016-01-01

    IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers, which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment. PMID:27127888

  6. PapR6, a putative atypical response regulator, functions as a pathway-specific activator of pristinamycin II biosynthesis in Streptomyces pristinaespiralis.

    Science.gov (United States)

    Dun, Junling; Zhao, Yawei; Zheng, Guosong; Zhu, Hong; Ruan, Lijun; Wang, Wenfang; Ge, Mei; Jiang, Weihong; Lu, Yinhua

    2015-02-01

    There are up to seven regulatory genes in the pristinamycin biosynthetic gene cluster of Streptomyces pristinaespiralis, which infers a complicated regulation mechanism for pristinamycin production. In this study, we revealed that PapR6, a putative atypical response regulator, acts as a pathway-specific activator of pristinamycin II (PII) biosynthesis. Deletion of the papR6 gene resulted in significantly reduced PII production, and its overexpression led to increased PII formation, compared to that of the parental strain HCCB 10218. However, either papR6 deletion or overexpression had very little effect on pristinamycin I (PI) biosynthesis. Electrophoretic mobility shift assays (EMSAs) demonstrated that PapR6 bound specifically to the upstream region of snaF, the first gene of the snaFE1E2GHIJK operon, which is likely responsible for providing the precursor isobutyryl-coenzyme A (isobutyryl-CoA) and the intermediate C11 αβ-unsaturated thioester for PII biosynthesis. A signature PapR6-binding motif comprising two 4-nucleotide (nt) inverted repeat sequences (5'-GAGG-4 nt-CCTC-3') was identified. Transcriptional analysis showed that inactivation of the papR6 gene led to markedly decreased expression of snaFE1E2GHIJK. Furthermore, we found that a mutant (snaFmu) with base substitutions in the identified PapR6-binding sequence in the genome exhibited the same phenotype as that of the ΔpapR6 strain. Therefore, it may be concluded that pathway-specific regulation of PapR6 in PII biosynthesis is possibly exerted via controlling the provision of isobutyryl-CoA as well as the intermediate C11 αβ-unsaturated thioester.

  7. Cloning of a putative extracellular Cu/Zn superoxide dismutase and functional differences of superoxide dismutases in invasive and indigenous whiteflies.

    Science.gov (United States)

    Gao, Xian-Long; Li, Jun-Min; Xu, Hong-Xing; Yan, Gen-Hong; Jiu, Min; Liu, Shu-Sheng; Wang, Xiao-Wei

    2015-02-01

    Superoxide dismutases (SODs) are a group of important antioxidant defense enzymes. In this study, a putative extracellular Cu/Zn superoxide dismutase (ecCuZnSOD) complementary DNA was cloned and characterized from the whitefly, Bemisia tabaci. Quantitative polymerase chain reaction analysis showed that the expression level of BtecCuZnSOD was more than 10-fold higher in the invasive Middle East Asia Minor 1 (MEAM1) than in the native Asia II 3 species of the B. tabaci species complex. After exposure to low temperature (4 °C), the expression of Bt-ecCuZnSOD gene was significantly up-regulated in MEAM1 but not in Asia II 3. Furthermore, the expression level of B. tabaci intracellular CuZnSOD (Bt-icCuZnSOD), Bt-ecCuZnSOD and mitochondrial MnSOD (Bt-mMnSOD) was compared after transferring MEAM1 and Asia II 3 whiteflies from favorable (cotton) to unfavorable host plants (tobacco). On cotton, both CuZnSOD genes were expressed at a higher level in MEAM1 compared with Asia II 3. Interestingly, after transferring onto tobacco, the expression of Bt-ecCuZnSOD was significantly induced in Asia II 3 but not in MEAM1. On the other hand, while Bt-mMnSOD was expressed equally in both species on cotton, Bt-mMnSOD messenger RNA was up-regulated in MEAM1 on tobacco. Consistently, enzymatic activity assays of CuZnSOD and MnSOD demonstrated that CuZnSOD might play an important protective role against oxidative stress in Asia II 3, whereas MnSOD activation was critical for MEAM1 whiteflies during host adaptation. Taken together, our results suggest that the successful invasion of MEAM1 is correlated with its constitutive high activity of CuZnSOD and inducible expression of MnSOD under stress conditions.

  8. Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    YU Xiaofang; XU Xialian; YE Zhibin

    2007-01-01

    In patients with chronic renal failure,whether they have had hemodialysis or not,the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with norrnal kidney function.The detection of tumor markers is extensively used for the diagnosis of corresponding tumors.It has been recently shown that some tumor markers are higher in patients with chronic kidney disease(END)than in the normal population.The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA,CA199,CA125,AFP,CA153,CA724,CYFRA21-1,NSE,SCC-Ag,PSA,and fPSA.The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study.The 232 non-dialysis patients were divided into three groups according to their Ccr.In group 1,Ccr was≤25 mL/min.In group 2,Ccr was between 25 and 50 mL/min.In group 3,Ccr was≥50 mL/min.The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups.Nine tumor markers in 37 uremic patients were tested.For comparison.37 non-dialysis patients with similar Ccr of the same age and gender served as controls.There existed significant difierences in serum levels of CEA,CA199,CYFRA21.1,NSE,and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr.There were no significant differences among the three groups in the serum concentrations of CA125,AFP,CA153,CA724,PSA and fPSA.The serum levels of CA125 and NSE were significantly higher(P<0.01)in hemodialysis patients than in the nondialysis control patients.In patients with chronic renal failure,who were or were not on hemodialysis,the specificity of serum CEA,CA199,CYFRA21-1,NSE,CA125 and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP,CA153,CA724,PSA and fPSA were as valuable as they were in

  9. Non-homologous end joining-mediated functional marker selection for DNA cloning in the yeast Kluyveromyces marxianus.

    Science.gov (United States)

    Hoshida, Hisashi; Murakami, Nobutada; Suzuki, Ayako; Tamura, Ryoko; Asakawa, Jun; Abdel-Banat, Babiker M A; Nonklang, Sanom; Nakamura, Mikiko; Akada, Rinji

    2014-01-01

    The cloning of DNA fragments into vectors or host genomes has traditionally been performed using Escherichia coli with restriction enzymes and DNA ligase or homologous recombination-based reactions. We report here a novel DNA cloning method that does not require DNA end processing or homologous recombination, but that ensures highly accurate cloning. The method exploits the efficient non-homologous end-joining (NHEJ) activity of the yeast Kluyveromyces marxianus and consists of a novel functional marker selection system. First, to demonstrate the applicability of NHEJ to DNA cloning, a C-terminal-truncated non-functional ura3 selection marker and the truncated region were PCR-amplified separately, mixed and directly used for the transformation. URA3(+) transformants appeared on the selection plates, indicating that the two DNA fragments were correctly joined by NHEJ to generate a functional URA3 gene that had inserted into the yeast chromosome. To develop the cloning system, the shortest URA3 C-terminal encoding sequence that could restore the function of a truncated non-functional ura3 was determined by deletion analysis, and was included in the primers to amplify target DNAs for cloning. Transformation with PCR-amplified target DNAs and C-terminal truncated ura3 produced numerous transformant colonies, in which a functional URA3 gene was generated and was integrated into the chromosome with the target DNAs. Several K. marxianus circular plasmids with different selection markers were also developed for NHEJ-based cloning and recombinant DNA construction. The one-step DNA cloning method developed here is a relatively simple and reliable procedure among the DNA cloning systems developed to date.

  10. Effects of oily fish intake on cardiovascular risk markers, cognitive function, and behavior in school-aged children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Lauritzen, Lotte; Hauger, Hanne

    2016-01-01

    pressure and fasting plasma triacylglycerol, which will be measured at baseline and endpoint. In addition, we will assess erythrocyte fatty acid composition (compliance), heart rate, plasma cholesterol, markers of glucose homeostasis, growth and body composition, dietary intake, and physical activity...... and sleep. We will also examine effects on cognitive function (attention, memory, and executive functions) by using standardized tests, behavior and emotions by administering parent-rated questionnaires and child interviews, and we will measure physiological stress response and cortisol levels. We need 150...

  11. Putative archaeal viruses from the mesopelagic ocean.

    Science.gov (United States)

    Vik, Dean R; Roux, Simon; Brum, Jennifer R; Bolduc, Ben; Emerson, Joanne B; Padilla, Cory C; Stewart, Frank J; Sullivan, Matthew B

    2017-01-01

    Oceanic viruses that infect bacteria, or phages, are known to modulate host diversity, metabolisms, and biogeochemical cycling, while the viruses that infect marine Archaea remain understudied despite the critical ecosystem roles played by their hosts. Here we introduce "MArVD", for Metagenomic Archaeal Virus Detector, an annotation tool designed to identify putative archaeal virus contigs in metagenomic datasets. MArVD is made publicly available through the online iVirus analytical platform. Benchmarking analysis of MArVD showed it to be >99% accurate and 100% sensitive in identifying the 127 known archaeal viruses among the 12,499 viruses in the VirSorter curated dataset. Application of MArVD to 10 viral metagenomes from two depth profiles in the Eastern Tropical North Pacific (ETNP) oxygen minimum zone revealed 43 new putative archaeal virus genomes and large genome fragments ranging in size from 10 to 31 kb. Network-based classifications, which were consistent with marker gene phylogenies where available, suggested that these putative archaeal virus contigs represented six novel candidate genera. Ecological analyses, via fragment recruitment and ordination, revealed that the diversity and relative abundances of these putative archaeal viruses were correlated with oxygen concentration and temperature along two OMZ-spanning depth profiles, presumably due to structuring of the host Archaea community. Peak viral diversity and abundances were found in surface waters, where Thermoplasmata 16S rRNA genes are prevalent, suggesting these archaea as hosts in the surface habitats. Together these findings provide a baseline for identifying archaeal viruses in sequence datasets, and an initial picture of the ecology of such viruses in non-extreme environments.

  12. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...... was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case–control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism...

  13. Association of Coffee Consumption with MRI Markers and Cognitive Function: A Population-Based Study

    OpenAIRE

    Araújo, Larissa Fortunato; Mirza, Saira; Bos, Daniel; Niessen, Wiro; Barreto, Sandhi Maria; Van der Lugt, Aad; Vernooij, Meike; Hofman, Albert; Tiemeier, Henning; Ikram, Arfan,; Polidori, M. C.

    2016-01-01

    textabstractBackground: Coffee is one of the most widely consumed beverages worldwide and has been of considerable interest in research on cognition and dementia. Objective: To investigate the effect of coffee on preclinical brain MRI markers of dementia and cognitive performance. Methods: In 2,914 participants from the population-based Rotterdam Study (mean age: 59.3±7.2 years, 55 females), we assessed coffee consumption, performed brain MRI, and assessed cognition at baseline. To study cogn...

  14. Effects of ω-3 PUFAs Supplementation on Myocardial Function and Oxidative Stress Markers in Typical Rett Syndrome

    Directory of Open Access Journals (Sweden)

    Silvia Maffei

    2014-01-01

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder with a 300-fold increased risk rate for sudden cardiac death. A subclinical myocardial biventricular dysfunction has been recently reported in RTT by our group and found to be associated with an enhanced oxidative stress (OS status. Here, we tested the effects of the naturally occurring antioxidants ω-3 polyunsaturated fatty acids (ω-3 PUFAs on echocardiographic parameters and systemic OS markers in a population of RTT patients with the typical clinical form. A total of 66 RTT girls were evaluated, half of whom being treated for 12 months with a dietary supplementation of ω-3 PUFAs at high dosage (docosahexaenoic acid ~71.9 ± 13.9 mg/kg b.w./day plus eicosapentaenoic acid ~115.5 ± 22.4 mg/kg b.w./day versus the remaining half untreated population. Echocardiographic systolic longitudinal parameters of both ventricles, but not biventricular diastolic measures, improved following ω-3 PUFAs supplementation, with a parallel decrease in the OS markers levels. No significant changes in the examined echocardiographic parameters nor in the OS markers were detectable in the untreated RTT population. Our data indicate that ω-3 PUFAs are able to improve the biventricular myocardial systolic function in RTT and that this functional gain is partially mediated through a regulation of the redox balance.

  15. Effects of ω-3 PUFAs Supplementation on Myocardial Function and Oxidative Stress Markers in Typical Rett Syndrome

    Science.gov (United States)

    De Felice, Claudio; Montomoli, Barbara; Lunghetti, Stefano; Ciccoli, Lucia; Favilli, Roberto; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disorder with a 300-fold increased risk rate for sudden cardiac death. A subclinical myocardial biventricular dysfunction has been recently reported in RTT by our group and found to be associated with an enhanced oxidative stress (OS) status. Here, we tested the effects of the naturally occurring antioxidants ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on echocardiographic parameters and systemic OS markers in a population of RTT patients with the typical clinical form. A total of 66 RTT girls were evaluated, half of whom being treated for 12 months with a dietary supplementation of ω-3 PUFAs at high dosage (docosahexaenoic acid ~71.9 ± 13.9 mg/kg b.w./day plus eicosapentaenoic acid ~115.5 ± 22.4 mg/kg b.w./day) versus the remaining half untreated population. Echocardiographic systolic longitudinal parameters of both ventricles, but not biventricular diastolic measures, improved following ω-3 PUFAs supplementation, with a parallel decrease in the OS markers levels. No significant changes in the examined echocardiographic parameters nor in the OS markers were detectable in the untreated RTT population. Our data indicate that ω-3 PUFAs are able to improve the biventricular myocardial systolic function in RTT and that this functional gain is partially mediated through a regulation of the redox balance. PMID:24526821

  16. Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

    Science.gov (United States)

    2014-10-01

    between brain function and connectivity in selective pathways/circuits, neuropsychological functioning, and cognitive rehabilitation response in...function and connectivity in selective pathways/circuits, neuropsychological functioning, and cognitive rehabilitation response in Veterans with both...data are collected.  We have started to examine cross-sectional baseline data on fMRI, EEG, and neuropsychological functioning with respect to

  17. The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Card, G L; Peterson, N A; Smith, C A; Rupp, B; Schick, B M; Baker, E N

    2005-02-15

    Mycobacterium tuberculosis, the cause of TB, is a devastating human pathogen. The emergence of multi-drug resistance in recent years has prompted a search for new drug targets and for a better understanding of mechanisms of resistance. Here we focus on the gene product of an open reading frame from M. tuberculosis, Rv1347c, which is annotated as a putative aminoglycoside N-acetyltransferase. The Rv1347c protein does not show this activity, however, and we show from its crystal structure, coupled with functional and bioinformatic data, that its most likely role is in the biosynthesis of mycobactin, the M. tuberculosis siderophore. The crystal structure of Rv1347c was determined by MAD phasing from selenomethionine-substituted protein and refined at 2.2 {angstrom} resolution (R = 0.227, R{sub free} = 0.257). The protein is monomeric, with a fold that places it in the GCN5-related N-acetyltransferase (GNAT) family of acyltransferases. Features of the structure are an acylCoA binding site that is shared with other GNAT family members, and an adjacent hydrophobic channel leading to the surface that could accommodate long-chain acyl groups. Modeling the postulated substrate, the N{sup {var_epsilon}}-hydroxylysine side chain of mycobactin, into the acceptor substrate binding groove identifies two residues at the active site, His130 and Asp168, that have putative roles in substrate binding and catalysis.

  18. Effects of oily fish intake on cardiovascular risk markers, cognitive function, and behavior in school-aged children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Lauritzen, Lotte; Hauger, Hanne;

    2016-01-01

    and sleep. We will also examine effects on cognitive function (attention, memory, and executive functions) by using standardized tests, behavior and emotions by administering parent-rated questionnaires and child interviews, and we will measure physiological stress response and cortisol levels. We need 150...... and behavior. However, to our knowledge, the potential effects of oily fish on cardiometabolic health, cognitive function, and behavior in children have not been investigated. The aim of the FiSK Junior study is to investigate the effects of oily fish consumption on cardiovascular risk markers, cognitive...... function, and behavior in healthy children. Methods/design We are conducting a randomized controlled trial with 8- to 9-year-old Danish children, comparing the effect of consuming 300 g/week of oily fish with poultry (control) for 12 weeks between August 2016 and June 2017. The primary outcomes are blood...

  19. Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.

    Science.gov (United States)

    Mike, Agnes K; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D; Weitzer, Georg; Hilber, Karlheinz

    2014-01-01

    Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  20. Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: relationships to resting-state functional connectivity

    Science.gov (United States)

    Moeller, Scott J.; London, Edythe D.; Northoff, Georg

    2015-01-01

    Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. PMID:26657968

  1. Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity.

    Science.gov (United States)

    Moeller, Scott J; London, Edythe D; Northoff, Georg

    2016-02-01

    Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. RNA-seq analysis of Quercus pubescens Leaves: de novo transcriptome assembly, annotation and functional markers development.

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    Sara Torre

    Full Text Available Quercus pubescens Willd., a species distributed from Spain to southwest Asia, ranks high for drought tolerance among European oaks. Q. pubescens performs a role of outstanding significance in most Mediterranean forest ecosystems, but few mechanistic studies have been conducted to explore its response to environmental constrains, due to the lack of genomic resources. In our study, we performed a deep transcriptomic sequencing in Q. pubescens leaves, including de novo assembly, functional annotation and the identification of new molecular markers. Our results are a pre-requisite for undertaking molecular functional studies, and may give support in population and association genetic studies. 254,265,700 clean reads were generated by the Illumina HiSeq 2000 platform, with an average length of 98 bp. De novo assembly, using CLC Genomics, produced 96,006 contigs, having a mean length of 618 bp. Sequence similarity analyses against seven public databases (Uniprot, NR, RefSeq and KOGs at NCBI, Pfam, InterPro and KEGG resulted in 83,065 transcripts annotated with gene descriptions, conserved protein domains, or gene ontology terms. These annotations and local BLAST allowed identify genes specifically associated with mechanisms of drought avoidance. Finally, 14,202 microsatellite markers and 18,425 single nucleotide polymorphisms (SNPs were, in silico, discovered in assembled and annotated sequences. We completed a successful global analysis of the Q. pubescens leaf transcriptome using RNA-seq. The assembled and annotated sequences together with newly discovered molecular markers provide genomic information for functional genomic studies in Q. pubescens, with special emphasis to response mechanisms to severe constrain of the Mediterranean climate. Our tools enable comparative genomics studies on other Quercus species taking advantage of large intra-specific ecophysiological differences.

  3. Daily kiwifruit consumption did not improve blood pressure and markers of cardiovascular function in men with hypercholesterolemia.

    Science.gov (United States)

    Gammon, Cheryl S; Kruger, Rozanne; Brown, Stephen J; Conlon, Cathryn A; von Hurst, Pamela R; Stonehouse, Welma

    2014-03-01

    Increasing fruit and vegetable consumption is a key lifestyle modification in the prevention and treatment of hypertension. Kiwifruit has previously been shown to have favorable effects on blood pressure (BP), likely through inhibiting angiotensin I-converting enzyme activity. We hypothesized that the replacement of 2 fruit servings in a healthy diet with 2 green kiwifruit a day would significantly improve BP and other markers of cardiovascular function, including heart rate, stroke volume, cardiac output, and total peripheral resistance, in a group of hypercholesterolemic men. Using a controlled cross-over study design, 85 subjects completed a 4-week healthy diet run-in period before randomization to one of two 4-week intervention sequences in which they either consumed 2 green kiwifruit a day plus a healthy diet (intervention) or consumed a healthy diet alone (control). Blood pressure and other measures of cardiovascular function (using a Finometer MIDI [Finapres Medical Systems B.V, Amsterdam, The Netherlands] and standard oscillometric device) and anthropometric measurements were taken before and at the end of the treatment periods. A physical activity questionnaire was completed during the last visit. Subjects were found to be predominantly normotensive (43.5%) or prehypertensive (50.6%) and quite physically active (>30 minutes of moderate to vigorous physical activity/day in >80% subjects). No significant differences were seen for BP or any of the other markers, including heart rate, stroke volume, cardiac output, and total peripheral resistance. In conclusion, in this hypercholesterolemic, nonhypertensive group, no beneficial effects on BP or other markers of cardiovascular function were seen when consuming 2 kiwifruit a day against the background of a healthy diet.

  4. Respiratory sinus arrhythmia: a marker for positive social functioning and receptive language skills in children with autism spectrum disorders.

    Science.gov (United States)

    Patriquin, Michelle A; Scarpa, Angela; Friedman, Bruce H; Porges, Stephen W

    2013-03-01

    The current study builds on the emerging autism spectrum disorder (ASD) literature that associates autonomic nervous system activity with social function, and examines the link between respiratory sinus arrhythmia (RSA) and both social behavior and cognitive function. The RSA response pattern was assessed in 23 4- to 7-year-old children diagnosed with an ASD. Higher baseline RSA amplitudes were associated with better social behavior (i.e., more conventional gestures, more instances of joint attention) and receptive language abilities. Similar to reports of typically developing children, ASD children with higher RSA amplitude at baseline showed greater RSA and HP reactivity during an attention-demanding task. These results highlight the importance of studying RSA as a marker of positive function in children with ASD.

  5. Endothelial progenitor cells as a new marker of endothelial function with respect to risk of cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Barbara Głowińska-Olszewska

    2011-01-01

    Full Text Available The discovery of endothelial progenitor cells (EPC, over a decade ago, has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The results of several studies revealed altered number and impaired function of EPC in hyperlipidemia, hypertension, diabetes, obesity as well as in rheumatoid arthritis. The population of developmental age is characterized by higher counts of EPC compared to adults. However, among young patients with chronic disorders that affect the vascular system, the number of EPC decreases. The reduced circulating concentration of EPC has become a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases. This article aims to review the biology and pathophysiology of EPC in the conditions of cardiovascular risk factors. The potential possibilities of increasing EPC number and function as well as the use of EPC in the treatment of vascular pathology will also be discussed.

  6. Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Schwingshackl, Lukas; Christoph, Marina; Hoffmann, Georg

    2015-09-11

    The aim of the present systematic review was to synthesize data from randomized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function. Literature search in electronic databases Cochrane Trial Register, EMBASE, and MEDLINE was performed. Thirty studies enrolling 3106 participants fulfilled the selection criteria. Pooled effects of different interventions were assessed as mean difference using a random effects model. Olive oil interventions (with daily consumption ranging approximately between 1 mg and 50 mg) resulted in a significantly more pronounced decrease in C-reactive protein (mean difference: -0.64 mg/L, (95% confidence interval (CI) -0.96 to -0.31), p olive oil interventions (mean difference: 0.76% (95% CI 0.27 to 1.24), p olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function, thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet. However, due to the heterogeneous study designs (e.g., olive oil given as a supplement or as part of dietary pattern, variations in control diets), a conservative interpretation of the results is necessary.

  7. Identification and analysis of unitary loss of long-established protein-coding genes in Poaceae shows evidences for biased gene loss and putatively functional transcription of relics.

    Science.gov (United States)

    Zhao, Yi; Tang, Liang; Li, Zhe; Jin, Jinpu; Luo, Jingchu; Gao, Ge

    2015-04-18

    Long-established protein-coding genes may lose their coding potential during evolution ("unitary gene loss"). Members of the Poaceae family are a major food source and represent an ideal model clade for plant evolution research. However, the global pattern of unitary gene loss in Poaceae genomes as well as the evolutionary fate of lost genes are still less-investigated and remain largely elusive. Using a locally developed pipeline, we identified 129 unitary gene loss events for long-established protein-coding genes from four representative species of Poaceae, i.e. brachypodium, rice, sorghum and maize. Functional annotation suggested that the lost genes in all or most of Poaceae species are enriched for genes involved in development and response to endogenous stimulus. We also found that 44 mutated genomic loci of lost genes, which we referred as relics, were still actively transcribed, and of which 84% (37 of 44) showed significantly differential expression across different tissues. More interestingly, we found that there were totally five expressed relics may function as competitive endogenous RNA in brachypodium, rice and sorghum genome. Based on comparative genomics and transcriptome data, we firstly compiled a comprehensive catalogue of unitary gene loss events in Poaceae species and characterized a statistically significant functional preference for these lost genes as well showed the potential of relics functioning as competitive endogenous RNAs in Poaceae genomes.

  8. Isolation, cloning and sequencing of AFLP markers related to disease-resistance traits in Fenneropenaeus chinensis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Amplified fragment length polymorphisms (AFLP) technique was used to analyze the fingerprinting of four successive generations of Fenneropenaeus chinensis to reveal their disease-resistance traits. Some loci showed quite different genetic frequencies due to artificial selection, which implied that these fragments were putative markers related to the disease-resistance trait. We developed a simple and effective method to further characterize these AFLP fragments. Specific AFLP bands were cut directly from polyacrylamide gels,re-amplified, cloned and sequenced. Eight putative genetic markers were sequenced and their sizes ranged from 63 to 209 bp. The sequences were submitted to dbGSS (database of Genome Sequence Survey); and the BLAST analysis showed low similarity to the function genes, indicating these markers were tightly linked to a disease-resistance trait but were not functional genes.

  9. An Investigation of Pragmatic Functions and Position of Prevalent Persian Discourse Markers Used in Casual Conversations among Tehrani Speakers

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    Manizheh Alami

    2016-01-01

    Full Text Available Given that a systematic treatment of Persian Discourse Markers (hereafter DMs is almost absent in modern Persian linguistics and to bridge this gap, the audio-recorded data comprising 14 face to face casual conversations involving two-party and multi-party interactions among family members, acquaintances and close friends are used to shed light on these ‘frequently used’ but ‘frequently unnoticed’ linguistic elements. To document a list of the most common DMs typically used in Tehrani dialect of Persian language and to have a detailed description of their discoursal functions in talk, Brinton’s (1996 binary classification of DMs functions (textual and interpersonal was developed to provide an empirically-supported account of the functions and position of Persian DMs in interaction among Tehrani speakers. The present account of DMs which is basically ‘analytical description’ provides the reader with the knowledge about how Persian DMs operate in actual usage. The findings are built upon a 3105-word corpus including 14 audio-recorded conversations among 50 participants. Altogether 34 tokens of Persian DMs with an overall 254 occurrences were identified among which na/na baba (no/no daddy with the total of 33 (12.84% occurrences were the most frequently used Persian DM in the data which are followed by dige (no English equivalent, aare/ba’ale (yep/yes, yani (I mean, vali (but, haalaa/ alaan (now, bebin/nega kon (look and aslan (by no means/ never.To the author, research on the functions and distributional patterns of Persian DMs will broaden our knowledge of their discoursal behavior in language in general and contribute to the already growing cross-linguistic body of work on DMs. Keywords: Discourse Markers, Persian language, Textual function, Interpersonal function, Casual conversation

  10. A Functional Approach to Pragmatic Markers in Discourse%话语中语用标记的功能分析

    Institute of Scientific and Technical Information of China (English)

    王雅琪

    2013-01-01

    Interpersonal communication is characterized by our special discourse. Among all the researches on it, an indispensable part of auxiliary one is pragmatic marker. It is generally considered to be their function of marking relationships among units of discourse.

  11. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action

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    Wolf Yuri I

    2006-03-01

    Full Text Available Abstract Background All archaeal and many bacterial genomes contain Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR and variable arrays of the CRISPR-associated (cas genes that have been previously implicated in a novel form of DNA repair on the basis of comparative analysis of their protein product sequences. However, the proximity of CRISPR and cas genes strongly suggests that they have related functions which is hard to reconcile with the repair hypothesis. Results The protein sequences of the numerous cas gene products were classified into ~25 distinct protein families; several new functional and structural predictions are described. Comparative-genomic analysis of CRISPR and cas genes leads to the hypothesis that the CRISPR-Cas system (CASS is a mechanism of defense against invading phages and plasmids that functions analogously to the eukaryotic RNA interference (RNAi systems. Specific functional analogies are drawn between several components of CASS and proteins involved in eukaryotic RNAi, including the double-stranded RNA-specific helicase-nuclease (dicer, the endonuclease cleaving target mRNAs (slicer, and the RNA-dependent RNA polymerase. However, none of the CASS components is orthologous to its apparent eukaryotic functional counterpart. It is proposed that unique inserts of CRISPR, some of which are homologous to fragments of bacteriophage and plasmid genes, function as prokaryotic siRNAs (psiRNA, by base-pairing with the target mRNAs and promoting their degradation or translation shutdown. Specific hypothetical schemes are developed for the functioning of the predicted prokaryotic siRNA system and for the formation of new CRISPR units with unique inserts encoding psiRNA conferring immunity to the respective newly encountered phages or plasmids. The unique inserts in CRISPR show virtually no similarity even between closely related bacterial strains which suggests their rapid turnover, on evolutionary scale

  12. Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal Precursor Cells

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    Tara L. Walker

    2016-04-01

    Full Text Available Here, we show that the lysophosphatidic acid receptor 1 (LPA1 is expressed by a defined population of type 1 stem cells and type 2a precursor cells in the adult mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have enabled the prospective separation of both proliferative and non-proliferative precursor cell populations. Transcriptional profiling of the isolated proliferative precursor cells suggested immune mechanisms and cytokine signaling as molecular regulators of adult hippocampal precursor cell proliferation. In addition to LPA1 being a marker of this important stem cell population, we also show that the corresponding ligand LPA is directly involved in the regulation of adult hippocampal precursor cell proliferation and neurogenesis, an effect that can be attributed to LPA signaling via the AKT and MAPK pathways.

  13. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Science.gov (United States)

    2012-01-01

    Background Arbuscular mycorrhizas (AM) are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis. PMID:23046713

  14. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Directory of Open Access Journals (Sweden)

    Giovannetti Marco

    2012-10-01

    Full Text Available Abstract Background Arbuscular mycorrhizas (AM are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis.

  15. Mutation of putative N-linked glycosylation sites on the human nucleotide receptor P2X7 reveals a key residue important for receptor function.

    Science.gov (United States)

    Lenertz, Lisa Y; Wang, Ziyi; Guadarrama, Arturo; Hill, Lindsay M; Gavala, Monica L; Bertics, Paul J

    2010-06-08

    The nucleotide receptor P2X(7) is an immunomodulatory cation channel and a potential therapeutic target. P2X(7) is expressed in immune cells such as monocytes and macrophages and is activated by extracellular ATP following tissue injury or infection. Ligand binding to P2X(7) can stimulate ERK1/2, the transcription factor CREB, enzymes linked to the production of reactive oxygen species and interleukin-1 isoforms, and the formation of a nonspecific pore. However, little is known about the biochemistry of P2X(7), including whether the receptor is N-linked glycosylated and if this modification affects receptor function. Here we provide evidence that P2X(7) is sensitive to the glycosidases EndoH and PNGase F and that the human receptor appears glycosylated at N187, N202, N213, N241, and N284. Mutation of N187 results in weakened P2X(7) agonist-induced phosphorylation of ERK1/2, CREB, and p90 ribosomal S6 kinase, as well as a decreased level of pore formation. In further support of a role for glycosylation in receptor function, treatment of RAW 264.7 macrophages with the N-linked glycosylation synthesis inhibitor tunicamycin attenuates P2X(7) agonist-induced, but not phorbol ester-induced, ERK1/2 phosphorylation. Interestingly, residue N187 belongs to an N-linked glycosylation consensus sequence found in six of the seven P2X family members, suggesting this site is fundamentally important to P2X receptor function. To address the mechanism whereby N187 mutation attenuates receptor activity, we developed a live cell proteinase K digestion assay that demonstrated altered cell surface expression of P2X(7) N187A. This is the first report to map human P2X(7) glycosylation sites and reveal residue N187 is critical for receptor trafficking and function.

  16. Identification of Putative ORF5 Protein of Porcine Circovirus Type 2 and Functional Analysis of GFP-Fused ORF5 Protein.

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    Qizhuang Lv

    Full Text Available Porcine circovirus type 2 (PCV2 is the essential infectious agent responsible for causing porcine circovirus-associated diseases in pigs. To date, eleven RNAs and five viral proteins of PCV2 have been detected. Here, we identified a novel viral gene within the PCV2 genome, termed ORF5, that exists at both the transcriptional and translational level during productive infection of PCV2 in porcine alveolar macrophages 3D4/2 (PAMs. Northern blot analysis was used to demonstrate that the ORF5 gene measures 180 bp in length and overlaps completely with ORF1 when read in the same direction. Site-directed mutagenesis was used to show that the ORF5 protein is not essential for PCV2 replication. To investigate the biological functions of the novel protein, we constructed a recombinant eukaryotic expression plasmid capable of expressing PCV2 ORF5. The results show that the GFP-tagged PCV2 ORF5 protein localizes to the endoplasmic reticulum (ER, is degraded via the proteasome, inhibits PAM growth and prolongs the S-phase of the cell cycle. Further studies show that the GFP-tagged PCV2 ORF5 protein induces ER stress and activates NF-κB, which was further confirmed by a significant upregulation in IL-6, IL-8 and COX-2 expression. In addition, five cellular proteins (GPNMB, CYP1A1, YWHAB, ZNF511 and SRSF3 were found to interact with ORF5 via yeast two-hybrid assay. These findings provide novel information on the identification and functional analysis of the PCV2 ORF5 protein and are likely to be of benefit in elucidating the molecular mechanisms of PCV2 pathogenicity. However, additional experiments are needed to validate the expression and function of the ORF5 protein during PCV2 infection in vitro before any definitive conclusion can be drawn.

  17. Molecular Modeling Approaches for Determining Gene Function: application to a Putative Poly-A Binding Protein from Leishmania amazonensis (LaPABP

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    Silva-Jr FP

    2002-01-01

    Full Text Available The great expansion in the number of genome sequencing projects has revealed the importance of computational methods to speed up the characterization of unknown genes. These studies have been improved by the use of three dimensional information from the predicted proteins generated by molecular modeling techniques. In this work, we disclose the structure-function relationship of a gene product from Leishmania amazonensis by applying molecular modeling and bioinformatics techniques. The analyzed sequence encodes a 159 aminoacids polypeptide (estimated 18 kDa and was denoted LaPABP for its high homology with poly-A binding proteins from trypanosomatids. The domain structure, clustering analysis and a three dimensional model of LaPABP, basically obtained by homology modeling on the structure of the human poly-A binding protein, are described. Based on the analysis of the electrostatic potential mapped on the model's surface and conservation of intramolecular contacts responsible for folding stabilization we hypothesize that this protein may have less avidity to RNA than it's L. major counterpart but still account for a significant functional activity in the parasite. The model obtained will help in the design of mutagenesis experiments aimed to elucidate the mechanism of gene expression in trypanosomatids and serve as a starting point for its exploration as a potential source of targets for a rational chemotherapy.

  18. Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

    Science.gov (United States)

    Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

    2017-01-01

    Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

  19. Pituitary gland height evaluated by MR in patients with {beta}-thalassemia major: a marker of pituitary gland function

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, M.I.; Metafratzi, Z.; Efremidis, S.C. [Dept. of Radiology, Univ. of Ioannina (Greece); Kiortsis, D.N. [Dept. of Physiology, Univ. of Ioannina (Greece); Bitsis, S.; Tsatoulis, A. [Dept. of Internal Medicine, Univ. of Ioannina (Greece)

    2001-12-01

    In transfusion-dependent {beta}-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with {beta}-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1-weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n=15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P<0.001). No statistically significant difference was found between thalassemic patients without hormone dysfunction (n=14) (mean 5.34; SD 1.52) and age- and gender-matched controls (mean 5.91; SD 1.06). We conclude that in thalassemic patients the pituitary gland height is an additional marker of pituitary gland function and might be useful in clinical management. (orig.)

  20. A computational procedure for functional characterization of potential marker genes from molecular data: Alzheimer's as a case study

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    Barla Annalisa

    2011-07-01

    Full Text Available Abstract Background A molecular characterization of Alzheimer's Disease (AD is the key to the identification of altered gene sets that lead to AD progression. We rely on the assumption that candidate marker genes for a given disease belong to specific pathogenic pathways, and we aim at unveiling those pathways stable across tissues, treatments and measurement systems. In this context, we analyzed three heterogeneous datasets, two microarray gene expression sets and one protein abundance set, applying a recently proposed feature selection method based on regularization. Results For each dataset we identified a signature that was successively evaluated both from the computational and functional characterization viewpoints, estimating the classification error and retrieving the most relevant biological knowledge from different repositories. Each signature includes genes already known to be related to AD and genes that are likely to be involved in the pathogenesis or in the disease progression. The integrated analysis revealed a meaningful overlap at the functional level. Conclusions The identification of three gene signatures showing a relevant overlap of pathways and ontologies, increases the likelihood of finding potential marker genes for AD.

  1. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine; Reinhard, Henrik; Zdunek, Dietmar

    2012-01-01

    Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria.......Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria....

  2. Effects of breed, gender, exercise and white-coat effect on markers of endothelial function in dogs

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Holte, A.V.; Mogensen, T.;

    2007-01-01

    This study examines how systemic biomarkers of endothelial function and nitric oxide metabolism are affected by exercise in dogs. Furthermore, breed variation and white-coat effect have been tested by sampling three different dog breeds both in their home and in a clinical setting. Short...... significantly higher when the sample was taken in the laboratory cf. at home, whereas ADMA and L-arginine were significantly lower. In conclusion, both short-term exercise and white-coat effect influence several plasma markers of endothelial function depending also on the breed and gender of the dogs......-term exercise increased plasma nitrate and nitrite (NOx) and von Willebrand factor (vWf). There was significant difference between Pointers and the small dog breeds Cairn Terriers and Cavalier King Charles Spaniels in the general plasma levels of vWf and asymmetric dimethylarginine (ADMA9. NOx and vWf were...

  3. Flow cytometric analyses of the viability, surface marker expression and function of lymphocytes from children following cryopreservation.

    Science.gov (United States)

    Chen, Xi; Zhang, Hui; Mou, Wenjun; Qi, Zhan; Ren, Xiaoya; Wang, Guoliang; Jiao, Hong; Kong, Xiaohui; Gui, Jingang

    2016-11-01

    Flow cytometric analysis is important for the investigation and clinical preparation of lymphocytes from children. However, the strict requirement of cell freshness and inter‑assay variability limits the application of this methodology for pediatric investigations. Therefore, it is necessary to identify a reliable cryopreservative method capable of maintaining high cell viability and proper cell function in lymphocytes from children. In the present study, eight commonly‑used cell cyropreservative methods were used, and their effects on cell viability, surface marker expression and cell function were examined. In addition, how these methods affect the distribution of T‑cell receptor Vβ subfamilies were also determined. The results of the present study provided valuable experimental evidence, based on which the optimal method for the cryopreservation of lymphocytes from children in pediatric investigations and clinical applications can be selected.

  4. Characterization of Myanmar Paw San Hmwe Accessions Using Functional Genetic Markers

    Directory of Open Access Journals (Sweden)

    Kyaw Swar Oo

    2015-03-01

    Full Text Available Paw San Hmwe (PSM rice has been cultivated in many areas of Myanmar for a long time. Strong aroma, good taste and its elongation during cooking are the key characteristics of PSM rice. Thirty-one PSM accessions were genotypically characterized, and their physical grain and cooking quality traits were studied. We used specific gene markers associated with aroma, apparent amylose content (AAC and alkali spreading value to determine the alleles carried by different PSM accessions. The results revealed that six PSM accessions (PSM10, PSM12, PSM13, PSM21, PSM22 and PSM30 had a 3-bp insertion in Os2AP gene. Gel consistency (GC allele was predominant among the PSM accessions for gelatinization temperature (GT, however, the phenotype observed was between low and intermediate GT because of the combination of the GC allele with the presence of low GT allele at heterozygous state from the other loci of the SSIIa gene. Intermediate to high AAC was observed among the PSM accessions corresponding to the haplotype identified for the single nucleotide polymorphism G/T and the (CTn repeat in the Wx gene. The characterization and grouping data of PSM accessions posted benefits to Myanmar seed banks, and our results will help in maintaining the integrity of PSM rice variety.

  5. Familial risk of psychosis as a function of putative organic etiology in psychotic probands: evaluation of a population-based sample.

    Science.gov (United States)

    Foley, D L; Walsh, D; Kendler, K S

    1996-02-16

    It is unresolved what, if any, characteristics should be used as a basis for assigning psychotic probands to different liability classes in high density family studies seeking to detect possible genetic linkage. Justification for any such assignments should ideally ensue from empirical evaluation of unselected samples. It has been suggested that the genetic liability of probands with an "organic" psychosis is lower than that found in "primary" cases. Should such cases be assigned differential liabilities in linkage analyses as one way of modeling etiologic heterogeneity? Utilizing data from a population-based family study conducted in County Roscommon in Western Ireland, we examined risk in the relatives of psychotic probands as a function of clinician ratings reflecting the probability that the proband's illness was organic. Contrary to expectation, risk was not significantly lower in relatives of probands whose illness was rated as organic by experienced clinicians. Attempts to identify possible phenocopies of psychosis with a lower familial liability in this treated epidemiologic sample were unsuccessful.

  6. Functional characterization of the gene FoOCH1 encoding a putative α-1,6-mannosyltransferase in Fusarium oxysporum f. sp. cubense.

    Science.gov (United States)

    Li, Min-Hui; Xie, Xiao-Ling; Lin, Xian-Feng; Shi, Jin-Xiu; Ding, Zhao-Jian; Ling, Jin-Feng; Xi, Ping-Gen; Zhou, Jia-Nuan; Leng, Yueqiang; Zhong, Shaobin; Jiang, Zi-De

    2014-04-01

    Fusarium oxysporum f. sp. cubense (FOC) is the causal agent of banana Fusarium wilt and has become one of the most destructive pathogens threatening the banana production worldwide. However, few genes related to morphogenesis and pathogenicity of this fungal pathogen have been functionally characterized. In this study, we identified and characterized the disrupted gene in a T-DNA insertional mutant (L953) of FOC with significantly reduced virulence on banana plants. The gene disrupted by T-DNA insertion in L953 harbors an open reading frame, which encodes a protein with homology to α-1,6-mannosyltransferase (OCH1) in fungi. The deletion mutants (ΔFoOCH1) of the OCH1 orthologue (FoOCH1) in FOC were impaired in fungal growth, exhibited brighter staining with fluorescein isothiocyanate (FITC)-Concanavalin A, had less cell wall proteins and secreted more proteins into liquid media than the wild type. Furthermore, the mutation or deletion of FoOCH1 led to loss of ability to penetrate cellophane membrane and decline in hyphal attachment and colonization as well as virulence to the banana host. The mutant phenotypes were fully restored by complementation with the wild type FoOCH1 gene. Our data provide a first evidence for the critical role of FoOCH1 in maintenance of cell wall integrity and virulence of F. oxysporum f. sp. cubense. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. In vivo subcellular localization of Mal de Rio Cuarto virus (MRCV) non-structural proteins in insect cells reveals their putative functions

    Energy Technology Data Exchange (ETDEWEB)

    Maroniche, Guillermo A.; Mongelli, Vanesa C.; Llauger, Gabriela; Alfonso, Victoria; Taboga, Oscar [Instituto de Biotecnologia, CICVyA, Instituto Nacional de Tecnologia Agropecuaria (IB-INTA), Las cabanas y Los Reseros s/n. Hurlingham Cp 1686, Buenos Aires (Argentina); Vas, Mariana del, E-mail: mdelvas@cnia.inta.gov.ar [Instituto de Biotecnologia, CICVyA, Instituto Nacional de Tecnologia Agropecuaria (IB-INTA), Las cabanas y Los Reseros s/n. Hurlingham Cp 1686, Buenos Aires (Argentina)

    2012-09-01

    The in vivo subcellular localization of Mal de Rio Cuarto virus (MRCV, Fijivirus, Reoviridae) non-structural proteins fused to GFP was analyzed by confocal microscopy. P5-1 showed a cytoplasmic vesicular-like distribution that was lost upon deleting its PDZ binding TKF motif, suggesting that P5-1 interacts with cellular PDZ proteins. P5-2 located at the nucleus and its nuclear import was affected by the deletion of its basic C-termini. P7-1 and P7-2 also entered the nucleus and therefore, along with P5-2, could function as regulators of host gene expression. P6 located in the cytoplasm and in perinuclear cloud-like inclusions, was driven to P9-1 viroplasm-like structures and co-localized with P7-2, P10 and {alpha}-tubulin, suggesting its involvement in viroplasm formation and viral intracellular movement. Finally, P9-2 was N-glycosylated and located at the plasma membrane in association with filopodia-like protrusions containing actin, suggesting a possible role in virus cell-to-cell movement and spread.

  8. Isolation and Characterization of Putative Probiotic Bacterial Strain, Bacillus amyloliquefaciens, from North East Himalayan Soil Based on In Vitro and In Vivo Functional Properties.

    Science.gov (United States)

    Hairul Islam, V I; Prakash Babu, N; Pandikumar, P; Ignacimuthu, S

    2011-12-01

    This study is aimed to isolate some novel probiotics from the soils of North East Himalayas. Eleven Gram positive isolates were obtained in MRS with Oxgall media from soil samples. Four of the isolates withstood the in vitro gastric juice pH 3.0 and 0.45% bile salt tolerance screening. Among these, PBT 3 showed high cell surface hydrophobicity and adhered to the Caco-2 cells. 16s rDNA gene sequences of this probiotic strains were identified as Bacillus amyloliquefaciens (accession no: JF836079). In in vivo bioefficacy evaluation by DSS-induced colitis animals, B. amyloliquefaciens significantly ameliorated the loss in body weight. Further, the treatment altered the levels of myeloperoxidase, lipoperoxides, and mucous content in the colon tissues compared with normal colon. It reduced the protein and mRNA levels of pro-inflammatory cytokines such as TNF-α and IL-1β. These biochemical findings were supported by histopathological evidences. Our study reports the use of B. amyloliquefaciens isolated from Himalayan soil as probiotic and its beneficial effect on IBD for the first time and suggests that this could be used as potential probiotics in functional foods or as a curative agent.

  9. Conserved residues within the putative S4-S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels.

    Science.gov (United States)

    Boukalova, Stepana; Marsakova, Lenka; Teisinger, Jan; Vlachova, Viktorie

    2010-12-31

    The vanilloid transient receptor potential channel TRPV1 is a tetrameric six-transmembrane segment (S1-S6) channel that can be synergistically activated by various proalgesic agents such as capsaicin, protons, heat, or highly depolarizing voltages, and also by 2-aminoethoxydiphenyl borate (2-APB), a common activator of the related thermally gated vanilloid TRP channels TRPV1, TRPV2, and TRPV3. In these channels, the conserved charged residues in the intracellular S4-S5 region have been proposed to constitute part of a voltage sensor that acts in concert with other stimuli to regulate channel activation. The molecular basis of this gating event is poorly understood. We mutated charged residues all along the S4 and the S4-S5 linker of TRPV1 and identified four potential voltage-sensing residues (Arg(557), Glu(570), Asp(576), and Arg(579)) that, when specifically mutated, altered the functionality of the channel with respect to voltage, capsaicin, heat, 2-APB, and/or their interactions in different ways. The nonfunctional charge-reversing mutations R557E and R579E were partially rescued by the charge-swapping mutations R557E/E570R and D576R/R579E, indicating that electrostatic interactions contribute to allosteric coupling between the voltage-, temperature- and capsaicin-dependent activation mechanisms. The mutant K571E was normal in all aspects of TRPV1 activation except for 2-APB, revealing the specific role of Lys(571) in chemical sensitivity. Surprisingly, substitutions at homologous residues in TRPV2 or TRPV3 had no effect on temperature- and 2-APB-induced activity. Thus, the charged residues in S4 and the S4-S5 linker contribute to voltage sensing in TRPV1 and, despite their highly conserved nature, regulate the temperature and chemical gating in the various TRPV channels in different ways.

  10. Inflammatory transcription factors as activation markers and functional readouts in immune-to-brain communication.

    Science.gov (United States)

    Rummel, Christoph

    2016-05-01

    Immune-to-brain communication pathways involve humoral mediators, including cytokines, central modulation by neuronal afferents and immune cell trafficking to the brain. During systemic inflammation these pathways contribute to mediating brain-controlled sickness symptoms including fever. Experimentally, activation of these signaling pathways can be mimicked and studied when injecting animals with pathogen associated molecular patterns (PAMPS). One central component of the brain inflammatory response, which leads, for example, to fever induction, is transcriptional activation of brain cells via cytokines and PAMPS. We and others have studied the spatiotemporal activation and the physiological significance of transcription factors for the induction of inflammation within the brain and the manifestation of fever. Evidence has revealed a role of nuclear factor (NF)κB in the initiation, signal transducer and activator of transcription (STAT)3 in the maintenance and NF-interleukin (IL)6 in the maintenance or even termination of brain-inflammation and fever. Moreover, psychological stressors, such as exposure to a novel environment, leads to increased body core temperature and genomic NF-IL6-activation, suggesting a potential use of NF-IL6-immunohistochemistry as a multimodal brain cell activation marker and a role for NF-IL6 for differential brain activity. In addition, the nutritional status, as reflected by circulating levels of the cytokine-like hormone leptin, influence immune-to-brain communication and age-dependent changes in LPS-induced fever. Overall, transcription factors remain therapeutically important targets for the treatment of brain-inflammation and fever induction during infectious/non-infectious inflammatory and psychological stress. However, the exact physiological role and significance of these transcription factors requires to be further investigated.

  11. A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

    Directory of Open Access Journals (Sweden)

    Beverly H Brummett

    Full Text Available Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys, is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366 and White women (N = 2,712 in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022 but not for men (p = .471. Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.

  12. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available BACKGROUND: When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. METHODOLOGY AND PRINCIPAL FINDINGS: In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294]. SIGNIFICANCE: Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  13. Neurobiological markers of exercise-related brain plasticity in older adults

    OpenAIRE

    Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Erin A Olson; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A; Pence, Brandt D.

    2012-01-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, ...

  14. Exploitation of sulfonylurea resistance marker and non-homologous end joining mutants for functional analysis in Zymoseptoria tritici.

    Science.gov (United States)

    Sidhu, Y S; Cairns, T C; Chaudhari, Y K; Usher, J; Talbot, N J; Studholme, D J; Csukai, M; Haynes, K

    2015-06-01

    The lack of techniques for rapid assembly of gene deletion vectors, paucity of selectable marker genes available for genetic manipulation and low frequency of homologous recombination are major constraints in construction of gene deletion mutants in Zymoseptoria tritici. To address these issues, we have constructed ternary vectors for Agrobacterium tumefaciens mediated transformation of Z. tritici, which enable the single step assembly of multiple fragments via yeast recombinational cloning. The sulfonylurea resistance gene, which is a mutated allele of the Magnaporthe oryzae ILV2 gene, was established as a new dominant selectable marker for Z. tritici. To increase the frequency of homologous recombination, we have constructed Z. tritici strains deficient in the non-homologous end joining pathway of DNA double stranded break repair by inactivating the KU70 and KU80 genes. Targeted gene deletion frequency increased to more than 85% in both Z. tritici ku70 and ku80 null strains, compared to ⩽10% seen in the wild type parental strain IPO323. The in vitro growth and in planta pathogenicity of the Z. tritici ku70 and ku80 null strains were comparable to strain IPO323. Together these molecular tools add significantly to the platform available for genomic analysis through targeted gene deletion or promoter replacements and will facilitate large-scale functional characterization projects in Z. tritici. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. ID1 Is a Functional Marker for Intestinal Stem and Progenitor Cells Required for Normal Response to Injury

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2014-11-01

    Full Text Available LGR5 and BMI1 mark intestinal stem cells in crypt base columnar cells and +4 position cells, respectively, but characterization of functional markers in these cell populations is limited. ID1 maintains the stem cell potential of embryonic, neural, and long-term repopulating hematopoietic stem cells. Here, we show in both human and mouse intestine that ID1 is expressed in cycling columnar cells, +4 position cells, and transit-amplifying cells in the crypt. Lineage tracing revealed ID1+ cells to be self-renewing, multipotent stem/progenitor cells that are responsible for the long-term renewal of the intestinal epithelium. Single ID1+ cells can generate long-lived organoids resembling mature intestinal epithelium. Complete knockout of Id1 or selective deletion of Id1 in intestinal epithelium or in LGR5+ stem cells sensitizes mice to chemical-induced colon injury. These experiments identify ID1 as a marker for intestinal stem/progenitor cells and demonstrate a role for ID1 in maintaining the potential for repair in response to colonic injury.

  16. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  17. Lactulose as a marker of intestinal barrier function in pigs after weaning

    NARCIS (Netherlands)

    Wijtten, P.J.A.; Verstijnen, J.J.; Kempen, van T.A.T.G.; Perdok, H.B.; Gort, G.; Verstegen, M.W.A.

    2011-01-01

    Intestinal barrier function in pigs after weaning is almost exclusively determined in terminal experiments with Ussing chambers. Alternatively, the recovery in urine of orally administered lactulose can be used to assess intestinal permeability in living animals. This experiment was designed to

  18. Lactulose as a marker of intestinal barrier function in pigs after weaning

    NARCIS (Netherlands)

    Wijtten, P.J.A.; Verstijnen, J.J.; Kempen, van T.A.T.G.; Perdok, H.B.; Gort, G.; Verstegen, M.W.A.

    2011-01-01

    Intestinal barrier function in pigs after weaning is almost exclusively determined in terminal experiments with Ussing chambers. Alternatively, the recovery in urine of orally administered lactulose can be used to assess intestinal permeability in living animals. This experiment was designed to stud

  19. Using functional genomics to identify molecular markers for fire blight resistance (Erwinia amylovora) in apple (Malus)

    Science.gov (United States)

    Fire blight, caused by Erwinia amylovora (Ea), is a destructive disease of apple (Malus), pear (Pyrus) and some woody ornamentals in the rose family (Rosaceae). The goal of this project is to use a functional genomics approach to develop tools to breed fire blight resistant apples. Six hundred fifty...

  20. Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation

    NARCIS (Netherlands)

    Broekmans, W.; Klopping-Ketelaars, I.A.A.; Bots, M.L.; Kluft, C.; Princen, H.; Hendriks, H.F.J.; Tijburg, L.B.M.; Poppel, van G.; Kardinaal, A.F.M.

    2004-01-01

    Background: Endothelial cell dysfunction may be related to an increase in cellular oxidative stress. Carotenoids and vitamins could have an antioxidant-mediated tempering influence on endothelial function and inflammation, thereby reducing the risk of atherosclerosis. Methods: We measured serum caro

  1. Small Molecule Cardiogenol C Upregulates Cardiac Markers and Induces Cardiac Functional Properties in Lineage-Committed Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Agnes K. Mike

    2014-01-01

    Full Text Available Background/Aims: Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Methods: Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC, and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Results: Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. Conclusion: CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  2. Independent influence of dietary protein on markers of kidney function and disease in obesity.

    Science.gov (United States)

    Friedman, Allon N; Yu, Zhangsheng; Juliar, Beth E; Nguyen, James T; Strother, Matthew; Quinney, Sara K; Li, Lang; Inman, Margaret; Gomez, Gerardo; Shihabi, Zak; Moe, Sharon

    2010-10-01

    Obesity is associated with glomerular hyperfiltration and increased urinary protein excretion, as well as structural and functional changes that lead to kidney disease and failure. Dietary protein mimics obesity's effects on the glomerular filtration rate (GFR) and proteinuria and, in certain circumstances, may have the potential to adversely affect kidney function. Here we tested the hypothesis that dietary protein independently explains elevations in the GFR and proteinuria found in obese persons with a normal serum creatinine. Seventeen patients were randomized in a double-blind, crossover fashion for 1-week periods to high (140 g/day) and low (50 g/day) protein diets with a 1-week washout interval separating these periods. High protein consumption was associated with a very modest but significant increase in the GFR of 5 ± 6 ml/min. Hence, while dietary protein does modulate kidney parameters, it is unlikely to fully account for the elevations in GFR and proteinuria found in obesity.

  3. Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

    Science.gov (United States)

    2016-10-01

    multiple domains of living and reduce emotional dysregulation and disinhibition associated with the co-occurring disorders . 15 Specific...Posttraumatic Stress Disorder (PTSD). TBI and PTSD are both characterized by deficits in multiple cognitive domains, including attention, executive function...provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently

  4. Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

    Science.gov (United States)

    2015-10-01

    retention of motor function.  Timeline. This paper was published in the Journal of Head Trauma Rehabilitation last year, it is attached to this...the neurobiology and neuropsychology associated with an evidence-based cognitive rehabilitation intervention will allow us to identify Veterans with...both TBI and PTSD who are predisposed to positive treatment outcomes. To our knowledge, this will be the first attempt to integrate neurobiological

  5. Gene Expression Profile in Delay Graft Function: Inflammatory Markers Are Associated with Recipient and Donor Risk Factors

    Directory of Open Access Journals (Sweden)

    Diego Guerrieri

    2014-01-01

    Full Text Available Background. Delayed graft function (DGF remains an important problem after kidney transplantation and reduced long-term graft survival of the transplanted organ. The aim of the present study was to determine if the development of DGF was associated with a specific pattern of inflammatory gene expression in expanded criteria of deceased donor kidney transplantation. Also, we explored the presence of correlations between DGF risk factors and the profile that was found. Methods. Seven days after kidney transplant, a cDNA microarray was performed on biopsies of graft from patients with and without DGF. Data was confirmed by real-time PCR. Correlations were performed between inflammatory gene expression and clinical risk factors. Results. From a total of 84 genes analyzed, 58 genes were upregulated while only 1 gene was downregulated in patients with DGF compared with no DGF (P=0.01. The most relevant genes fold changes observed was IFNA1, IL-10, IL-1F7, IL-1R1, HMOX-1, and TGF-β. The results were confirmed for IFNA1, IL-1R1, HMOX-1 and TGF-β. A correlation was observed between TGF-β, donor age, and preablation creatinine, but not body mass index (BMI. Also, TGF-β showed an association with recipient age, while IFNA1 correlated with recipient BMI. Furthermore, TGF-β, IFNA1 and HMOX-1 correlated with several posttransplant kidney function markers, such as diuresis, ultrasound Doppler, and glycemia. Conclusions. Overall, the present study shows that DGF is associated with inflammatory markers, which are correlated with donor and recipient DGF risk factors.

  6. Association of toxic and essential metals with atopy markers and ventilatory lung function in women and men

    Energy Technology Data Exchange (ETDEWEB)

    Pizent, Alica [Institute for Medical Research and Occupational Health, Zagreb (Croatia)], E-mail: apizent@imi.hr; Macan, Jelena; Jurasovic, Jasna; Varnai, Veda Marija; Milkovic-Kraus, Sanja; Kanceljak-Macan, Bozica [Institute for Medical Research and Occupational Health, Zagreb (Croatia)

    2008-02-15

    The association of age, smoking, alcohol, superoxide dismutase (SOD), glutathione peroxidase (GPx), blood lead (BPb) and cadmium (BCd) levels, and serum levels of copper (SCu), zinc (SZn) and selenium (SSe) with atopic status and ventilatory function was examined in the groups of 166 women and 50 men with no occupational exposure to metals or other xenobiotics. Markers of atopy included serum total IgE, skin prick test (SPT) to common inhalatory allergens, non-specific nasal reactivity (NNR) and non-specific bronchial reactivity (NBR). Parameters of ventilatory function included forced vital capacity (FVC) and forced expiratory volume in the first second (FEV{sub 1}). Significantly higher BPb, SZn, IgE and prevalence of positive SPT, and lower SCu and NNR was found in men than in women. Fifteen women taking female sex hormones (HT) had significantly higher SCu than women without HT. Regression models showed significant inverse associations between IgE and SCu (P = 0.021) and NNR and SCu (P = 0.044) in women. When excluding women with HT, the association of SCu and total IgE became of borderline significance (P = 0.051), association between SCu and NNR disappeared, and significant positive association between total IgE and BPb emerged (P = 0.046). In men, significant inverse association was found between positive SPT and SSe, and between NBR and SSe. A decrease in FVC% and FEV{sub 1}% was associated with an increase in smoking intensity (P < 0.001) and a decrease in SZn (P = 0.043 and P = 0.053, respectively). These results were observed at the levels of the metals comparable to those in general populations worldwide. The observed differences between men and women may partly be explained by different levels of relevant toxic and essential metals, and their combination. The role of female HT in associations of atopy markers and SCu should be further investigated.

  7. Evaluating the function of putative hormone transporters.

    Science.gov (United States)

    Frommer, Wolf B; Schulz, Burkhard; Murphy, Angus S

    2009-02-01

    Hormones typically serve as long distance signaling molecules. To reach their site of action, hormones need to be transported from the sites of synthesis. Many plant hormones are mobile, thus requiring specific transport systems for the export from their source cells as well as subsequent import into target cells. Hormone transport in general is still poorly understood. Auxin is probably the most intensively studied plant hormone concerning transport in the moment. To advance our understanding of hormone transport we need two principal data sets: information on the properties of the transport systems including substrate specificity and kinetics, and we need to identify candidate genes for the respective transporters. Physiological transport data can provide an important basis for identifying and characterizing candidate transporters and to define their in vivo role. A recent publication in Plant Physiology highlights how kinetic and specificity studies may help to identify cytokinin transporters.

  8. Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

    Institute of Scientific and Technical Information of China (English)

    Fang Hongbo; Liu Jing; Guo Dan; Liu Peixiang; Zhao Yongliang

    2014-01-01

    Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types.The hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI silencing.In this study,we used a methylation-specific PCR (MSP) method to evaluate the methylation status of the TGFBI promoter in human leukemias.Methods Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical samples.Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP method.Results Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines tested.Furthermore,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.Conclusion The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.

  9. No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy

    NARCIS (Netherlands)

    Myrup, B.; Jensen, T.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1997-01-01

    OBJECTIVE - The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DES

  10. Functionalization of Carbon Nanomaterial Surface by Doxorubicin and Antibodies to Tumor Markers

    Science.gov (United States)

    Perepelytsina, Olena M.; Yakymchuk, Olena M.; Sydorenko, Mychailo V.; Bakalinska, Olga N.; Bloisi, Francesco; Vicari, Luciano Rosario Maria

    2016-06-01

    The actual task of oncology is effective treatment of cancer while causing a minimum harm to the patient. The appearance of polymer nanomaterials and technologies launched new applications and approaches of delivery and release of anticancer drugs. The goal of work was to test ultra dispersed diamonds (UDDs) and onion-like carbon (OLCs) as new vehicles for delivery of antitumor drug (doxorubicin (DOX)) and specific antibodies to tumor receptors. Stable compounds of UDDs and OLCs with DOX were obtained. As results of work, an effectiveness of functionalization was 2.94 % w/ w for OLC-DOX and 2.98 % w/ w for UDD-DOX. Also, there was demonstrated that UDD-DOX and OLC-DOX constructs had dose-dependent cytotoxic effect on tumor cells in the presence of trypsin. The survival of adenocarcinoma cells reduced from 52 to 28 % in case of incubation with the UDD-DOX in concentrations from 8.4-2.5 to 670-20 μg/ml and from 72 to 30 % after incubation with OLC-DOX. Simultaneously, antibodies to epidermal growth factor maintained 75 % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus, the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs.

  11. Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo

    Institute of Scientific and Technical Information of China (English)

    PF Lalor; WK Lai; SM Curbishley; S Shetty; DH Adams

    2006-01-01

    The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are not simply barrier cells that restrict the access of bloodborne compounds to the parenchyma. They are functionally specialised endothelial cells that have complex roles, including not only receptor-mediated clearance of endotoxin, bacteria and other compounds, but also the regulation of inflammation, leukocyte recruitment and host immune responses to pathogens. Thus understandlng the differentiation and function of HSEC is critical for the elucidation of liver biology and pathophysiology. This article reviews methods for isolating and studying human hepatic endothelial cell populations using in vitro models. We also discuss the expression and functions of phenotypic markers, such as the presence of fenestrations and expression of VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells.

  12. Folic acid: a marker of endothelial function in type 2 diabetes?

    Directory of Open Access Journals (Sweden)

    Arduino A Mangoni

    2005-04-01

    Full Text Available Arduino A Mangoni1, Roy A Sherwood2, Belinda Asonganyi2, Emma L Ouldred3, Stephen Thomas4, Stephen HD Jackson31Department of Clinical Pharmacology, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, SA, Australia; 2Clinical Biochemistry, King’s College Hospital, London, UK; 3Department of Health Care of the Elderly, Guy’s, King’s, and St Thomas’ School of Medicine, King’s College, London, UK; 4Department of Diabetic Medicine, King’s College Hospital, London, UKObjectives: Endothelial dysfunction is a common feature of type 2 diabetes. Recent studies suggest that the B-vitamin folic acid exerts direct beneficial effects on endothelial function, beyond the well known homocysteine lowering effects. Therefore, folic acid might represent a novel “biomarker” of endothelial function. We sought to determine whether plasma levels of folic acid determine endothelial-dependent vasodilation in patients with type 2 diabetes.Methods: Forearm arterial blood flow (FABF was measured at baseline and during intrabrachial infusion of the endothelial-dependent vasodilator acetylcholine (15 µg/min and the endothelial-independent vasodilator sodium nitroprusside (2 µg/min in 26 type 2 diabetic patients (age 56.5 ± 0.9 years, means ± SEM with no history of cardiovascular disease.Results: FABF ratio (ie, the ratio between the infused and control forearm FABF significantly increased during acetylcholine (1.10 ± 0.04 vs 1.52 ± 0.07, p < 0.001 and sodium nitroprusside (1.12 ± 0.11 vs 1.62 ± 0.06, p < 0.001 infusions. After correcting for age, gender, diabetes duration, smoking, hypertension, body mass index, microalbuminuria, glycated hemoglobin, low-density lipoprotein cholesterol, and homocysteine, multiple regression analysis showed that plasma folic acid concentration was the only independent determinant (p = 0.037, R2 = 0.22 of acetylcholine-mediated, but not sodium nitroprusside-mediated, vasodilatation

  13. BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study

    DEFF Research Database (Denmark)

    Komulainen, P.; Pedersen, Maria; Hanninen, T.

    2008-01-01

    (+/-SEM) plasma BDNF level than men (1721+/-55vs. 1495+/-54pg/ml, PMemory by 56% (95% CI 1.......08-2.26, P=0.019), in Word List Recall by 50% (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99, P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data were adjusted for age, education, depression, impaired glucose metabolism, cardiovascular disease......, antihypertensive medication, lipid lowering medication, use of sex hormones, smoking, alcohol consumption, storing time of plasma in the freezer and platelet count. BDNF was not associated with cognition in men. Present data suggest that plasma BDNF is a biomarker of impaired memory and general cognitive function...

  14. The Effect of Krill Oil Supplementation on Exercise Performance and Markers of Immune Function.

    Directory of Open Access Journals (Sweden)

    Mariasole Da Boit

    Full Text Available Krill oil is a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFAs, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, which may alter immune function after exercise. The aim of the study was to determine the effects of krill oil supplementation on post exercise immune function and performance.Nineteen males and 18 females (age: 25.8 ± 5.3 years; mean ± S.D. were randomly assigned to 2 g/day of krill oil (n = 18 or placebo (n = 19 supplementation for 6 weeks. A maximal incremental exercise test and cycling time trial (time to complete set amount of work were performed pre-supplementation with the time trial repeated post-supplementation. Blood samples collected pre- and post- supplementation at rest, and immediately, 1 and 3h post-exercise. Plasma IL-6 and thiobarbituric acid reactive substances (TBARS concentrations and, erythrocyte fatty acid composition were measured. Natural killer (NK cell cytotoxic activity and peripheral blood mononuclear cell (PBMC IL-2, IL-4, IL-10, IL-17 and IFNγ production were also measured.No effects of gender were noted for any variable. PBMC IL-2 and NK cell cytotoxic activity were greater (P < 0.05 3h post exercise in the krill oil compared to the control group. Plasma IL-6 and TBARS, PBMC IL-4, IL-10, IL-17 and IFNγ production, along with performance and physiological measures during exercise, were not different between groups.Six weeks of krill oil supplementation can increase PBMC IL-2 production and NK cell cytotoxic activity 3h post-exercise in both healthy young males and females. Krill oil does not modify exercise performance.

  15. Clinical Usefulness of Serum Cystatin C as a Marker of Renal Function

    Directory of Open Access Journals (Sweden)

    Kwang-Sook Woo

    2014-08-01

    Full Text Available BackgroundAccurate renal function measurements are important in the diagnosis and treatment of kidney diseases. In contrast to creatinine, the production of serum cystatin C has been extensively reported to be unaffected by body muscle mass, age, gender, and nutritional status.MethodsOur study included 37 samples from diabetic chronic kidney disease (CKD patients for whom serum creatinine tests had been requested and 40 samples from a healthy populations in Dong-A University Hospital between May 2010 and June 2010. The assay precision (i.e., the coefficient of variation and the reference range of the serum cystatin C test were evaluated. We compared the estimated glomerular filtration rates (GFRs based on cystatin C with those based on creatinine. Moreover, we investigated the influences of age, gender, weight, and muscle mass on serum creatinine and serum cystatin C.ResultsThere was a positive correlation between GFR based on creatinine and that based on cystatin C (r=0.79, P<0.0001 among the diabetic CKD patients. Serum creatinine and cystatin C were significantly correlated with body weight and muscle mass, but the strengths of these correlations were greater for serum creatinine. The precision study revealed excellent results for both the high and low controls. The 95% reference interval of cystatin C in the healthy population was 0.371 to 1.236 mg/L.ConclusionBased on these results, we conclude that, despite the strong correlation between serum creatinine and cystatin C, cystatin C is less affected by weight and muscle mass and might represent a better alternative for the assessment of renal function.

  16. Functional clustering and lineage markers: insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations.

    Science.gov (United States)

    Hume, David A; Summers, Kim M; Raza, Sobia; Baillie, J Kenneth; Freeman, Thomas C

    2010-06-01

    Very large microarray datasets showing gene expression across multiple tissues and cell populations provide a window on the transcriptional networks that underpin the differences in functional activity between biological systems. Clusters of co-expressed genes provide lineage markers, candidate regulators of cell function and, by applying the principle of guilt by association, candidate functions for genes of currently unknown function. We have analysed a dataset comprising pure cell populations from hemopoietic and non-hemopoietic cell types (http://biogps.gnf.org). Using a novel network visualisation and clustering approach, we demonstrate that it is possible to identify very tight expression signatures associated specifically with embryonic stem cells, mesenchymal cells and hematopoietic lineages. Selected examples validate the prediction that gene function can be inferred by co-expression. One expression cluster was enriched in phagocytes, which, alongside endosome-lysosome constituents, contains genes that may make up a 'pathway' for phagocyte differentiation. Promoters of these genes are enriched for binding sites for the ETS/PU.1 and MITF families. Another cluster was associated with the production of a specific extracellular matrix, with high levels of gene expression shared by cells of mesenchymal origin (fibroblasts, adipocytes, osteoblasts and myoblasts). We discuss the limitations placed upon such data by the presence of alternative promoters with distinct tissue specificity within many protein-coding genes.

  17. Neurophysiological marker of inhibition distinguishes language groups on a non-linguistic executive function test.

    Science.gov (United States)

    Fernandez, M; Tartar, J L; Padron, D; Acosta, J

    2013-12-01

    Successful interaction with the environment depends on flexible behaviors which require shifting attention, inhibiting primed responses, ignoring distracting information, and withholding motor responses. These abilities, termed executive function (EF), are believed to be mediated by inhibitory processes in the frontal lobes. Superior performance on EF tests (i.e., faster reaction times (RT), and fewer errors) has been shown in bilinguals compared to monolingual speakers. However, findings are inconsistent, and no study has directly linked this bilingual advantage to frontal lobe inhibitory processes. To clarify this uncertainty, we concomitantly tested neural inhibitory processes and behavioral responses on an EF test in bilinguals and monolinguals. Specifically, we compared English monolinguals (N=15) to Spanish/English bilinguals (N=13) on event-related brain potentials (ERP) during a non-linguistic, auditory Go/NoGo task, a task linked to non-motor, cognitive inhibition in monolinguals. Participants responded with a button press on trials in which target tone-pairs (Go trials) were presented and withheld their responses on non-target trials (NoGo trials). Results revealed significantly greater inhibition (i.e., greater mean N2 amplitude) in bilinguals compared to monolinguals during NoGo trials even though both groups performed the task equally well (i.e., withheld a motor response). On Go trials where participants pressed a response button, neither ERPs nor RT distinguished the groups. Additionally, scores on a second language proficiency test (i.e., English in our bilingual group) were positively correlated with N2 amplitude. These findings are the first to directly link this bilingual advantage to a neural correlate of inhibition and to reveal that inhibition in bilinguals is moderated by second language proficiency. Results are discussed in the context of plasticity, and we propose that evaluating bilinguals at varying levels of second-language proficiency

  18. Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Giordano, A. [Department of Nuclear Medicine, Catholic University of the Sacred Heart, Rome (Italy); Calcagni, M.L. [Department of Nuclear Medicine, Catholic University of the Sacred Heart, Rome (Italy); Rossi, B. [Department of Nuclear Medicine, Catholic University of the Sacred Heart, Rome (Italy); Fuso, L. [Department of Respiratory Physiology, Catholic University of the Sacred Heart, Rome (Italy); Accardo, D. [Department of Respiratory Physiology, Catholic University of the Sacred Heart, Rome (Italy); Valente, S. [Department of Respiratory Physiology, Catholic University of the Sacred Heart, Rome (Italy); Pistelli, R. [Department of Respiratory Physiology, Catholic University of the Sacred Heart, Rome (Italy); Franceschini, R. [Sorin Biomedica, Saluggia (Italy); Troncone, L. [Department of Nuclear Medicine, Catholic University of the Sacred Heart, Rome (Italy)

    1997-01-01

    In this study we performed: (1) a chromatographic study of nebulized {sup 123}I-MIBG; (2) a quantitative evaluation of the lung distribution of {sup 123}I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid ({sup 99m}Tc-DTPA) and (3) an assessment of {sup 123}I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with {sup 99m}Tc-DTPA. For these purposes, eight normal subjects were divided randomly into an ``MIBG group`` and a ``DTPA group`` (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized {sup 123}I-MIBG ranged between 97.18% and 98.70%. The lung distribution of {sup 123}I-MIBG, as judged by the aerosol penetration index, was identical to that of {sup 99m}Tc-DTPA under all study conditions. The {sup 123}I-MIBG clearance rate was slower than that of {sup 99m}Tc-DTPA under baseline conditions (135{+-}32 min vs 69{+-}27 min, P<0.01) and increased significantly after propranolol administrations, while the {sup 99m}Tc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of {sup 123}I-MIBG; (2) the lung distribution of {sup 123}I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of {sup 123}I-MIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use. (orig.). With 2 figs., 3 tabs.

  19. Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Danza Francesco

    2005-08-01

    Full Text Available Abstract Background A progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients. Methods 100 SSc patients (76 with limited and 24 with diffuse disease underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs every 6–12 months, echocardiography, high resolution computed tomography (HRCT and bronchoalveolar lavage (BAL, if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices. Results 90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5% patients, with 55 (59.1% showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1% revealed alveolitis. 12 (75% of these patients had restrictive lung disease (p 14 (OR(95%CIs:7.03(1.40–34.33. The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001 and with the skin score (r = 0.33, p = 0.001. Cultures of BAL fluid resulted positive in 10 (23.8% of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80% of these patients (p = 0.01. Pulmonary artery systolic pressure ≥ 40 mmHg was found in 6 (37.5% patients with alveolitis. Conclusion We found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL

  20. Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis.

    Science.gov (United States)

    De Santis, Maria; Bosello, Silvia; La Torre, Giuseppe; Capuano, Anna; Tolusso, Barbara; Pagliari, Gabriella; Pistelli, Riccardo; Danza, Francesco Maria; Zoli, Angelo; Ferraccioli, Gianfranco

    2005-08-17

    A progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients. 100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6-12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices. 90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p 14 (OR(95%CIs):7.03(1.40-34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure > or = 40 mmHg was found in 6 (37.5%) patients with alveolitis. We found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL would be necessary to detect any infections of the

  1.  Is serum cystatin C a better marker of kidney function than serum creatinine in septic newborns?

    Directory of Open Access Journals (Sweden)

    Iwona Maruniak-Chudek

    2012-04-01

    Full Text Available [sub][/sub] Introduction:Several studies have claimed that the estimation of serum cystatin C could be a better marker of kidney excretory function than serum creatinine. However, its role in the diagnosis of reduced kidney function was not unquestionably confirmed. The aim of this study was to analyze the concentrations of serum cystatin C in neonates with sepsis.Material/Methods:Thirty-two neonates (gestational age from 34 to 40 weeks admitted to the NICU during the first 14 days of life were enrolled. Serum cystatin C concentrations were estimated by ELISA during three successive days in neonates treated for infection. The study group consisted of 9 newborns with sepsis, 14 with severe sepsis and 9 with septic shock.Results/Discussion:At the beginning of the observational period the mean serum concentration of cystatin C in the study group was 1.35 mg/L (95�0CI 1.20–1.49. Surprisingly, the lowest concentration of cystatin was observed in patients with septic shock (1.23 mg/L; 95 0.92–1.54 within the observation period. Higher concentrations were found in neonates with sepsis (1.47 mg/L; 95 1.04–1.90 and severe sepsis (1.50; 1.12–1.87. There was no correlation between serum cystatin C concentration and serum creatinine or gestational age.A significant correlation was discovered between chronological age and cystatin C (R=–0.439, p=0.01. There was a tendency for cystatin C to decline during the second observational day in patients with sepsis (to 1.53 mg/L; 95: 1.19–1.86 and severe sepsis (to 1.32 mg/L; 95: 1.07–1.57, while a slight insignificant increase in patient with septic shock (to 1.28 mg/L; 95: 0.88–1.68 was revealed. The interrelation between age and cystatin C concentration disappeared in the following days of stay in the NICU. Even in patients who died in the course of septic shock the observed changes in cystatin C levels were small and did not exceed those of serum creatinine.Conclusions:Cystatin C is not a

  2. Molecular and functional diversity of PGPR fluorescent Pseudomonads based on 16S rDNA-RFLP and RAPD markers.

    Science.gov (United States)

    Singh, Bhim Pratap

    2015-09-01

    The genetic and functional diversity of plant growth promoting rhizobacterial (PGPR) fluorescent pseudomonads associated with chickpea (Cicer arietinum L.) rhizosphere was analyzed. In total, 34 isolates along with two reference isolates were screened for various plant growth promoting traits (phosphorous solubilization, ACC deaminase, HCN, IAA and siderophore productions) and antagonist activity against four fungal phytopathogens and three bacterial pathogens. Most of the isolates, that showed PGPR activity, also showed antagonistic activity against all the three fungal pathogens. The genetic relationship was assessed by using random amplification of polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (16S rDNA-RFLP). Relationship between both the markers was analyzed based on mantel test and a negative correlation was observed. The study concluded that PGPR traits appeared to be strain specific rather than specific to any phylogenetic group. The study also reported that 16S rDNA based profiling differentiated PGPR fluorescent Pseudomonas on the basis of location rather than biological trait. RAPD profiling could be useful to differentiate among the closely related isolates. The genetic and functional diversity of fluorescent pseudomonads, associated with the chickpea rhizosphere, has useful ecological role and potential utilization in sustainable agriculture.

  3. Does Functional Connectivity Provide a Marker for Cognitive Rehabilitation Effects in Alzheimer’s Disease? An Interventional Study

    Science.gov (United States)

    Ochmann, Sina; Dyrba, Martin; Grothe, Michel J.; Kasper, Elisabeth; Webel, Steffi; Hauenstein, Karlheinz; Teipel, Stefan J.

    2017-01-01

    Background: Cognitive rehabilitation (CR) is a cognitive intervention for patients with Alzheimer’s disease (AD) that aims to maintain everyday competences. The analysis of functional connectivity (FC) in resting-state functional MRI has been used to investigate the effects of cognitive interventions. Objectives: We evaluated the effect of CR on the default mode network FC in a group of patients with mild AD, compared to an active control group. Methods: We performed a three-month interventional study including 16 patients with a diagnosis of AD. The intervention group (IG) consisted of eight patients, performing twelve sessions of CR. The active control group (CG) performed a standardized cognitive training. We used a seed region placed in the posterior cingulate cortex (PCC) for FC analysis, comparing scans acquired before and after the intervention. Effects were thresholded at a significance of p < 0.001 (uncorrected) and a minimal cluster size of 50 voxels. Results: The interaction of group by time showed a higher increase of PCC connectivity in IG compared to CG in the bilateral cerebellar cortex. CG revealed widespread, smaller clusters of higher FC increase compared with IG. Across all participants, an increase in quality of life was associated with connectivity increase over time in the bilateral precuneus. Conclusions: CR showed an effect on the FC of the DMN in the IG. These effects need further study in larger samples to confirm if FC analysis may suit as a surrogate marker for the effect of cognitive interventions in AD. PMID:28372326

  4. GLUCOSE METABOLITE PATTERNS AS MARKERS OF FUNCTIONAL DIFFERENTIATION IN FRESHLY ISOLATED AND CULTURED MOUSE MAMMARY EPITHELIAL CELLS

    Energy Technology Data Exchange (ETDEWEB)

    Emerman, J.T.; Bartley, J.C.; Bissell, M.J.

    1980-06-01

    In the mammary gland of nonruminant animals, glucose is utilized in a characteristic and unique way during lactation. We have measured the incorporation of glucose carbon from [U-{sup 14}C] glucose into intermediary metabolites and metabolic products in mammary epithelial cells from virgin, pregnant, and lactating mice and demonstrate that glucose metabolite patterns can be used to recognize stages of differentiated function. For these cells, the rates of synthesis of glycogen and lactose, the ratio of lactate to alanine, and the ratio of citrate to malate were important parameters in identifying the degree of expression of differentiation. We further show that these patterns can be used as markers to determine the differentiated state of cultured mammary epithelial cells. Cells maintained on plastic substrates lose their distinctive glucose metabolite patterns while those on floating collagen gels do not. Cells from pregnant mice have a pattern similar to freshly isolated cells from pregnant mice. The pattern of cells from lactating mice is different from that of the cells of origin, and resembles that of the cells from pregnant mice. Our findings suggest that the floating collagen gels under the culture conditions used in these experiments provide an environment for the functional expression of the pregnant state, while additional factors are needed for the expression of the lactating state.

  5. Influence of the conserved disulphide bond, exposed to the putative binding pocket, on the structure and function of the immunoglobulin-like molecular chaperone Caf1M of Yersinia pestis.

    Science.gov (United States)

    Zav'yalov, V P; Chernovskaya, T V; Chapman, D A; Karlyshev, A V; MacIntyre, S; Zavialov, A V; Vasiliev, A M; Denesyuk, A I; Zav'yalova, G A; Dudich, I V; Korpela, T; Abramov, V M

    1997-06-01

    The Yersinia pestis protein Caf1M is a typical representative of a subfamily of periplasmic molecular chaperones with characteristic structural and functional features, one of which is the location of two conserved cysteine residues close to the putative binding pocket. We show that these residues form a disulphide bond, the reduction and alkylation of which significantly increases the dissociation constant of the Caf1M-Caf1 (where Caf 1 is a polypeptide subunit of the capsule) complex [from a Kd of (4.77+/-0.50)x10(-9) M for the intact protein to one of (3.68+/-0.68)x10(-8) M for the modified protein]. The importance of the disulphide bond for the formation of functional Caf1M in vivo was demonstrated using an Escherichia coli dsbA mutant carrying the Y. pestis f1 operon. In accordance with the CD and fluorescence measurements, the disulphide bond is not important for maintenance of the overall structure of the Caf1M molecule, but would appear to affect the fine structural properties of the subunit binding site. A three-dimensional model of the Caf1M-Caf1 complex was designed based on the published crystal structure of PapD (a chaperone required for Pap pili assembly) complexed with a peptide corresponding to the C-terminus of the papG subunit. In the model the disulphide bond is in close proximity to the invariant Caf1M Arg-23 and Lys-142 residues that are assumed to anchor the C-terminal group of the subunit. The importance of this characteristic disulphide bond for the orchestration of the binding site and subunit binding, as well as for the folding of the protein in vivo, is likely to be a common feature of this subfamily of Caf1M-like chaperones. A possible model for the role of the disulphide bond in Caf1 assembly is discussed.

  6. Marker development

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  7. Effect of Piper betle on cardiac function, marker enzymes, and oxidative stress in isoproterenol-induced cardiotoxicity in rats.

    Science.gov (United States)

    Arya, Dharamvir Singh; Arora, Sachin; Malik, Salma; Nepal, Saroj; Kumari, Santosh; Ojha, Shreesh

    2010-11-01

    The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300 mg/kg) and P. betle (75, 150, and 300 mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300 mg/kg) or saline was orally administered for 30 days. ISP (85 mg/kg, s.c.) was administered at an interval of 24 h on the 28(th) and 29(th) day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (-LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (-LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300 mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.

  8. Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis.

    Science.gov (United States)

    White, Helen; Shaw, Nicola; Denman, Sarah; Pollard, Kim; Wynne, Sarah; Peckham, Daniel Gavin

    2017-03-01

    The aim of this study was to characterise adherence in an adult population with cystic fibrosis (CF) and to investigate if variation in lung function was a predictor of adherence to treatment.The adherence of patients aged ≥16 years from an adult CF centre was measured by medication possession ratio (MPR) and self-report. Patients were assigned to one of three adherence categories (coefficient variation measures for forced expiratory volume in 1 s (FEV1), weight and C-reactive protein concentration, measured from 6 months and 12 months before baseline.MPR data for 106 of 249 patients (mean age 29.8±9.2 years) was retrieved, indicating a mean adherence of 63%. The coefficient of variation for FEV1 was inversely related to adherence and was a univariate predictor of adherence (6 months: OR 0.92, 95% CI 0.87-0.98, p=0.005; 12 months: OR 0.94, 95% CI 0.93-0.99, p=0.03) and remained significant in the final models. The coefficient of variation of weight and C-reactive protein were not predictive of adherence.The coefficient of variation of FEV1 was identified as an objective predictor of adherence. Further evaluation of this potential marker of adherence is now required. Copyright ©ERS 2017.

  9. Responses of bacterial community and functional marker genes of nitrogen cycling to biochar, compost and combined amendments in soil.

    Science.gov (United States)

    Wu, Haipeng; Zeng, Guangming; Liang, Jie; Chen, Jin; Xu, Jijun; Dai, Juan; Li, Xiaodong; Chen, Ming; Xu, Piao; Zhou, Yaoyu; Li, Fei; Hu, Liang; Wan, Jia

    2016-10-01

    Biochar and compost are seen as two attractive waste management options and are used for soil amendment and pollution remediation. The interaction between biochar and composting may improve the potential benefits of biochar and compost. We investigated soil physicochemical properties, bacterial community, bacterial 16S rRNA, and functional marker genes of nitrogen cycling of the soil remedied with nothing (S), compost (SC), biochar (SB), a mixture of compost and biochar (SBC), composted biochar (SBced), and a composted mixture of biochar and biomass (SBCing). The results were that all amendments (1) increased the bacterial community richness (except SB) and SBCing showed the greatest efficiency; (2) increased the bacterial community diversity (SBCing > SBC > SC > SBced > SB > S); and (3) changed the gene copy numbers of 16S rRNA, nirK, nirS, and nosZ genes of bacteria, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB). All amendments (except SB) could increase the gene copy number of 16S rRNA, and SBCing had the greatest efficiency. The changes of soil bacterial community richness and diversity and the gene copy numbers of 16S rRNA, nirK, nirS, nosZ, AOA, and AOB would affect carbon and nitrogen cycling of the ecosystem and also implied that BCing had the greatest efficiency on soil amendment.

  10. [Evaluation of some selected structural and functional parameters of red blood cells as oxidative stress markers in elderly people].

    Science.gov (United States)

    Kujawski, K; Kedziora-Kornatowska, K; Koter, M; Duchnowicz, P; Rysz, J; Markuszewski, L; Błaszczak, R; Kornatowski, T; Grześk, G; Kedziora, J; Olszewski, R

    2005-12-01

    The ageing process induces age-related involutionary changes and leads to increased occurrence of many diseases. One of the most important theories of ageing and development of many pathologies is the free radical theory, which assumes that ageing process leads to lost of oxidative balance. of the research was to evaluate the degree of membrane lipid peroxidation, internal microviscosity, activity of membrane ATPase, both total and Na(+)K(+)-dependent, and markers of oxidative damage in erythrocyte membrane protein in elderly people. The examination was performed on 35 people. The examined group (15 persons, mean age 71,3) consisted of healthy elderly people. The reference group was formed with younger healthy people (20 persons, mean age 55). Erythrocyte membrane lipid peroxidation was found stronger in the group of elderly people. Erythrocyte internal microviscosity was significantly higher in the elderly. The activity of ATPase, both total and Na(+)K(+)-dependent, appeared remarkably greater in the group of younger people. Stronger membrane lipid damage was observed in older age group, which may be implied by lower--SH group concentration, and higher W/S parameter value. The obtained results reveal that in elderly people the intensification of oxidative stress in the entire body occurs, which may be confirmed by structural and functional oxidative erythrocyte damage. This conclusion may be significant for pathogenesis of many diseases in this period of life.

  11. A single-step enzyme immunoassay capillary sensor composed of functional multilayer coatings for the diagnosis of marker proteins.

    Science.gov (United States)

    Funano, Shun-ichi; Sugahara, Masato; Henares, Terence G; Sueyoshi, Kenji; Endo, Tatsuro; Hisamoto, Hideaki

    2015-03-07

    A single-step, easy-to-use enzyme immunoassay capillary sensor, composed of functional multilayer coatings, was developed in this study. The coatings were composed of substrate-immobilized hydrophobic coating, hydrogel coating, and soluble coating containing an enzyme-labeled antibody. The response mechanism involved a spontaneous immunoreaction triggered by capillary action-mediated introduction of a sample antigen solution and subsequent separation of unreacted enzyme-labeled antibodies and antigen-enzyme-labeled antibody complexes by the molecular sieving effect of the hydrogel. An enzyme reaction at the substrate-immobilized hydrophobic coating/hydrogel coating interface resulted in a protein-selective fluorescence response. An antigen concentration-dependent response was obtained for diagnostic marker protein samples (hemoglobin A1c (HbA1c), 7.14-16.7 mg mL(-1); alpha-fetoprotein (AFP), 1.4-140 ng mL(-1); C-reactive protein (CRP), 0.5-10 μg mL(-1)) that cover a clinically important concentration range. The successful measurement of CRP in diluted serum samples demonstrated the application of this capillary sensor.

  12. Association between endothelial and platelet function markers and adiponectin in renal transplanted recipients on cyclosporine and tacrolimus immunosuppression based therapy.

    Science.gov (United States)

    Sahin, Garip; Akay, Olga Meltem; Uslu, Sema; Bal, Cengiz; Yalcin, Ahmet Ugur; Gulbas, Zafer

    2015-06-01

    Coagulation abnormalities, endothelial dysfunction and arteriosclerosis play a key role in cardiovascular disease state observed in transplanted patients. Plasma adiponectin levels are lower following kidney transplantation. However, there is still a debate about this topic in the literature. This study evaluated, adiponectin levels associated with markers of endothelial dysfunction and platelet function in renal transplant patients. Sixty-six renal transplant patients were studied. Patients were grouped according to immunosuppression regimen. Group 1 (n = 36) were treated with cyclosporine A based regimes and group 2 (n = 30) were treated with tacrolimus based regimes. Plasma adiponectin, asymmetric dimethyl arginine (ADMA), sP-selectin levels and platelet aggregation tests were studied and were compared with those in control group (n = 15, group 3). Adiponectin, sP-selectin and ADMA levels were higher in group 1 and statistically significant differences were observed compared with those of group 2 and group 3, respectively (P  0.05). Adiponectin levels are elevated in line with ADMA and sP-selectin levels. Since CsA induces higher adiponectin levels, platelet activation and endothelial dysfunction. These changes may be responsible for the increased risk of post-transplant cardiovascular events in renal transplant patients. © 2015 Asian Pacific Society of Nephrology.

  13. A combined functional and structural genomics approach identified an EST-SSR marker with complete linkage to the Ligon lintless-2 genetic locus in cotton (Gossypium hirsutum L.

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    Tang Yuhong

    2011-09-01

    Full Text Available Abstract Background Cotton fiber length is an important quality attribute to the textile industry and longer fibers can be more efficiently spun into yarns to produce superior fabrics. There is typically a negative correlation between yield and fiber quality traits such as length. An understanding of the regulatory mechanisms controlling fiber length can potentially provide a valuable tool for cotton breeders to improve fiber length while maintaining high yields. The cotton (Gossypium hirsutum L. fiber mutation Ligon lintless-2 is controlled by a single dominant gene (Li2 that results in significantly shorter fibers than a wild-type. In a near-isogenic state with a wild-type cotton line, Li2 is a model system with which to study fiber elongation. Results Two near-isogenic lines of Ligon lintless-2 (Li2 cotton, one mutant and one wild-type, were developed through five generations of backcrosses (BC5. An F2 population was developed from a cross between the two Li2 near-isogenic lines and used to develop a linkage map of the Li2 locus on chromosome 18. Five simple sequence repeat (SSR markers were closely mapped around the Li2 locus region with two of the markers flanking the Li2 locus at 0.87 and 0.52 centimorgan. No apparent differences in fiber initiation and early fiber elongation were observed between the mutant ovules and the wild-type ones. Gene expression profiling using microarrays suggested roles of reactive oxygen species (ROS homeostasis and cytokinin regulation in the Li2 mutant phenotype. Microarray gene expression data led to successful identification of an EST-SSR marker (NAU3991 that displayed complete linkage to the Li2 locus. Conclusions In the field of cotton genomics, we report the first successful conversion of gene expression data into an SSR marker that is associated with a genomic region harboring a gene responsible for a fiber trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the Li2 locus on

  14. Effects of exposure to biomass burning on pulmonary inflammatory markers and pulmonary function in individuals with COPD.

    Science.gov (United States)

    Ramos, D; Proença, M; Leite, M R; Ferreira, A D; Trevisan, I B; Brígida, G F S; Tacao, G Y; Ramos, E M C

    2017-06-15

    Pulmonary rehabilitation (PR) has many benefits for individuals with COPD. However, it is not clear whether PR could prevent the hazards of air pollution exposure. This study aimed to analyze the effects of biomass burning exposure on pulmonary inflammatory markers and pulmonary function in individuals with COPD, participants and non-participants of PR. 35 subjects were divided into three groups: individuals with COPD who received PR (G1, n=15), those who did not (G2, n=10), and a control group composed of healthy individuals without COPD (CG, n=10). Measurements of lung function and concentrations of IL-6, IL-10, and TNF-α in exhaled breath condensate samples were collected. The assessment and concentrations of particulate matter (PM10), nitrogen dioxide (NO2), ozone (O3), temperature (T), and relative air humidity (RAH) were recorded in biomass burning and non-burning periods. There was a significant increase in the concentrations of air pollutants in the biomass burning period. In this period, an increase in IL-6 (G1p=0.041, G2 p=.012), and a reduction in the FEV1/FVC ratio (G1p=0.021, G2 p=.007) were observed in individuals with COPD. In G1, the increase in IL-6 concentrations correlated positively with O3 (r=0.693; p=.006), and negatively with RAH (r=-0.773; p=.003) in the burning period. Individuals with COPD exposed to biomass burning demonstrated increased pulmonary inflammation and a reduction in the FEV1/FVC ratio, regardless of their engagement in PR. Copyright © 2017. Published by Elsevier España, S.L.U.

  15. FUNCIONES DEL MARCADOR DISCURSIVO PUES EN EL HABLA DE MEDELLÍN, COLOMBIA FUNCTIONS OF THE DISCOURSE MARKER PUES IN THE SPEECH OF MEDELLÍN, COLOMBIA

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    Róbinson Grajales Alzate

    2011-06-01

    Full Text Available En la actualidad las investigaciones sobre los marcadores discursivos se centran, más que en su clasificación, en la descripción de marcadores en particular o grupos de ellos. En este trabajo se define para cada una de las funciones del marcador discursivo pues su significado semántico-pragmático y su frecuencia de aparición. Para esta descripción se tomaron como base otras investigaciones sobre este marcador con el fin establecer las funciones que se han encontrado en la literatura especializada y usarlas como referencia para el análisis. La muestra de las ocurrencias del marcador discursivo pues se tomó del corpus PRESEEA-Medellín. Se encontraron siete funciones para este marcador en dicha comunidad de habla, de las cuales una no estaba registrada en la literatura revisada, lo cual contribuye a ampliar la descripción de este marcador en el español general y abre nuevas posibilidades para continuar la investigación del uso del marcador discursivo pues.Current research on discourse markers centers on the description of particular markers or groups of markers, rather than on their classification. This article defines the semantic-pragmatic meaning and the frequency of occurrence for each one of the functions of the discourse marker pues. This description took into account other research on this marker in order to establish the functions found in the specialized literature and to use them as reference for the analysis. The occurrence sample of the discourse marker pues was taken from the PRESEEA-Medellín corpus. Seven functions were found for this marker in that speech community, of which one was not registered in the reviewed literature. Thus, the article contributes to the expansion of the description of this marker in Spanish in general and opens up new possibilities for further research on the use of the discourse marker pues.

  16. Virus-Induced Gene Silencing-Based Functional Analyses Revealed the Involvement of Several Putative Trehalose-6-Phosphate Synthase/Phosphatase Genes in Disease Resistance against Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 in Tomato

    Science.gov (United States)

    Zhang, Huijuan; Hong, Yongbo; Huang, Lei; Liu, Shixia; Tian, Limei; Dai, Yi; Cao, Zhongye; Huang, Lihong; Li, Dayong; Song, Fengming

    2016-01-01

    Trehalose and its metabolism have been demonstrated to play important roles in control of plant growth, development, and stress responses. However, direct genetic evidence supporting the functions of trehalose and its metabolism in defense response against pathogens is lacking. In the present study, genome-wide characterization of putative trehalose-related genes identified 11 SlTPSs for trehalose-6-phosphate synthase, 8 SlTPPs for trehalose-6-phosphate phosphatase and one SlTRE1 for trehalase in tomato genome. Nine SlTPSs, 4 SlTPPs, and SlTRE1 were selected for functional analyses to explore their involvement in tomato disease resistance. Some selected SlTPSs, SlTPPs, and SlTRE1 responded with distinct expression induction patterns to Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst) DC3000 as well as to defense signaling hormones (e.g., salicylic acid, jasmonic acid, and a precursor of ethylene). Virus-induced gene silencing-mediated silencing of SlTPS3, SlTPS4, or SlTPS7 led to deregulation of ROS accumulation and attenuated the expression of defense-related genes upon pathogen infection and thus deteriorated the resistance against B. cinerea or Pst DC3000. By contrast, silencing of SlTPS5 or SlTPP2 led to an increased expression of the defense-related genes upon pathogen infection and conferred an increased resistance against Pst DC3000. Silencing of SlTPS3, SlTPS4, SlTPS5, SlTPS7, or SlTPP2 affected trehalose level in tomato plants with or without infection of B. cinerea or Pst DC3000. These results demonstrate that SlTPS3, SlTPS4, SlTPS5, SlTPS7, and SlTPP2 play roles in resistance against B. cinerea and Pst DC3000, implying the importance of trehalose and tis metabolism in regulation of defense response against pathogens in tomato. PMID:27540389

  17. Discovery of Putative Herbicide Resistance Genes and Its Regulatory Network in Chickpea Using Transcriptome Sequencing

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    Mir A. Iquebal

    2017-06-01

    Full Text Available Background: Chickpea (Cicer arietinum L. contributes 75% of total pulse production. Being cheaper than animal protein, makes it important in dietary requirement of developing countries. Weed not only competes with chickpea resulting into drastic yield reduction but also creates problem of harboring fungi, bacterial diseases and insect pests. Chemical approach having new herbicide discovery has constraint of limited lead molecule options, statutory regulations and environmental clearance. Through genetic approach, transgenic herbicide tolerant crop has given successful result but led to serious concern over ecological safety thus non-transgenic approach like marker assisted selection is desirable. Since large variability in tolerance limit of herbicide already exists in chickpea varieties, thus the genes offering herbicide tolerance can be introgressed in variety improvement programme. Transcriptome studies can discover such associated key genes with herbicide tolerance in chickpea.Results: This is first transcriptomic studies of chickpea or even any legume crop using two herbicide susceptible and tolerant genotypes exposed to imidazoline (Imazethapyr. Approximately 90 million paired-end reads generated from four samples were processed and assembled into 30,803 contigs using reference based assembly. We report 6,310 differentially expressed genes (DEGs, of which 3,037 were regulated by 980 miRNAs, 1,528 transcription factors associated with 897 DEGs, 47 Hub proteins, 3,540 putative Simple Sequence Repeat-Functional Domain Marker (SSR-FDM, 13,778 genic Single Nucleotide Polymorphism (SNP putative markers and 1,174 Indels. Randomly selected 20 DEGs were validated using qPCR. Pathway analysis suggested that xenobiotic degradation related gene, glutathione S-transferase (GST were only up-regulated in presence of herbicide. Down-regulation of DNA replication genes and up-regulation of abscisic acid pathway genes were observed. Study further reveals

  18. Assessment of Functional EST-SSR Markers (Sugarcane in Cross-Species Transferability, Genetic Diversity among Poaceae Plants, and Bulk Segregation Analysis

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    Shamshad Ul Haq

    2016-01-01

    Full Text Available Expressed sequence tags (ESTs are important resource for gene discovery, gene expression and its regulation, molecular marker development, and comparative genomics. We procured 10000 ESTs and analyzed 267 EST-SSRs markers through computational approach. The average density was one SSR/10.45 kb or 6.4% frequency, wherein trinucleotide repeats (66.74% were the most abundant followed by di- (26.10%, tetra- (4.67%, penta- (1.5%, and hexanucleotide (1.2% repeats. Functional annotations were done and after-effect newly developed 63 EST-SSRs were used for cross transferability, genetic diversity, and bulk segregation analysis (BSA. Out of 63 EST-SSRs, 42 markers were identified owing to their expansion genetics across 20 different plants which amplified 519 alleles at 180 loci with an average of 2.88 alleles/locus and the polymorphic information content (PIC ranged from 0.51 to 0.93 with an average of 0.83. The cross transferability ranged from 25% for wheat to 97.22% for Schlerostachya, with an average of 55.86%, and genetic relationships were established based on diversification among them. Moreover, 10 EST-SSRs were recognized as important markers between bulks of pooled DNA of sugarcane cultivars through BSA. This study highlights the employability of the markers in transferability, genetic diversity in grass species, and distinguished sugarcane bulks.

  19. Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Montoya, Jessica L; Iudicello, Jennifer; Fazeli, Pariya L; Hong, Suzi; Potter, Michael; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; Moore, David J

    2017-02-01

    HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (β = 0.41, P function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P quadratic association with neurocognitive function (β = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.

  20. The methanol dehydrogenase gene, mxaF, as a functional and phylogenetic marker for proteobacterial methanotrophs in natural environments.

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    Evan Lau

    Full Text Available The mxaF gene, coding for the large (α subunit of methanol dehydrogenase, is highly conserved among distantly related methylotrophic species in the Alpha-, Beta- and Gammaproteobacteria. It is ubiquitous in methanotrophs, in contrast to other methanotroph-specific genes such as the pmoA and mmoX genes, which are absent in some methanotrophic proteobacterial genera. This study examined the potential for using the mxaF gene as a functional and phylogenetic marker for methanotrophs. mxaF and 16S rRNA gene phylogenies were constructed based on over 100 database sequences of known proteobacterial methanotrophs and other methylotrophs to assess their evolutionary histories. Topology tests revealed that mxaF and 16S rDNA genes of methanotrophs do not show congruent evolutionary histories, with incongruencies in methanotrophic taxa in the Methylococcaceae, Methylocystaceae, and Beijerinckiacea. However, known methanotrophs generally formed coherent clades based on mxaF gene sequences, allowing for phylogenetic discrimination of major taxa. This feature highlights the mxaF gene's usefulness as a biomarker in studying the molecular diversity of proteobacterial methanotrophs in nature. To verify this, PCR-directed assays targeting this gene were used to detect novel methanotrophs from diverse environments including soil, peatland, hydrothermal vent mussel tissues, and methanotroph isolates. The placement of the majority of environmental mxaF gene sequences in distinct methanotroph-specific clades (Methylocystaceae and Methylococcaceae detected in this study supports the use of mxaF as a biomarker for methanotrophic proteobacteria.

  1. Molecular cloning, sequence analysis, and function of the intestinal epithelial stem cell marker Bmi1 in pig intestinal epithelial cells.

    Science.gov (United States)

    Li, C-M; Yan, H-C; Fu, H-L; Xu, G-F; Wang, X-Q

    2014-01-01

    In the present work, we cloned the full-length cDNA of the pig Bmi1 gene (BMI1 polycomb ring finger oncogene), which has been indicated as an intestinal epithelial stem cell (IESC) marker in other mammals. This paper provides the first report of the function of Bmi1 in pig intestinal epithelial cells and a brief description of its underlying mechanism. Rapid amplification of cDNA ends technology was used to clone the complete pig Bmi1 sequence, and a Bmi1-pcDNA3.1 vector was constructed for transfection into an intestinal porcine epithelial cell line (IPEC-1). The proliferation ability of the cells was estimated using the MTT assay and the EdU incorporation method at different time points after seeding. Cell cycle information was detected by flow cytometry. The mRNA abundances of cell cycle-related genes were also measured. The results indicated that the pig Bmi1 cDNA is 3,193 bp in length and consists of a 981 bp open reading frame, a 256 bp 5´ untranslated region (UTR), and a 1,956 bp 3' UTR. The transcript contains no signal peptides, and there are no transmembrane regions in the pig Bmi1 coded protein, which has a total of 326 AA. The overexpression of the pig Bmi1 in the IPEC-1 cells led to increased cell proliferation and a lower percentage of cells in the G1 and S phases (P cells in the G2 phase (P 0.05). Our data suggested that pig Bmi1 can increase the proliferation of IPEC-1 cells by promoting the G1/S transition and the overall cell cycle process.

  2. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  3. Relationship between markers of insulin resistance, markers of adiposity, HbA1c, and cognitive functions in a middle-aged population-based sample: the MONA LISA study.

    Science.gov (United States)

    Sanz, Caroline M; Ruidavets, Jean-Bernard; Bongard, Vanina; Marquié, Jean-Claude; Hanaire, Hélène; Ferrières, Jean; Andrieu, Sandrine

    2013-06-01

    To determine the relationship between markers of insulin resistance (fasting insulin and homeostasis model assessment of insulin resistance), markers of adiposity (BMI, waist circumference, and body fat), HbA1c, and cognitive performances in a middle-aged population-based sample free of diabetes. Our study sample consisted of 1,172 people aged 35-64 years (49% women), free of diabetes, and recruited between 2005 and 2007 in the MONA LISA survey. Cognitive functions (memory, attention, and processing speed) were evaluated by neuropsychological tests: word-list learning test, digit symbol substitution test (DSST), word fluency test, and Stroop Test. Multiple logistic regressions were used to estimate the relationship between cognitive performance and metabolic markers. We serially adjusted for age, sex, education, and occupational status (model A), additionally for income, smoking, alcohol consumption, sedentarity, and psychotropic substance use (model B), and finally, included variables linked to the metabolic syndrome (hypertension, dyslipidemia, vascular disease, and C-reactive protein) and depression (model C). Elevated markers of adiposity were associated with poor cognitive performance in tests evaluating processing speed. The probability of being in the lowest quartile of each test was nearly doubled for participants in the upper quartile of BMI, compared with those in the lowest one [BMI, adjusted odds ratio (OR) 2.18, P = 0.003 (DSST), and OR 2.09, P = 0.005 (Stroop Test)]. High HbA1c was associated with poor cognitive performance in DSST (adjusted OR 1.75, P = 0.037). Waist circumference was linked to poor cognitive performance in men but not in women. Poor cognitive performance is associated with adiposity and hyperglycemia in healthy middle-aged people.

  4. Relationship Between Markers of Insulin Resistance, Markers of Adiposity, HbA1c, and Cognitive Functions in a Middle-Aged Population–Based Sample: the MONA LISA Study

    Science.gov (United States)

    Sanz, Caroline M.; Ruidavets, Jean-Bernard; Bongard, Vanina; Marquié, Jean-Claude; Hanaire, Hélène; Ferrières, Jean; Andrieu, Sandrine

    2013-01-01

    OBJECTIVE To determine the relationship between markers of insulin resistance (fasting insulin and homeostasis model assessment of insulin resistance), markers of adiposity (BMI, waist circumference, and body fat), HbA1c, and cognitive performances in a middle-aged population–based sample free of diabetes. RESEARCH DESIGN AND METHODS Our study sample consisted of 1,172 people aged 35–64 years (49% women), free of diabetes, and recruited between 2005 and 2007 in the MONA LISA survey. Cognitive functions (memory, attention, and processing speed) were evaluated by neuropsychological tests: word-list learning test, digit symbol substitution test (DSST), word fluency test, and Stroop Test. Multiple logistic regressions were used to estimate the relationship between cognitive performance and metabolic markers. We serially adjusted for age, sex, education, and occupational status (model A), additionally for income, smoking, alcohol consumption, sedentarity, and psychotropic substance use (model B), and finally, included variables linked to the metabolic syndrome (hypertension, dyslipidemia, vascular disease, and C-reactive protein) and depression (model C). RESULTS Elevated markers of adiposity were associated with poor cognitive performance in tests evaluating processing speed. The probability of being in the lowest quartile of each test was nearly doubled for participants in the upper quartile of BMI, compared with those in the lowest one [BMI, adjusted odds ratio (OR) 2.18, P = 0.003 (DSST), and OR 2.09, P = 0.005 (Stroop Test)]. High HbA1c was associated with poor cognitive performance in DSST (adjusted OR 1.75, P = 0.037). Waist circumference was linked to poor cognitive performance in men but not in women. CONCLUSIONS Poor cognitive performance is associated with adiposity and hyperglycemia in healthy middle-aged people. PMID:23275371

  5. Effects of circulation hyperthermic perfusion chemotherapy on tumor marker content and PI3K/Akt/mTOR pathway function of gastric cancer peritoneal effusion patients

    Institute of Scientific and Technical Information of China (English)

    Li Ding

    2015-01-01

    Objective: To study the effects of circulation hyperthermic perfusion chemotherapy on tumor marker content and PI3K/Akt/mTOR pathway function of gastric cancer peritoneal effusion patients. Methods: 80 cases of gastric cancer peritoneal effusion patients in our hospital from May 2013 to August 2014 were enrolled and randomly divided into two groups. Observation group received circulation hyperthermic perfusion chemotherapy; control group received conventional perfusion chemotherapy. Then blood tumor markers, LAG3 and HSP content, PI3K-AKT-mTOR signal molecules were assayed. Results:(1) tumor markers: DDK1, EXOSC2 contents and PGR ratio of observation group were lower than those of control group; PGI and PGII contents were higher than those of control group; (2) LAG3 and HSP contents: HSP27 and HSP90 contents of observation group were lower than those of control group; sLAG-3 content was higher than that of control group; (3) signal molecules: mRNA contents of PI3K, Akt and mTOR molecules of observation group were lower than those of control group. Conclusion: Circulation hyperthermic perfusion chemotherapy is helpful to kill tumor cells, reduce tumor marker releasing into blood, regulate LAG3 and HSP expression and inhibit PI3K/Akt/mTOR pathway function; it’s an ideal method for treating peritoneal effusion.

  6. Correlations between functional imaging markers derived from PET/CT and diffusion-weighted MRI in diffuse large B-cell lymphoma and follicular lymphoma.

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    Xingchen Wu

    Full Text Available OBJECTIVES: To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT and diffusion-weighted magnetic resonance imaging (DWI in diffuse large B-cell lymphoma (DLBCL and follicular lymphoma (FL. Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkin's lymphoma (NHL. MATERIALS AND METHODS: Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUV(max, metabolic tumor volume (MTV, and metabolic tumor burden (MTB were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm(2. The minimum and mean apparent diffusion coefficient (ADC(min and ADC(mean were measured on the parametric ADC maps. RESULTS: The SUV(max correlated inversely with the ADC(min (r =  -0.35, p<0.05. The ADC(min, ADC(mean, serum thymidine kinase (TK, Beta 2-microglobulin (B2m, lactate dehydrogenase (LD, and C-reactive protein (CRP correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01. The SUV(max, TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL. CONCLUSIONS: The functional imaging markers determined from PET/CT and DWI are associated, and the SUV(max is superior to the ADC(min in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.

  7. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins.

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    Siddarth Soni

    Full Text Available Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID. The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue.General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2, Nexilin (NEXN, Popeye-domain-containg-protein 2 (POPDC2 and thioredoxin-related-transmembrane-protein 2 (TMX2 and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes.The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart.

  8. Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

    Science.gov (United States)

    Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Zwart, Sara R.; Macias, Brandon R.; Hargans, Alan R.; Sharma, Kumar; De Vivo, Immaculata

    2017-01-01

    that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

  9. Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

    Science.gov (United States)

    Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Macias, Brandon R.; Hargens, Alan R.; Sharma, Kumar; De Vivo, Immaculata

    2016-01-01

    atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

  10. NABIC marker database: A molecular markers information network of agricultural crops

    OpenAIRE

    2013-01-01

    In 2013, National Agricultural Biotechnology Information Center (NABIC) reconstructs a molecular marker database for useful genetic resources. The web-based marker database consists of three major functional categories: map viewer, RSN marker and gene annotation. It provides 7250 marker locations, 3301 RSN marker property, 3280 molecular marker annotation information in agricultural plants. The individual molecular marker provides information such as marker name, expressed sequence tag number...

  11. Subclinical Hypothyroidism and the Effect of Autoimmunity on the Echocardiography Indices of Left Ventricular Function, Lipid Profile, and Inflammatory Markers

    Directory of Open Access Journals (Sweden)

    Zohreh Moossavi

    2015-03-01

    Full Text Available Background: Subclinical hypothyroidism (Sch is the most frequent thyroid disease. The relationship between overt hypothyroidism and cardiovascular diseases has been well documented, but conflicting data have remained regarding Sch. Objectives: The present study aimed to assess the effect of Sch on increasing the risk of cardiovascular involvement considering the autoimmune subset. Patients and Methods: This case-control study was conducted on thirty patients with Sch and 30 healthy controls. Serum levels of thyroperoxidase antibody (TPOab, lipids, hsCRP, homocysteine, and ferritin were measured. Besides, conventional echocardiographic study and tissue Doppler imaging (including strain rate indices was done to evaluate Left Ventricular (LV systolic function. Results: The results showed a significant difference between the Sch patients and the controls regarding the serum level of triglyceride (117.43 ± 63.51 mg/dL vs. 86.86 ± 41.57, P = 0.031, echocardiographic parameters (longitudinal systolic strain rate [SRs: -1.006 ± 0.4 vs. -1.26 ± 0.16, P = 0.002; SRl: -1.43 ± 0.27 vs. -1.68 ± 0.29, P = 0.001], and Sm of septal mitral annulus (6.90 ± 0.6 vs. 7.43 ± 0.8, P = 0.006]. However, no significant difference was observed between the two groups regarding the serum levels of the inflammatory markers. Moreover, a significant correlation was found between TSH and Sm (r = -0.36, P = 0.005 and longitudinal systolic strain rate (SRs: r = 0.42, P < 0.001; SRl: r = 0.40, P = 0.001. Systolic strain rate was significantly lower in the TPOab positive patients (-0.99 ± 0.18 vs. -1.15 ± 0.25, P = 0.047. Conclusions: The clear association between Sch and subclinical LV systolic dysfunction which was more evident in the subgroup of patients with circulating anti-thyroid antibodies would remind a greater emphasis for considering the subgroup of TPOab positive patients for directing toward hormone replacement.

  12. A Single-Tube, Functional Marker-Based Multiplex PCR Assay for Simultaneous Detection of Major Bacterial Blight Resistance GenesXa21, xa13 andxa5 in Rice

    Institute of Scientific and Technical Information of China (English)

    S. K. HAJIRA; M. ANILA; S. BHASKAR; V. ABHILASH; H. K. MAHADEVASWAMY; M. KOUSIK; T. DILIPKUMAR; G. HARIKA; G. REKHA; R. M. SUNDARAM; G. S. LAHA; A. YUGANDER; S. M. BALACHANDRAN; B. C. VIRAKTAMATH; K. SUJATHA; C. H. BALACHIRANJEEVI; K. PRANATHI

    2016-01-01

    In marker-assisted breeding for bacterial blight (BB) resistance in rice, three major resistance genes, viz.,Xa21, xa13andxa5,are routinely deployed either singly or in combinations. As efficient and functional markers are yet to be developed forxa13 andxa5,we have developed simple PCR-based functional markers for both the genes.Forxa13,we designed a functional PCR-based marker, xa13-prom targeting the InDel polymorphism in the promoter of candidate geneOs8N3 located on chromosome 8 of rice. With respect toxa5, a multiplex-PCR based functional marker system, named xa5FM, consisting of two sets of primer pairs targeting the 2-bp functional nucleotide polymorphism in the exon II of the geneTFIIAɤ5 (candidate forxa5), has been developed. Both xa13-prom and xa5FM can differentiate the resistant and susceptible alleles forxa13 andxa5, respectively, in a co-dominant fashion. Using these two functional markers along with the already reported functional PCR-based marker forXa21 (pTA248),we designed a single-tube multiplex PCR based assay for simultaneous detection of all the three major resistance genes and demonstrated the utility of the multiplex marker system in a segregating population.

  13. Linkage mapping of putative regulator genes of barley grain development characterized by expression profiling

    Directory of Open Access Journals (Sweden)

    Wobus Ulrich

    2009-01-01

    Full Text Available Abstract Background Barley (Hordeum vulgare L. seed development is a highly regulated process with fine-tuned interaction of various tissues controlling distinct physiological events during prestorage, storage and dessication phase. As potential regulators involved within this process we studied 172 transcription factors and 204 kinases for their expression behaviour and anchored a subset of them to the barley linkage map to promote marker-assisted studies on barley grains. Results By a hierachical clustering of the expression profiles of 376 potential regulatory genes expressed in 37 different tissues, we found 50 regulators preferentially expressed in one of the three grain tissue fractions pericarp, endosperm and embryo during seed development. In addition, 27 regulators found to be expressed during both seed development and germination and 32 additional regulators are characteristically expressed in multiple tissues undergoing cell differentiation events during barley plant ontogeny. Another 96 regulators were, beside in the developing seed, ubiquitously expressed among all tissues of germinating seedlings as well as in reproductive tissues. SNP-marker development for those regulators resulted in anchoring 61 markers on the genetic linkage map of barley and the chromosomal assignment of another 12 loci by using wheat-barley addition lines. The SNP frequency ranged from 0.5 to 1.0 SNP/kb in the parents of the various mapping populations and was 2.3 SNP/kb over all eight lines tested. Exploration of macrosynteny to rice revealed that the chromosomal orders of the mapped putative regulatory factors were predominantly conserved during evolution. Conclusion We identified expression patterns of major transcription factors and signaling related genes expressed during barley ontogeny and further assigned possible functions based on likely orthologs functionally well characterized in model plant species. The combined linkage map and reference

  14. Urinary Metalloproteinases-9 and -2 and Their Inhibitors TIMP-1 and TIMP-2 are Markers of Early and Long-Term Graft Function After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Ewa Kwiatkowska

    2016-05-01

    Full Text Available Background/Aims: Renal ischemia-reperfusion (I-R injury (IRI is an inseparable feature of organ transplantation and may have a negative impact on the graft, its function and survival. Acute tubular necrosis, which is reversible thanks to the regenerative capacity of renal tubular epithelial cells, is the main cause of acute renal failure secondary to IRI. MMP-2 and MMP-9 are proteolytic enzymes involved in digesting proteins that are components of the extracellular matrix (ECM and the basement membrane of the nephrons. This way post-reperfusion MMP activation allows the inflammatory process to spread. Methods: In our studies, we focused on identifying whether the concentrations of MMP-2 and MMP-9 and their natural inhibitors TIMP-1 and TIMP-2 in urine sample at day 1 and day 30 as well as after 12 months following renal transplantation are markers of early and long-term renal function during meanly five-years observation. Moreover, in urine sampled at months 6 and 12 after renal transplantation, we determined the content of TGF-β as a graft fibrosis indicator. Results: MMP-9 concentration in the early post-transplant period is a major marker of early and long-term function of the transplanted kidney. Its increased concentration was correlated with lesions related to tubular atrophy and fibrosis in renal biopsies performed at months 3 and 12 after transplantation. Its concentration is correlated with TGF-β content in a later period. Conclusions: TIMP-1 and-2 are primarily markers of an early function of the transplanted kidney. Early post-transplant concentration of MMP-2 is a marker of proteinuria in early and long-term post-transplant periods.

  15. A functional MRI marker may predict the outcome of electroconvulsive therapy in severe and treatment-resistant depression

    NARCIS (Netherlands)

    van Waarde, J.A.; Scholte, H.S.; van Oudheusden, L.J.B.; Verwey, B.; Denys, D.; van Wingen, G.A.

    2015-01-01

    Electroconvulsive therapy (ECT) is effective even in treatment-resistant patients with major depression. Currently, there are no markers available that can assist in identifying those patients most likely to benefit from ECT. In the present study, we investigated whether resting-state network connec

  16. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay;

    2015-01-01

    Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chro...

  17. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay

    2015-01-01

    Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chro...

  18. Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver function test markers in type 2 diabetes mellitus subjects - pilot study.

    Science.gov (United States)

    Ghadge, A; Harke, S; Khadke, S; Diwan, A; Pankaj, M; Kulkarni, O; Ranjekar, P; Harsulkar, A; Kuvalekar, A A

    2015-09-01

    The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. Superoxide dismutase activity was higher (plevels were higher in diabetic male subjects while urea (plevels were lower and SGPT (plevels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (pantioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments. © Georg Thieme Verlag KG Stuttgart · New York.

  19. [The relationship between nutritional status and oxidative stress markers, pulmonary function in patients with stable chronic obstructive pulmonary disease].

    Science.gov (United States)

    Jiang, X L; Zhong, P; Huang, C L; He, F; Fan, X M; Chen, X R

    2017-01-12

    Objective: To investigate the association between the nutritional status of patients with chronic obstructive pulmonary disease (COPD) and the levels of serum oxidative stress markers protein carbonyls (PC), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (TAC) and pulmonary function. Methods: 200 patients with stable COPD (the COPD group) and 100 healthy individuals (the control group) who visited during June 2014 and August 2014 were enrolled in our study. The levels of PC, MDA, 8-OHdG and TAC in serum were detected. Pulmonary function was tested. Nutritional status was assessed by mini nutritional assessment (MNA) that classified the nutrition class. Results: The levels of PC, MDA, and 8-OHdG in serum increased significantly in the COPD group [3.82 (1.79, 6.83) μg/L, 3.89(2.77, 5.40) μmol/L and 359.18(259.25, 587.85) ng/L, respectively], and the levels of TAC in serum decreased significantly in COPD group [11.35(4.81, 20.20)U/ml], as compared with the control group [2.29(1.08, 3.26) μg/L, 3.08(2.32, 4.03) μmol/L, 311.37(265.47, 374.08) ng/L and 18.81(15.21, 23.19) U/ml, respectively, all Pnutrition assessment parameters were gradually decreased as nutritional status worsen (all P<0.05). In malnourished (risk) COPD subgroup, the levels of PC and TAC in serum increased significantly [6.10(3.02, 8.18) μg/L and 13.33(6.07, 23.96) U/ml, respectively] and the FEV(1)% and FEV(1)/FVC index decreased significantly [42.90(34.68, 71.23) and 46.96(38.96, 60.63), respectively] as compared the well-nourished COPD subgroup [3.25(1.61, 5.37) μg/L, 9.99(4.41, 16.77) U/ml, 69.10(45.95, 89.23) and 53.32(42.13, 63.15), all P<0.05]. Furthermore, we had found that the upper arm muscle circumference, calf circumference and BMI were positively correlated with MNA (r=0.498, 0.587, 0.781, P<0.001), negatively correlated with PC (r=-0.209, -0.195, -0.231, P<0.05) and positively correlated with FEV(1)% (r=0.223, 0.274, 0.350, P<0.05). The upper

  20. Accumulation of MRI markers of cerebral small vessel disease is associated with decreased cognitive function. A study in first-ever lacunar stroke and hypertensive patients.

    Directory of Open Access Journals (Sweden)

    Marjolein eHuijts

    2013-11-01

    Full Text Available Background – White matter lesions (WMLs, asymptomatic lacunar infarcts, brain microbleeds (BMBs and enlarged perivascular spaces (EPVS have been identified as silent lesions due to cerebral small vessel disease (cSVD. All these markers have been individually linked to cognitive functioning, but are also strongly correlated with each other. The combined effect of these markers on cognitive function has never been studied and would possibly provide more useful information on the effect on cognitive function. Methods – Brain MRI and extensive neuropsychological assessment were performed in 189 patients at risk for cSVD (112 hypertensive patients and 77 first-ever lacunar stroke patients. We rated the presence of any asymptomatic lacunar infarct, extensive WMLs, any deep BMB, and moderate to extensive EPVS in the basal ganglia. The presence of each marker was summed to an ordinal score between 0 and 4. Associations with domains of cognitive function (memory, executive function, information processing speed and overall cognition were analyzed with correlation analyses. Results – Correlation analyses revealed significant associations between accumulating cSVD burden and decreased performance on all cognitive domains (all p≤.001. Results remained significant for information processing speed (r=-.181, p=.013 and overall cognition (r=-.178, p=.017, after correction for age and sex. Testing of trend using linear regression analyses revealed the same results. Discussion – We tested a new approach to capture total brain damage resulting from cSVD and found that accumulation of MRI burden of cSVD is associated with decreased performance on tests of information processing speed and overall cognition, implying that accumulating brain damage is accompanied by worse cognitive functioning.

  1. Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites

    DEFF Research Database (Denmark)

    Silveira, Cássia G T; Abrão, Mauricio S; Dias, João A

    2012-01-01

    BACKGROUND: Endometriosis is a multifactorial gynecological disease characterized by the presence of functional endometrium-like tissue in ectopic sites. Several studies have focused on elucidating the immunological, endocrine, environmental and genetic factors involved in endometriosis. However...... genomic alterations in stromal and epithelial cells from different anatomical sites of the same patient and the expression of stemness-related markers suggested that endometriosis arises as a clonal proliferation with the putative involvement of stem cells....

  2. (SSR) markers

    African Journals Online (AJOL)

    SAM

    2014-07-30

    Jul 30, 2014 ... Simple sequence repeats (SSRs) are the most widely used marker system for plant variety characterization and ... gene tagging in marker assisted breeding and gene cloning in .... PLS-2 and PAU Selection Long) to 1.00 (between PC. 2062 and .... Comparative analyses of genetic diversities within tomato.

  3. (SSR) markers

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... seeded and black-seeded cultivars and breeding lines. The group B included 70 ... maize, rice and tomatoes (Reif et al., 2006; Vigouroux et al., 2005; Warburton et ..... development of molecular markers for marker-assisted breeding. .... Selection under domestication: evidence for a sweep in the rice Waxy ...

  4. Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke

    Science.gov (United States)

    2013-01-01

    Introduction Stem cell therapy can promote good recovery from stroke. Several studies have demonstrated that mesenchymal stem cells (MSC) are safe and effective. However, more information regarding appropriate cell type is needed from animal model. This study was targeted at analyzing the effects in ischemic stroke of acute intravenous (i.v.) administration of allogenic bone marrow- (BM-MSC) and adipose-derived-stem cells (AD-MSC) on functional evaluation results and brain repair markers. Methods Allogenic MSC (2 × 106 cells) were administered intravenously 30 minutes after permanent middle cerebral artery occlusion (pMCAO) to rats. Infarct volume and cell migration and implantation were analyzed by magnetic resonance imaging (MRI) and immunohistochemistry. Function was evaluated by the Rogers and rotarod tests, and cell proliferation and cell-death were also determined. Brain repair markers were analyzed by confocal microscopy and confirmed by western blot. Results Compared to infarct group, function had significantly improved at 24 h and continued at 14 d after i.v. administration of either BM-MSC or AD-MSC. No reduction in infarct volume or any migration/implantation of cells into the damaged brain were observed. Nevertheless, cell death was reduced and cellular proliferation significantly increased in both treatment groups with respect to the infarct group. At 14 d after MSC administration vascular endothelial growth factor (VEGF), synaptophysin (SYP), oligodendrocyte (Olig-2) and neurofilament (NF) levels were significantly increased while those of glial fiibrillary acid protein (GFAP) were decreased. Conclusions i.v. administration of allogenic MSC - whether BM-MSC or AD-MSC, in pMCAO infarct was associated with good functional recovery, and reductions in cell death as well as increases in cellular proliferation, neurogenesis, oligodendrogenesis, synaptogenesis and angiogenesis markers at 14 days post-infarct. PMID:23356495

  5. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Ryuta Shigefuku

    2016-09-01

    Full Text Available The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC and nonalcoholic fatty liver disease (NAFLD by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF. Xenon computed tomography (Xe-CT was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC. The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC was significantly lower than that in hepatitis C virus (C-LC (p = 0.014. Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05. It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  6. Construction of a restriction-less, marker-less mutant useful for functional genomic and metabolic engineering of the biofuel producer Clostridium acetobutylicum.

    Science.gov (United States)

    Croux, Christian; Nguyen, Ngoc-Phuong-Thao; Lee, Jieun; Raynaud, Céline; Saint-Prix, Florence; Gonzalez-Pajuelo, Maria; Meynial-Salles, Isabelle; Soucaille, Philippe

    2016-01-01

    Clostridium acetobutylicum is a gram-positive, spore-forming, anaerobic bacterium capable of converting various sugars and polysaccharides into solvents (acetone, butanol, and ethanol). The sequencing of its genome has prompted new approaches to genetic analysis, functional genomics, and metabolic engineering to develop industrial strains for the production of biofuels and bulk chemicals. The method used in this paper to knock-out or knock-in genes in C. acetobutylicum combines the use of an antibiotic-resistance gene for the deletion or replacement of the target gene, the subsequent elimination of the antibiotic-resistance gene with the flippase recombinase system from Saccharomyces cerevisiae, and a C. acetobutylicum strain that lacks upp, which encodes uracil phosphoribosyl-transferase, for subsequent use as a counter-selectable marker. A replicative vector containing (1) a pIMP13 origin of replication from Bacillus subtilis that is functional in Clostridia, (2) a replacement cassette consisting of an antibiotic resistance gene (MLS (R) ) flanked by two FRT sequences, and (3) two sequences homologous to selected regions around target DNA sequence was first constructed. This vector was successfully used to consecutively delete the Cac824I restriction endonuclease encoding gene (CA_C1502) and the upp gene (CA_C2879) in the C. acetobutylicum ATCC824 chromosome. The resulting C. acetobutylicum Δcac1502Δupp strain is marker-less, readily transformable without any previous plasmid methylation and can serve as the host for the "marker-less" genetic exchange system. The third gene, CA_C3535, shown in this study to encode for a type II restriction enzyme (Cac824II) that recognizes the CTGAAG sequence, was deleted using an upp/5-FU counter-selection strategy to improve the efficiency of the method. The restriction-less marker-less strain and the method was successfully used to delete two genes (ctfAB) on the pSOL1 megaplasmid and one gene (ldhA) on the chromosome to get

  7. Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems.

    Science.gov (United States)

    Narazaki, Kenji; Matsuo, Eri; Honda, Takanori; Nofuji, Yu; Yonemoto, Koji; Kumagai, Shuzo

    2014-09-01

    Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24) were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%). Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community-based preventive care of dementia. Key pointsThere is a great need for identifying lifestyle-related markers which help detect subtle cognitive impairment in the preclinical or earlier phase of dementia.In the present study, each of the five physical fitness measures

  8. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  9. The effect of resistance training on markers of immune function and inflammation in previously sedentary women recovering from breast cancer: a randomized controlled trial.

    Science.gov (United States)

    Hagstrom, Amanda D; Marshall, Paul W M; Lonsdale, Chris; Papalia, Shona; Cheema, Birinder S; Toben, Catherine; Baune, Bernhard T; Fiatarone Singh, Maria A; Green, Simon

    2016-02-01

    The purpose of this randomized controlled trial was to determine the effects of resistance training (RT) on markers of inflammation and immune function in breast cancer survivors. Thirty-nine breast cancer survivors were randomly assigned to a RT (n = 20) or control (n = 19) group. RT performed supervized exercise three times per week. Natural killer cell (NK) and natural killer T-cell (NKT) function, and markers of inflammation (serum TNF-α, IL-6, IL-10, and CRP) were measured before and after training. Changes in NK and NKT cell function were analyzed using ANCOVA, with the change score the dependent variable, and the baseline value of the same variable the covariate. Effect sizes (ES) were calculated via partial eta-squared. We found a significant reduction, and large associated ESs, in the RT group compared to the control group for change in NK cell expression of TNF-α (p = 0.005, ES = 0.21) and NKT cell expression of TNF-α (p = 0.04, ES = 0.12). No differences were observed in any serum marker. Significant improvements in all measurements of strength were found in RT compared to control (p < 0.001; large ESs ranging from 0.32 to 0.51). These data demonstrate that RT has a beneficial effect on the NK and NKT cell expression of TNF-α indicating that RT may be beneficial in improving the inflammatory profile in breast cancer survivors.

  10. The Biogeography of Putative Microbial Antibiotic Production.

    Directory of Open Access Journals (Sweden)

    Hélène Morlon

    Full Text Available Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics.

  11. Mechanosensory neurons, cutaneous mechanoreceptors, and putative mechanoproteins.

    Science.gov (United States)

    Del Valle, M E; Cobo, T; Cobo, J L; Vega, J A

    2012-08-01

    The mammalian skin has developed sensory structures (mechanoreceptors) that are responsible for different modalities of mechanosensitivity like touch, vibration, and pressure sensation. These specialized sensory organs are anatomically and functionally connected to a special subset of sensory neurons called mechanosensory neurons, which electrophysiologically correspond with Aβ fibers. Although mechanosensory neurons and cutaneous mechanoreceptors are rather well known, the biology of the sense of touch still remains poorly understood. Basically, the process of mechanosensitivity requires the conversion of a mechanical stimulus into an electrical signal through the activation of ion channels that gate in response to mechanical stimuli. These ion channels belong primarily to the family of the degenerin/epithelium sodium channels, especially the subfamily acid-sensing ion channels, and to the family of transient receptor potential channels. This review compiles the current knowledge on the occurrence of putative mechanoproteins in mechanosensory neurons and mechanoreceptors, as well as the involvement of these proteins on the biology of touch. Furthermore, we include a section about what the knock-out mice for mechanoproteins are teaching us. Finally, the possibilities for mechanotransduction in mechanoreceptors, and the common involvement of the ion channels, extracellular membrane, and cytoskeleton, are revisited.

  12. Evaluation of the prognosis as well as tumor marker levels and immune function of Fuzheng Xiaoliu decoction combined with paclitaxel treatment of advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Ping Huang; Jin-Ru Zhang; Xiao-Fang Li; Jian-Guo Wang

    2016-01-01

    Objective:To analyze the effect of Fuzheng Xiaoliu decoction combined with paclitaxel treatment of advanced breast cancer on the prognosis as well as tumor marker levels, immune function and so on.Methods:A total of 40 patients with advanced breast cancer were randomly divided into observation group and control group (n=20), control group received conventional chemotherapy + paclitaxel treatment and observation group received conventional chemotherapy + paclitaxel + Fuzheng Xiaoliu decoction treatment. The survival of two groups of patients was followed up, and serum levels of tumor markers and sex hormones as well as immune function indexes were determined.Results:Progression-free survival and overall survival of observation group were longer than those of control group; after one course of treatment, serum VEGF-A, TK1, IGF-1, CerbB-2, CEA, CA15-3, CA125, E1 and E2 levels of observation group were significantly lower than those of control group while LH and FSH levels were significantly higher than those of control group; CD3+CD4+, CD8+CD28+, CD19+ and CD16+CD56+ expression levels in peripheral blood of observation group were significantly higher than those of control group while CD4+CD25+ and CD8+CD28- expression levels were significantly lower than those of control group.Conclusion:Fuzheng Xiaoliu decoction combined paclitaxel treatment of advanced breast cancer can reduce tumor malignancy and improve the body's immune function, and is of positive significance in optimizing treatment prognosis.

  13. Comparison of Changes in Biochemical Markers for Skeletal Muscles, Hepatic Metabolism, and Renal Function after Three Types of Long-distance Running: Observational Study.

    Science.gov (United States)

    Shin, Kyung-A; Park, Ki Deok; Ahn, Jaeki; Park, Yongbum; Kim, Young-Joo

    2016-05-01

    The purpose of this study is to compare changes in biochemical markers for the skeletal muscles, hepatic metabolism, and renal function based on extreme long-distance running.Among healthy amateur endurance athletes who participated in a marathon, 100 km-, or 308 km ultramarathon, 15 athletes with similar physical and demographic characteristics were chosen to be the subjects in this study, upon completion of each course. The subjects' blood was collected before and after the course to identify biochemical markers for the skeletal muscles, hepatic metabolism, and renal function.After all of the courses, creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatinine were found to be significantly increased compared with values obtained before the race (P running a 308 km race, which is low-intensity running compared with a marathon, and a temporary decline in renal function was higher after completing a 100 km race, which is medium-to-high intensity.

  14. First trimester serum markers to predict preeclampsia.

    Science.gov (United States)

    Huppertz, Berthold; Kawaguchi, Rie

    2012-05-01

    A variety of different biomarkers to predict preeclampsia have been identified in the last ten years. Most of these markers have been detected and quantified in maternal blood, and their potency to predict preeclampsia prior to the onset of clinical symptoms has been evaluated. The amount of such markers depends on various conditions, including the source of the marker (fetal/placental and/or maternal), the interaction of this marker with other proteins in maternal blood as well as the stability of the markers during freezing and thawing. Here we describe two of the putative early, first trimester biomarkers, placental protein 13 and placental growth factor. There is still the hope that - even in the absence of any treatment regimen today - such predictive markers will help to speed the development of a cure for preeclampsia.

  15. Embryonic Stem Cell Markers

    Directory of Open Access Journals (Sweden)

    Lan Ma

    2012-05-01

    Full Text Available Embryonic stem cell (ESC markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other types of cells, especially tumor cells. Currently, the marker-based flow cytometry (FCM technique and magnetic cell sorting (MACS are the most effective cell isolating methods, and a detailed maker list will help to initially identify, as well as isolate ESCs using these methods. In the current review, we discuss a wide range of cell surface and generic molecular markers that are indicative of the undifferentiated ESCs. Other types of molecules, such as lectins and peptides, which bind to ESC via affinity and specificity, are also summarized. In addition, we review several markers that overlap with tumor stem cells (TSCs, which suggest that uncertainty still exists regarding the benefits of using these markers alone or in various combinations when identifying and isolating cells.

  16. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

    Institute of Scientific and Technical Information of China (English)

    GAO Nan; CUI GuangHui; WANG ZhiChong; HUANG Bing; GE Jian; LU Rong; ZHANG KeFei; FAN ZhiGang; LU Li; PENG Zhan

    2007-01-01

    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epidermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immunohistology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epidermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being cocultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  17. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epi-dermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immuno-histology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epi-dermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being co-cultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  18. Effects of DHA-rich fish oil supplementation on the lipid profile, markers of muscle damage, and neutrophil function in wheelchair basketball athletes before and after acute exercise.

    Science.gov (United States)

    Marques, Camila Garcia; Santos, Vinicius Coneglian; Levada-Pires, Adriana Cristina; Jacintho, Thiago Manzoni; Gorjão, Renata; Pithon-Curi, Tânia Cristina; Cury-Boaventura, Maria Fernanda

    2015-06-01

    We investigated the effects of docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on the lipid profile, levels of plasma inflammatory mediators, markers of muscle damage, and neutrophil function in wheelchair basketball players before and after acute exercise. We evaluated 8 male basketball wheelchair athletes before and after acute exercise both prior to (S0) and following (S1) FO supplementation. The subjects were supplemented with 3 g of FO daily for 30 days. The following components were measured: the plasma lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), plasma inflammatory mediators (C-reactive protein, interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, and tumor necrosis factor-α), markers of muscle damage (creatine kinase and lactate dehydrogenase (LDH)), and neutrophil function (cytokine production, phagocytic capacity, loss of membrane integrity, mitochondrial membrane potential, neutral lipid accumulation, phosphatidylserine externalization, DNA fragmentation, and production of reactive oxygen species (ROS)). Acute exercise increased the plasma levels of total cholesterol, LDH, IL1ra, and IL-6, led to the loss of membrane integrity, ROS production, and a high mitochondrial membrane potential in neutrophils, and reduced the phagocytic capacity and IL-6 production by the neutrophils (S0). However, supplementation prevented the increases in the plasma levels of LDH and IL-6, the loss of membrane integrity, and the alterations in ROS production and mitochondrial membrane potential in the neutrophils that were induced by exercise (S1). In conclusion, DHA-rich FO supplementation reduces the markers of muscle damage, inflammatory disturbances, and neutrophil death induced by acute exercise in wheelchair athletes.

  19. High Transferability of Homoeolog-Specific Markers between Bread Wheat and Newly Synthesized Hexaploid Wheat Lines

    Science.gov (United States)

    Zeng, Deying; Luo, Jiangtao; Li, Zenglin; Chen, Gang; Zhang, Lianquan; Ning, Shunzong; Yuan, Zhongwei; Zheng, Youliang; Hao, Ming; Liu, Dengcai

    2016-01-01

    Bread wheat (Triticum aestivum, 2n = 6x = 42, AABBDD) has a complex allohexaploid genome, which makes it difficult to differentiate between the homoeologous sequences and assign them to the chromosome A, B, or D subgenomes. The chromosome-based draft genome sequence of the ‘Chinese Spring’ common wheat cultivar enables the large-scale development of polymerase chain reaction (PCR)-based markers specific for homoeologs. Based on high-confidence ‘Chinese Spring’ genes with known functions, we developed 183 putative homoeolog-specific markers for chromosomes 4B and 7B. These markers were used in PCR assays for the 4B and 7B nullisomes and their euploid synthetic hexaploid wheat (SHW) line that was newly generated from a hybridization between Triticum turgidum (AABB) and the wild diploid species Aegilops tauschii (DD). Up to 64% of the markers for chromosomes 4B or 7B in the SHW background were confirmed to be homoeolog-specific. Thus, these markers were highly transferable between the ‘Chinese Spring’ bread wheat and SHW lines. Homoeolog-specific markers designed using genes with known functions may be useful for genetic investigations involving homoeologous chromosome tracking and homoeolog expression and interaction analyses. PMID:27611704

  20. Physical functions, health-related outcomes, nutritional status, and blood markers in community-dwelling cancer survivors aged 75 years and older.

    Science.gov (United States)

    Ihira, Hikaru; Mizumoto, Atsushi; Makino, Keitarou; Yasuda, Keisuke; Yoko, Yoko; Saitoh, Shigeyuki; Ohnishi, Hirofumi; Furuna, Taketo

    2014-01-01

    A cancer survivor is defined as anyone who has been diagnosed with cancer, from the time of diagnosis through the rest of their life. The purpose of this study was to examine whether physical functions, health-related outcomes, nutritional status and blood markers in community-dwelling cancer survivors aged 75 years and older are different from those who do not have cancer Two hundred seventy-five participants were asked by physicians, nurses, and physical therapists, questions regarding cancer history in a face-to-face interview. Data were collected for demographic information, physical functions, such as handgrip strength, knee extension power, abdominal muscle strength, static standing balance, walking speed and the timed-up-and-go test, health-related outcomes, nutritional status, and blood markers. The measured parameters of survivor diagnosed with cancer were compared with those without a history of cancer. Thirty-seven older adults were previously diagnosed with cancer. Female cancer survivors had lower knee extension power (paged 75 years and older differs from that in women with no history of cancer.

  1. Effects of oily fish intake on cardiovascular risk markers, cognitive function, and behavior in school-aged children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Lauritzen, Lotte; Hauger, Hanne;

    2016-01-01

    and sleep. We will also examine effects on cognitive function (attention, memory, and executive functions) by using standardized tests, behavior and emotions by administering parent-rated questionnaires and child interviews, and we will measure physiological stress response and cortisol levels. We need 150...

  2. Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems

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    Kenji Narazaki, Eri Matsuo, Takanori Honda, Yu Nofuji, Koji Yonemoto, Shuzo Kumagai

    2014-09-01

    Full Text Available Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24 were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%. Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001. These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001. The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community

  3. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  4. Increase in markers of airway inflammation after ozone exposure can be observed also in stable treated asthmatics with minimal functional response to ozone

    Directory of Open Access Journals (Sweden)

    Dente Federico L

    2010-01-01

    Full Text Available Abstract Background The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. Methods Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to either filtered air or ozone (0.3 ppm for 2 hours in a challenge chamber. Pulmonary function (PF was monitored, and patients with FEV1 decrease greater than 10% from pre-challenge value were considered as responders. Immediately after each exposure, exhaled breath condensate (EBC was collected to measure malondialdehyde (MDA. Six hours after each exposure, PF and EBC collection were repeated, and sputum was induced to measure inflammatory cell counts and soluble mediators (IL-8 and neutrophil elastase. The response to ozone was also evaluated according to the presence of polymorphism in oxidative stress related NQO1 and GSTM1 genes. Results After ozone exposure, sputum neutrophils significantly increased in responders (n = 8, but not in nonresponders (n = 15. Other markers of neutrophil activation in sputum supernatant and MDA in EBC significantly increased in all patients, but only in nonresponders the increase was significant. In nonresponders, sputum eosinophils also significantly increased after ozone. There was a positive correlation between ozone-induced FEV1 fall and increase in sputum neutrophils. No difference in functional or inflammatory response to ozone was observed between subjects with or without the combination of NQO1wt- GSTM1null genotypes. Conclusions Markers of neutrophilic inflammation and oxidative stress increase also in asthmatic subjects not responding to ozone. A greater functional response to ozone is associated with greater neutrophil airway recruitment in asthmatic subjects.

  5. Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study

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    Szűcs Dénes

    2012-03-01

    Full Text Available Abstract Background Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG with event-related brain potentials (ERPs in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC, is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. Results EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. Conclusions We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects.

  6. Questionnaire, walking time and button test measures of functional capacity as predictive markers for mortality in rheumatoid arthritis.

    Science.gov (United States)

    Pincus, T; Callahan, L F; Vaughn, W K

    1987-04-01

    Mortality over 9 years in rheumatoid arthritis was studied according to baseline demographic, disease, therapy and comorbidity variables, and measures of functional capacity variables. Significant differences between patients who survived and died over the next 9 years were seen for 8 variables: age, joint count, oral corticosteroid use, presence of concurrent heart disease, formal educational level, and 3 quantitative measures of functional capacity, questionnaire responses regarding activities of daily living, modified walking time and the button test. Five-year survivals of 50% or less were seen in patients with severely dysfunctional values for the 3 quantitative measures of functional capacity. Increased relative risk of mortality according to functional capacity measures was not explained by age, sex, duration of disease, smoking history, joint count, hand radiograph score, grip strength, morning stiffness, formal educational level, oral corticosteroid or parenteral gold use, or various comorbidities, and was not expected by a majority of physicians.

  7. Trypanosoma brucei: a putative RNA polymerase II promoter.

    Science.gov (United States)

    Bayele, Henry K

    2009-12-01

    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  8. A putative plant organelle RNA recognition protein gene is essential for maize kernel development

    Institute of Scientific and Technical Information of China (English)

    Antony M Chettoor; Gibum Yi; Elisa Gomez; Gregorio Hueros; Robert B Meeley; Philip W Becraft

    2015-01-01

    Basal endosperm transfer layer (BETL) cel s are responsible for transferring apoplastic solutes from the maternal pedicel into the endosperm, supplying the grain with compounds required for embryo development and storage reserve accumulation. Here, we analyze the maize (Zea mays L.) empty pericarp6 (emp6) mutant, which causes early arrest in grain development. The Emp6þgene function is required independently in both the embryo and endo-sperm. The emp6 mutant causes a notable effect on the differentiation of BETL cel s; the extensive cel wal ingrowths that distinguish BETL cel s are diminished and BETL marker gene expression is compromised in mutant kernels. Transposon tagging identified the emp6 locus as encoding a putative plant organel e RNA recognition (PORR) protein, 1 of 15 PORR family members in maize. The emp6 transcript is widely detected in plant tissues with highest levels in embryos and developing kernels. EMP6‐green fluorescent protein (GFP) fusion proteins transiently expressed in Nicotiana benthamiana leaves were targeted specifical y to mitochondria. These results suggest that BETL cel differentia-tion might be particularly energy intensive, or alternatively, that mitochondria might confer a developmental function.

  9. Large scale fusion of gray matter and resting-state functional MRI reveals common and shared biological markers across the psychosis spectrum in the B-SNIP cohort

    Directory of Open Access Journals (Sweden)

    Zheng eWang

    2015-12-01

    Full Text Available To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses (schizophrenia (SZ, schizoaffective disorder (SAD, and bipolar I disorder with psychosis (BP and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives and 242 healthy controls. All subjects underwent structural MRI (sMRI and resting-state functional MRI (rs-fMRI scanning. Joint independent analysis (jICA was used to fuse sMRI gray matter (GM and rs-fMRI amplitude of low frequency fluctuations (ALFF data to identify the relationship between the two modalities. Joint ICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal-striatal-thalamic-cerebellar network and structural abnormalities in the default mode network (DMN was found to be common across psychotic diagnoses and correlated with cognitive function, social function and Schizo-Bipolar Scale (SBS scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality. Using a multivariate fused approach involving two widely used imaging markers we demonstrate both shared and distinct biological traits across the psychosis spectrum. Further, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes.

  10. Cartilage Turnover Reflected by Metabolic Processing of Type II Collagen: A Novel Marker of Anabolic Function in Chondrocytes

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    Natasja Stæhr Gudmann

    2014-10-01

    Full Text Available The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP. This is expected to originate primarily from remodeling of hyaline cartilage. A mouse monoclonal antibody (Mab was raised in mouse, targeting specifically PIIBNP (QDVRQPG and used in development of the assay. The specificity, sensitivity, 4-parameter fit and stability of the assay were tested. Levels of PIIBNP were quantified in human serum (0.6–2.2 nM, human amniotic fluid (163–188 nM and sera from different animal species, e.g., fetal bovine serum (851–901 nM with general good linearity (100% (SD 7.6 recovery and good intra- and inter-assay variation (CV% < 10. Dose (0.1 to 100 ng/mL and time (7, 14 and 21 days dependent release of PIIBNP were evaluated in the conditioned medium from bovine cartilage explants (BEX and human cartilage explants (HEX upon stimulation with insulin-like growth factor (IGF-1, transforming growth factor (TGF-β1 and fibroblastic growth factor-2 (FGF-2. TGF-β1 and IGF-1 in concentrations of 10–100 ng/mL significantly (p < 0.05 induced release of PIIBNP in BEX compared to conditions without treatment (WO. In HEX, IGF-1 100 ng/mL was able to induce a significant increase of PIIBNP after one week compared to WO. FGF-2 did not induce a PIIBNP release in our models. To our knowledge this is the first assay, which is able to specifically evaluate PIIBNP excretion. The Pro-C2 assay seems to provide a promising and novel marker of type II collagen formation.

  11. The hippocampus of the eastern rock sengi: cytoarchitecture, markers of neuronal function, principal cell numbers and adult neurogenesis

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    Lutz eSlomianka

    2013-10-01

    Full Text Available The brains of sengis (elephant shrews, order Macroscelidae have long been known to contain a hippocampus that in terms of allometric progression indices is larger than that of most primates and equal in size to that of humans. In this report, we provide descriptions of hippocampal cytoarchitecture in the eastern rock sengi (Elephantulus myurus, of the distributions of hippocampal calretinin, calbindin, parvalbumin and somatostatin, of principal neuron numbers and of cell numbers related to proliferation and neuronal differentiation in adult hippocampal neurogenesis. Sengi hippocampal cytoarchitecture is an amalgamation of characters that are found in CA1 of, e.g., guinea pig and rabbits and in CA3 and dentate gyrus of primates. Correspondence analysis of total cell numbers and quantitative relations between principal cell populations relate this sengi to macaque monkeys and domestic pigs, and distinguish the sengi from distinct patterns of relations found in humans, dogs and murine rodents. Calretinin and calbindin are present in some cell populations that also express these proteins in other species, e.g., interneurons at the stratum oriens/alveus border or temporal hilar mossy cells, but neurons expressing these markers are often scarce or absent in other layers. The distributions of parvalbumin and somatostatin resemble those in other species. Normalized numbers of PCNA+ proliferating cells and doublecortin+ differentiating cells of neuronal lineage fall within the overall ranges of murid rodents, but differed from three murid species captured in the same habitat in that fewer doublecortin+ cells relative to PCNA+ were observed . The large and well-differentiated sengi hippocampus is not accompanied by correspondingly sized cortical and subcortical limbic areas that are the main hippocampal sources of afferents and targets of efferents. This points to intrinsic hippocampal information processing as the selective advantage of the large sengi

  12. Evaluation of oxidative stress markers for the early diagnosis of allograft rejection in feline renal allotransplant recipients with normal renal function.

    Science.gov (United States)

    Halling, Krista B; Ellison, Gary W; Armstrong, Don; Aoyagi, Kasumi; Detrisac, Carol J; Graham, John P; Newell, Susan P; Martin, Frank G; Van Gilder, James M

    2004-10-01

    The purpose of this study was to identify oxidative damage to renal allografts during graft rejection by evaluating changes in oxidative markers and plasma lactate levels in feline renal allotransplant recipients. Heterotopic renal allotransplantations were performed between 8 adult feline cross-matched donors. Following 14 d of immunosuppression, the drugs were discontinued to allow allograft rejection. Baseline and serial postoperative evaluations of serum creatinine, plasma lactate, plasma thiobarbituate reactive substances (TBARS), plasma creatol, urine creatol, and renal sonographic cross-sectional area were performed. When sonographic evaluation revealed the absence of blood flow to the allograft, the rejected kidney was nephrectomized and evaluated histopathologically. Allograft rejection occurred in all cats by day 26. A significant elevation in body temperature occurred during the rejection period. No significant change was observed between any of the time periods for plasma TBARS, creatol, or urine creatol. There was a significant decrease in plasma lactate levels throughout the study. Markers of oxidative stress from venous blood did not reflect renal allograft rejection in cats with a normally functioning native kidney. Renal allograft rejection may be associated with significant increases in body temperature and warrants further investigation.

  13. The Resistive Index Is a Marker of Renal Function, Pathology, Prognosis, and Responsiveness to Steroid Therapy in Chronic Kidney Disease Patients

    Directory of Open Access Journals (Sweden)

    Kikuno Hanamura

    2012-01-01

    Full Text Available To evaluate the significance of the renal resistive index (RI as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR, and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.5 months revealed that patients with RI≥0.7 (high RI group, n=39 had significantly poorer renal survival than those with RI<0.65 (normal RI group, n=120 and 0.65≤RI<0.7 (high-normal RI group, n=43. The patients in the high-normal RI group showed good response to steroids. However, in the high RI group, steroid therapy did not significantly improve renal survival. Of the clinical indices studied, RI≥0.7, hypertension, proteinuria, and low eGFR at diagnosis were independent risk factors for worsening renal dysfunction. In conclusion, RI in CKD patients was considered as a marker of renal function, histological damage, and renal prognosis, and a possible determinant of indication for steroids.

  14. Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Brain Functional Marker of Auditory Hallucinations in Schizophrenia Patients

    Science.gov (United States)

    Maïza, Olivier; Hervé, Pierre-Yve; Etard, Olivier; Razafimandimby, Annick; Montagne-Larmurier, Aurélie; Dollfus, Sonia

    2013-01-01

    Several cross-sectional functional Magnetic Resonance Imaging (fMRI) studies reported a negative correlation between auditory verbal hallucination (AVH) severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS). Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS) and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz) rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS) cluster, considered henceforward as a functional region of interest (fROI). After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities. PMID:24961421

  15. Impact of Repetitive Transcranial Magnetic Stimulation (rTMS on Brain Functional Marker of Auditory Hallucinations in Schizophrenia Patients

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    Sonia Dollfus

    2013-04-01

    Full Text Available Several cross-sectional functional Magnetic Resonance Imaging (fMRI studies reported a negative correlation between auditory verbal hallucination (AVH severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS. Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS cluster, considered henceforward as a functional region of interest (fROI. After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities.

  16. Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates

    DEFF Research Database (Denmark)

    Large, I.; Bridge, H.; Ahmed, B.

    2016-01-01

    Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (s...

  17. Dopamine transporter 3'UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD

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    Polotskaia Anna

    2008-06-01

    Full Text Available Abstract Background Attention-Deficit/Hyperactivity Disorder (ADHD is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder. Methods To investigate the relationship between the dopamine transporter gene (SLC6A3 3'-UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning. Results Taking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009 and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III Freedom From Distractibility Index (F = 7.125, p = 0.008, as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026 and WISC-III Digit Span performance (F = 6.28, p = 0.023. Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected. Conclusion Results are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD.

  18. Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood

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    Trivin Christine

    2011-02-01

    Full Text Available Abstract Background It is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH and luteinizing hormone (LH are not informative and no spermogram can be done. Methods We classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH. Results Ten (26% boys had normal testicular function, 16 (42% had isolated tubular failure and 12 (32% also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B. Seven (21% girls had normal ovarian function, 11 (32% had partial and 16 (47% complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls. FSH and inhibin B were negatively correlated in boys (P Conclusion The concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.

  19. Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells.

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    Tatari-Calderone, Zohreh; Stojakovic, Milica; Dewan, Ramita; Le Bouder, Gama; Jankovic, Dragana; Vukmanovic, Stanislav

    2012-02-09

    Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62L(hi) T cells), T cells displayed CD3(low)CD5(hi) phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62L(hi) T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3(low)CD5(hi) phenotype, followed by a CD3(low)CD5(low) phenotype. Spleens of old mice with the CD3(low)/CD5(hi) T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self.

  20. Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells

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    Tatari-Calderone Zohreh

    2012-02-01

    Full Text Available Abstract Background Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. Results The phenotype of T cells from aged mice (18-24 months indicating functional TCR avidity (CD3 and CD5 expression correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62Lhi T cells, T cells displayed CD3lowCD5hi phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62Lhi T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3lowCD5hi phenotype, followed by a CD3lowCD5low phenotype. Spleens of old mice with the CD3low/CD5hi T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. Conclusions These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self.

  1. Voltage-Activated Calcium Channels as Functional Markers of Mature Neurons in Human Olfactory Neuroepithelial Cells: Implications for the Study of Neurodevelopment in Neuropsychiatric Disorders

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    Héctor Solís-Chagoyán

    2016-06-01

    Full Text Available In adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca2+ Channels (VACC is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor. The presence of channel-forming proteins in Olfactory Sensory Neurons (OSN was demonstrated by immunofluorescent labeling, and VACC functioning was assessed by microfluorometry and the patch-clamp technique. VACC were immunodetected only in OSN. Mature neurons responded to forskolin with a five-fold increase in Ca2+. By contrast, in precursor cells, a subtle response was observed. The involvement of VACC in the precursors’ response was discarded for the absence of transmembrane inward Ca2+ movement evoked by step depolarizations. Data suggest differential expression of VACC in neuronal cells depending on their developmental stage and also that the expression of these channels is acquired by OSN during maturation, to enable specialized functions such as ion movement triggered by membrane depolarization. The results support that VACC in OSN could be considered as a functional marker to study neurodevelopment.

  2. One step in-situ synthesis of amine functionalized graphene for immunosensing of cardiac marker cTnI.

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    Tuteja, Satish K; Kukkar, Manil; Suri, C R; Paul, A K; Deep, Akash

    2015-04-15

    2-Aminobenzyl amine (2-ABA) functionalized graphene is proposed for the ultrasensitive immunosensing of Cardiac Troponin I (cTnI). 2-ABA was electrochemically polymerized on the graphene decorated interdigitated electrode to obtain the amine functionalized graphene (f-GN). The f-GN electrode was then modified with monoclonal anti-cTnI antibodies via Schiff reaction based chemistry. Detailed characteristics of the processes involved and the finally developed antibody conjugated f-GN interdigitated electrode have been studied. The above micro-device was used in a drain source configuration for the sensing of cTnI. A wide dynamic linear range of antigen detection (0.01-1ng/mL) is achieved with the limit of detection of 0.01ng/mL. The utility of the proposed sensing technique is demonstrated by successfully testing the antigen concentration in spiked serum samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Near infrared (NIr) light increases expression of a marker of mitochondrial function in the mouse vestibular sensory epithelium.

    Science.gov (United States)

    Zhang, Lucy; Tung, Victoria W K; Mathews, Miranda; Camp, Aaron J

    2015-03-14

    Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and exercise. However, these approaches do not address the underlying causes of balance decline. Using mice, the impact of near infrared light (NIr) on the metabolism of cells in the vestibular sensory epithelium was assessed. Data collected shows that this simple and safe intervention may protect these vulnerable cells from the deleterious effects of natural aging. mRNA was extracted from the isolated peripheral vestibular sensory epithelium (crista ampullaris and utricular macula) and subsequently transcribed into a cDNA library. This library was then probed for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression was then used to quantify cellular metabolism. Using transcranial delivery of NIr in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90 sec/day for 5 days), this work suggests NIr alone may be sufficient to improve mitochondrial function in the vestibular sensory epithelium. Since there are currently no available, affordable, non-invasive methods of therapy to improve vestibular hair cell function, the application of external NIr radiation provides a potential strategy to counteract the impact of aging on cellular metabolism inthe vestibular sensory epithelium.

  4. Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular disease, all-cause mortality and deterioration in kidney function in persons with type 2 diabetes and microalbuminuria

    DEFF Research Database (Denmark)

    Zobel, Emilie H; von Scholten, Bernt Johan; Reinhard, Henrik

    2017-01-01

    for traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate). To assess if SDMA or ADMA improved risk prediction beyond traditional risk factors we calculated c statistics and relative integrated discrimination improvement (r......BACKGROUND: To evaluate symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) as risk markers of cardiovascular disease, all-cause mortality and deterioration in renal function in a well characterised type 2 diabetic population with microalbuminuria and without symptoms...... of coronary artery disease. METHODS: 200 participants followed for 6.1 years. SDMA and ADMA were measured at baseline. Endpoints included (1) composite cardiovascular endpoint (n = 40); (2) all-cause mortality (n = 26); and (3) decline in eGFR of >30% (n = 42). Cox models were unadjusted and adjusted...

  5. Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in rat model of ischemic-hypoxic brain injury

    Institute of Scientific and Technical Information of China (English)

    Liping Zhang; Liping Zou

    2008-01-01

    BACKGROUND: Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function, and these positive effects might be due to neural plasticity. OBJECTIVE: Myelin basic protein (MBP), microtubule-associated protein 2 (MAP2), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) were selected as markers of neural remodeling, and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment. DESIGN, TIME AND SETTING: A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007. MATERIALS: Twenty-four Sprague Dawley rat pups, aged 7 days, were selected for the present experiment. The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS: All animals were randomly divided into three groups: sham operation, model, and electro-acupuncture treatment, with 8 rats in each group. Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury. Upon model established, rats underwent hypobaric oxygen intervention for 24 hours. Only the left common carotid artery was exposed in rats of the sham operation group, without model establishment or oxygen intervention. The rats in the electro-acupuncture treatment group were treated with electro-acupuncture. One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint. The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second, as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second. Maximal current through the two dectrodes was limited to 3-5 mA. The stimulation lasted for 30 minutes per day for 2 weeks. Rats in the sham operation and model groups were not treated

  6. Neurohormones as markers of right- and left-sided cardiac dimensions and function in patients with untreated chronic heart failure

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Hildebrandt, Per; Appel, Jon;

    2005-01-01

    BACKGROUND: It is now well accepted that neuroendocrine activation is of pathophysiological and prognostic importance in patients with chronic heart failure (CHF). We hypothesized that the different neuroendocrine factors reflect different aspects of the cardiac dysfunction in CHF patients...... and that neuroendocrine profiling could be of value. In order to study this, we investigated the relationship between hormones and cardiac dimensions and function of both the right and left ventricle. METHODS: Twenty-three patients with newly diagnosed, untreated CHF were included. Right (RVEF) and left ventricular...

  7. Experimental coccidiosis influences the expression of the ABCB1 gene, a physiological important functional marker of intestinal integrity in chickens.

    Science.gov (United States)

    Haritova, Aneliya; Koinarski, Vencislav; Stanilova, Spaska

    2013-01-01

    Efflux transporters belonging to the family of ABC transporters have an important functional role in the maintenance of the intestinal barrier. As efflux transporters they prevent the absorption of toxic substances from feed, while at the same time facilitating the excretion of metabolic waste products as well as drugs from the circulation into the intestinal lumen. As Eimeria tenella infection significantly affects the integrity of caecum, the effects of experimental E. tenella infection on the levels of expression of ABCB1 mRNAs in the intestines and livers of broilers were evaluated. ABCB1 mRNA expression was quantified by qRT-PCR. Its expression levels were significantly down-regulated in the caecum of infected animals. The levels of ABCB1 mRNA were not changed in the duodenum and the liver. After treatment of the animals with sulfapyrazine for three days, not only a significant improvement of the clinical appearance but also a normalization of the P-gp expression was noticed. Although the current study cannot distinguish between the direct effect of the drug on the host and the drug action on the parasite, these results suggest that the treatment of coccidiosis with sulfachlorpyrazine also restored the expression of the investigated efflux transporter in the caecum. This is of clinical significance as P-glycoproteins contribute to the integrity of intestines and their function as important biological barriers, protecting poultry from pathogens and toxic compounds in animal feeds.

  8. Comparison of the effects of transdermal and oral rivastigmine on cognitive function and EEG markers in patients with Alzheimer's disease

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    Davide V Moretti

    2014-07-01

    Full Text Available Background: Alzheimer's disease (AD is the most common cause of dementia in older patients. Rivastigmine (RV, Exelon®, Novartis, a reversible cholinesterase inhibitor, improves clinical manifestations of AD and may enhance ACh-modulated electroencephalogram (EEG alpha frequency. This pilot study aimed to determine the effects of two formulations of RV (transdermal patch [TV-RDP] and oral capsules [TV-CP] on alpha frequency, in particular the posterior dominant rhythm, and cognitive function (assessed by the Mini-Mental State Examination [MMSE] in patients with AD.Methods: Subjects with AD were assigned to receive either RV-TDP 10 cm2 or RV-CP 12 mg/day. All patients underwent EEG recordings at the beginning and end of the 18-month study period using P3, P4, O1 and O2 electrodes, each at high (10.5–13.0 Hz and low (8.0–10.5 Hz frequency. MMSE scores were determined at the start of the study (T0 and at three successive 6-month intervals (T1, T2 and T3.Results: RV-TDP administration (n=10 maintained cognitive function as evidenced by stable MMSE scores from baseline to 18 months (21.07 ± 2.4 to 21.2 ± 3.1 compared with a decrease in MMSE score with RV-CP (n=10 over 18 months (18.3 ± 3.6 to 13.6 ± 5.06 [adjusted for covariates p=0.006]. MMSE scores were significantly different between treatment groups from 6 months (p=0.04. RV-TDP also increased the spectral power of alpha waves in the posterior region measured with electrode P3 in a significantly great percentage of patients than TV-CP from baseline to 18 months; 80% versus 30%, respectively (p=0.025 [χ2 test].Conclusion: RV-TDP was associated with a greater proportion of patients with increased posterior region alpha wave spectral power and significantly higher cognitive function at 18 months, compared with RV-CP treatment. Our findings suggest that RV-TDP provides an effective long-term management option in patients with AD compared with oral RV-CP. This study is a pilot, open

  9. Mass spectrometry profiling of oxysterols in human sperm identifies 25-hydroxycholesterol as a marker of sperm function

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    Chiara Zerbinati

    2017-04-01

    Full Text Available Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function.

  10. Putative RopGAPs impact division plane selection and interact with kinesin-12 POK1.

    Science.gov (United States)

    Stöckle, Dorothee; Herrmann, Arvid; Lipka, Elisabeth; Lauster, Theresa; Gavidia, Richard; Zimmermann, Steffi; Müller, Sabine

    2016-08-08

    Cell shape is defined by the surrounding cell walls in plants. Thus, spatial control over cell division planes and cell expansion polarity are essential to maintain cell morphology. In eukaryotes, cell polarity and expansion are controlled by Rho GTPase signalling, regulating cytoskeletal reorganization and vesicle trafficking(1). However, until now, Rho signalling was not implicated in mitotic events in plants. Here, we report a pair of putative Rho GTPase activating proteins (RhoGAPs) that interact with the mitosis-specific kinesin-12 POK1, a core component of the cortical division zone/site (CDZ/CDS) that is required for division plane maintenance in Arabidopsis(2-4). The designated pleckstrin homology GAPs (PHGAPs) are cytoplasmic and plasma membrane associated in interphase, but during mitosis they additionally localize to the CDZ/CDS in a POK-dependent manner. In contrast to pok1 pok2 mutants, phgap1 phgap2 double mutants show moderate cell wall positioning defects as a consequence of inaccurate positioning of the cortical division zone marker POK1. We conclude that loss of PHGAP function interferes with division plane selection in proliferative cell divisions.

  11. Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?

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    Yvonne Nussbaumer-Ochsner

    Full Text Available Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test, measurement of fractional exhaled nitric oxide (FeNO and pH/8-isoprostane in exhaled breath condensate (EBC. Lung tissue sections containing cancer-free large (LA and small airways (SA were stained for inflammatory cells. Mucosal (MCT respectively connective tissue mast cells (MCTC and interleukin-17A (IL-17A expression by mast cells was analysed using a double-staining protocol.The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances. IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39, for the FEV1% pred. (rs= 0.37 and for FEV1/FVC ratio (rs=0.38 with MCT in SA (P<0.05 for all instances. 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44, there was no correlation for pH or FeNO with cellular distribution in SA.Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the

  12. Development of unigene-derived SSR markers in cowpea (Vigna unguiculata) and their transferability to other Vigna species.

    Science.gov (United States)

    Gupta, S K; Gopalakrishna, T

    2010-07-01

    Unigene sequences available in public databases provide a cost-effective and valuable source for the development of molecular markers. In this study, the identification and development of unigene-based SSR markers in cowpea (Vigna unguiculata (L.) Walp.) is presented. A total of 1071 SSRs were identified in 15 740 cowpea unigene sequences downloaded from the National Center for Biotechnology Information. The most frequent SSR motifs present in the unigenes were trinucleotides (59.7%), followed by dinucleotides (34.8%), pentanucleotides (4%), and tetranucleotides (1.5%). The copy number varied from 6 to 33 for dinucleotide, 5 to 29 for trinucleotide, 5 to 7 for tetranucleotide, and 4 to 6 for pentanucleotide repeats. Primer pairs were successfully designed for 803 SSR motifs and 102 SSR markers were finally characterized and validated. Putative function was assigned to 64.7% of the unigene SSR markers based on significant homology to reported proteins. About 31.7% of the SSRs were present in coding sequences and 68.3% in untranslated regions of the genes. About 87% of the SSRs located in the coding sequences were trinucleotide repeats. Allelic variation at 32 SSR loci produced 98 alleles in 20 cowpea genotypes. The polymorphic information content for the SSR markers varied from 0.10 to 0.83 with an average of 0.53. These unigene SSR markers showed a high rate of transferability (88%) across other Vigna species, thereby expanding their utility. Alignment of unigene sequences with soybean genomic sequences revealed the presence of introns in amplified products of some of the SSR markers. This study presents the distribution of SSRs in the expressed portion of the cowpea genome and is the first report of the development of functional unigene-based SSR markers in cowpea. These SSR markers would play an important role in molecular mapping, comparative genomics, and marker-assisted selection strategies in cowpea and other Vigna species.

  13. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

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    Subhadra Nandakumar

    Full Text Available Mycobacterium bovis bacille Calmette-Guérin (BCG is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+ and CD8(+ T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+ and CD8(+ T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+ T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+ and CD8(+ T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  14. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Posey, James E; Amara, Rama Rao; Sable, Suraj B

    2014-01-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+) and CD8(+) T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+) and CD8(+) T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+) T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+) and CD8(+) T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  15. Micro- and nano-topography to enhance proliferation and sustain functional markers of donor-derived primary human corneal endothelial cells.

    Science.gov (United States)

    Muhammad, Rizwan; Peh, Gary S L; Adnan, Khadijah; Law, Jaslyn B K; Mehta, Jodhbir S; Yim, Evelyn K F

    2015-06-01

    One of the most common indications for corneal transplantation is corneal endothelium dysfunction, which can lead to corneal blindness. Due to a worldwide donor cornea shortage, alternative treatments are needed, but the development of new treatment strategies relies on the successful in vitro culture of primary human corneal endothelial cells (HCECs) because transformed cell lines and animal-derived corneal endothelial cells are not desirable for therapeutic applications. Primary HCECs are non-proliferative in vivo and challenging to expand in vitro while maintaining their characteristic cell morphology and critical markers. Biochemical cues such as growth factors and small molecules have been investigated to enhance the expansion of HCECs with a limited increase in proliferation. In this study, patterned tissue culture polystyrene (TCPS) was shown to significantly enhance the expansion of HCECs. The proliferation of HCECs increased up to 2.9-fold, and the expression amount and localization of cell-cell tight junction protein Zona Occludens-1 (ZO-1) was significantly enhanced when grown on 1 μm TCPS pillars. 250 nm pillars induced an optimal hexagonal morphology of HCEC cells. Furthermore, we demonstrated that the topographical effect on tight-junction expression and cell morphology could be maintained throughout each passage, and was effectively 'remembered' by the cells. Higher amount of tight-junction protein expression was maintained at cell junctions when topographic cues were removed in the successive seeding. This topographic memory suggested topography-exposed/induced cells would maintain the enhanced functional markers, which would be useful in cell-therapy based approaches to enable the in situ endothelial cell monolayer formation upon delivery. The development of patterned TCPS culture platforms could significantly benefit those researching human corneal endothelial cell cultivation for cell therapy, and tissue engineering applications.

  16. Comparison of Markers and Functional Attributes of Human Adipose-Derived Stem Cells and Dedifferentiated Adipocyte Cells from Subcutaneous Fat of an Obese Diabetic Donor.

    Science.gov (United States)

    Watson, James E; Patel, Niketa A; Carter, Gay; Moor, Andrea; Patel, Rekha; Ghansah, Tomar; Mathur, Abhishek; Murr, Michel M; Bickford, Paula; Gould, Lisa J; Cooper, Denise R

    2014-03-01

    Objective: Adipose tissue is a robust source of adipose-derived stem cells (ADSCs) that may be able to provide secreted factors that promote the ability of wounded tissue to heal. However, adipocytes also have the potential to dedifferentiate in culture to cells with stem cell-like properties that may improve their behavior and functionality for certain applications. Approach: ADSCs are adult mesenchymal stem cells that are cultured from the stromal vascular fraction of adipose tissue. However, adipocytes are capable of dedifferentiating into cells with stem cell properties. In this case study, we compare ADSC and dedifferentiated fat (DFAT) cells from the same patient and fat depot for mesenchymal cell markers, embryonic stem cell markers, ability to differentiate to adipocytes and osteoblasts, senescence and telomerase levels, and ability of conditioned media (CM) to stimulate migration of human dermal fibroblasts (HDFs). Innovation and Conclusions: ADSCs and DFAT cells displayed identical levels of CD90, CD44, CD105, and were CD34- and CD45-negative. They also expressed similar levels of Oct4, BMI1, KLF4, and SALL4. DFAT cells, however, showed higher efficiency in adipogenic and osteogenic capacity. Telomerase levels of DFAT cells were double those of ADSCs, and senescence declined in DFAT cells. CM from both cell types altered the migration of fibroblasts. Despite reports of ADSCs from a number of human depots, there have been no comparisons of the ability of dedifferentiated DFAT cells from the same donor and depot to differentiate or modulate migration of HDFs. Since ADSCs were from an obese diabetic donor, reprogramming of DFAT cells may help improve a patient's cells for regenerative medicine applications.

  17. Relationships among stressful life events and physiological markers, treatment adherence, and psychosocial functioning among youth with type 2 diabetes.

    Science.gov (United States)

    Walders-Abramson, Natalie; Venditti, Elizabeth M; Ievers-Landis, Carolyn E; Anderson, Barbara; El Ghormli, Laure; Geffner, Mitchell; Kaplan, Joan; Koontz, Michaela B; Saletsky, Ron; Payan, Marisa; Yasuda, Patrice

    2014-09-01

    To examine the relationships between stressful life events and physiological measures, adherence to prescribed oral medication regimens, depressive symptoms, and impaired quality of life (QoL) in adolescents with recent-onset type 2 diabetes (T2D). Data were collected from 497 ethnically diverse participants (66% female) in the final year of the Treatment Options for Type 2 Diabetes in Adolescents and Youth multicenter clinical trial. Exposure to 32 possible events over the previous year and rating of subsequent distress were collected by self-report and summarized as a major stressors score. This score was analyzed for relationship to glycemic control (hemoglobin A1c and treatment failure), body mass index, diagnosis of hypertension or triglyceride dyslipidemia, adherence to a prescribed oral medication regimen, presence of depressive symptoms, and impaired QoL. The total number of major stressful life events in the adolescents with T2D was calculated, with 33% reporting none, 67% reporting ≥ 1, 47% reporting ≥ 2, 33% reporting ≥ 3, and 20% reporting ≥ 4. There were no associations between the major stressors score and physiological measures or diagnosis of comorbidities. The odds of medication nonadherence increased significantly from those reporting ≥ 1 major stressor (OR, 1.58; P = .0265) to those reporting ≥ 4 major stressors (OR, 2.70; P = .0009). Significant odds of elevated depressive symptoms and impaired QoL were also found with increased reporting of major stressors. Exposure to major stressful life events is associated with lower adherence to prescribed oral medication regimens and impaired psychosocial functioning in adolescents with T2D. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Measurement of height velocity is an useful marker for monitoring pituitary function in patients who had traumatic brain injury.

    Science.gov (United States)

    Bellone, S; Einaudi, S; Caputo, M; Prodam, F; Busti, A; Belcastro, S; Parlamento, S; Zavattaro, M; Verna, F; Bondone, C; Tessaris, D; Gasco, V; Bona, G; Aimaretti, G

    2013-12-01

    To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale-GCS, Glasgow outcome scale-GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the "Regina Margherita" Hospital, in Turin and "Maggiore della Carità Hospital" in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

  19. EEG power asymmetry and functional connectivity as a marker of treatment effectiveness in DBS surgery for depression.

    Science.gov (United States)

    Quraan, Maher A; Protzner, Andrea B; Daskalakis, Zafiris J; Giacobbe, Peter; Tang, Chris W; Kennedy, Sidney H; Lozano, Andres M; McAndrews, Mary P

    2014-04-01

    whether EEG data were collected with active DBS or with the DBS stimulation turned off, suggesting stable functional and possibly structural modifications that may be attributed to plasticity.

  20. Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

    Science.gov (United States)

    The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

  1. SSR markers in transcripts of genes linked to post-transcriptional and transcriptional regulatory functions during vegetative and reproductive development of Elaeis guineensis.

    Science.gov (United States)

    Tranbarger, Timothy John; Kluabmongkol, Wanwisa; Sangsrakru, Duangjai; Morcillo, Fabienne; Tregear, James W; Tragoonrung, Somvong; Billotte, Norbert

    2012-01-03

    The oil palm (Elaeis guineensis Jacq.) is a perennial monocotyledonous tropical crop species that is now the world's number one source of edible vegetable oil, and the richest dietary source of provitamin A. While new elite genotypes from traditional breeding programs provide steady yield increases, the long selection cycle (10-12 years) and the large areas required to cultivate oil palm make genetic improvement slow and labor intensive. Molecular breeding programs have the potential to make significant impacts on the rate of genetic improvement but the limited molecular resources, in particular the lack of molecular markers for agronomic traits of interest, restrict the application of molecular breeding schemes for oil palm. In the current study, 6,103 non-redundant ESTs derived from cDNA libraries of developing vegetative and reproductive tissues were annotated and searched for simple sequence repeats (SSRs). Primer pairs from sequences flanking 289 EST-SSRs were tested to detect polymorphisms in elite breeding parents and their crosses. 230 of these amplified PCR products, 88 of which were polymorphic within the breeding material tested. A detailed analysis and annotation of the EST-SSRs revealed the locations of the polymorphisms within the transcripts, and that the main functional category was related to transcription and post-transcriptional regulation. Indeed, SSR polymorphisms were found in sequences encoding AP2-like, bZIP, zinc finger, MADS-box, and NAC-like transcription factors in addition to other transcriptional regulatory proteins and several RNA interacting proteins. The identification of new EST-SSRs that detect polymorphisms in elite breeding material provides tools for molecular breeding strategies. The identification of SSRs within transcripts, in particular those that encode proteins involved in transcriptional and post-transcriptional regulation, will allow insight into the functional roles of these proteins by studying the phenotypic traits

  2. Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: a cross-sectional study.

    Science.gov (United States)

    Shiozawa, Nobuyoshi; Hayashimoto, Kanae; Suzuki, Etsuji; Kikuchi, Hiroshi; Takata, Shingo; Ashida, Kozo; Watanabe, Masutaka; Hosaki, Yasuhiro; Mitsunobu, Fumihiro

    2010-08-09

    Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

  3. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure.

    Science.gov (United States)

    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa

    2016-01-01

    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  4. Effect of Dietary Intake of Avocado Oil and Olive Oil on Biochemical Markers of Liver Function in Sucrose-Fed Rats

    Directory of Open Access Journals (Sweden)

    Octavio Carvajal-Zarrabal

    2014-01-01

    Full Text Available Metabolic changes, along with cardiovascular and hepatic factors, are associated with the development of diseases such as diabetes, dyslipidemia, and obesity. We evaluated the effect of avocado oil supplementation (centrifuged and solvent extracted, compared with olive oil, upon the hepatic function in sucrose-fed rats. Twenty-five rats were divided into five groups: control (basal diet, a sucrose-fed group (basal diet plus 30% sucrose solution, and three other groups (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS, resp.. Glucose, total cholesterol, triglycerides, total protein, albumin, globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, cholinesterase, and α-amylase concentrations were determined and avocado oil effect on them was studied. In some cases the induced metabolic alteration significantly affected total protein and bilirubin levels and also had a highly significant effect on α-amylase levels. AOC and AOS exhibited effects similar to those of olive oil, according to the nonsignificant difference in fatty acid profile observed by other authors. Avocado oil consumption could be beneficial in the control of altered metabolic profile illnesses as it presents effects on hepatic function biochemical markers similar to olive oil.

  5. Effect of dietary intake of avocado oil and olive oil on biochemical markers of liver function in sucrose-fed rats.

    Science.gov (United States)

    Carvajal-Zarrabal, Octavio; Nolasco-Hipolito, Cirilo; Aguilar-Uscanga, Ma Guadalupe; Melo Santiesteban, Guadalupe; Hayward-Jones, Patricia M; Barradas-Dermitz, Dulce Ma

    2014-01-01

    Metabolic changes, along with cardiovascular and hepatic factors, are associated with the development of diseases such as diabetes, dyslipidemia, and obesity. We evaluated the effect of avocado oil supplementation (centrifuged and solvent extracted), compared with olive oil, upon the hepatic function in sucrose-fed rats. Twenty-five rats were divided into five groups: control (basal diet), a sucrose-fed group (basal diet plus 30% sucrose solution), and three other groups (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS, resp.). Glucose, total cholesterol, triglycerides, total protein, albumin, globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, cholinesterase, and α -amylase concentrations were determined and avocado oil effect on them was studied. In some cases the induced metabolic alteration significantly affected total protein and bilirubin levels and also had a highly significant effect on α -amylase levels. AOC and AOS exhibited effects similar to those of olive oil, according to the nonsignificant difference in fatty acid profile observed by other authors. Avocado oil consumption could be beneficial in the control of altered metabolic profile illnesses as it presents effects on hepatic function biochemical markers similar to olive oil.

  6. Transcriptional regulators transforming growth factor-β1 and estrogen-related receptor-α identified as putative mediators of calf rumen epithelial tissue development and function during weaning.

    Science.gov (United States)

    Connor, E E; Baldwin, R L; Walker, M P; Ellis, S E; Li, C; Kahl, S; Chung, H; Li, R W

    2014-07-01

    Molecular mechanisms regulating rumen epithelial development remain largely unknown. To identify gene networks and regulatory factors controlling rumen development, Holstein bull calves (n=18) were fed milk replacer only (MRO) until 42 d of age. Three calves each were euthanized at 14 and 42 d of age for tissue collection to represent preweaning, and the remaining calves were provided diets of either milk replacer + orchard grass hay (MH; n=6) to initiate weaning without development of rumen papillae, or milk replacer + calf starter (MG; n=6) to initiate weaning and development of rumen papillae. At 56 and 70 d of age, 3 calves from the MH and MG groups were euthanized for collection of rumen epithelium. Total RNA and protein were extracted for microarray analysis and to validate detected changes in selected protein expression, respectively. As expected, calves fed MRO had no rumen papillae and development of papillae was greater in MG versus MH calves. Differentially expressed genes between the MRO diet at d 42 (preweaning) versus the MG or MH diets at d 56 (during weaning) were identified using permutation analysis of differential expression. Expression of 345 and 519 transcripts was uniquely responsive to MG and MH feeding, respectively. Ingenuity Pathway Analysis (Qiagen, Redwood City, CA) indicated that the top-ranked biological function affected by the MG diet was the cell cycle, and TFGB1, FBOX01, and PPARA were identified as key transcriptional regulators of genes responsive to the MG diet and associated with development of rumen papillae. Increased expressions of TGFB1 mRNA and protein in response to the MG diet were confirmed by subsequent analyses. The top-ranking biological function affected by the MH diet was energy production. Receptors for IGF-1 and insulin, ESRRA, and PPARD were identified by ingenuity pathway analysis as transcriptional regulators of genes responsive to the MH diet. Further analysis of TGFB1 and ESRRA mRNA expression in rumen

  7. Biochemical markers of bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-08-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

  8. Genome wide characterization of short tandem repeat markers in sweet orange (Citrus sinensis.

    Directory of Open Access Journals (Sweden)

    Manosh Kumar Biswas

    Full Text Available Sweet orange (Citrus sinensis is one of the major cultivated and most-consumed citrus species. With the goal of enhancing the genomic resources in citrus, we surveyed, developed and characterized microsatellite markers in the ≈347 Mb sequence assembly of the sweet orange genome. A total of 50,846 SSRs were identified with a frequency of 146.4 SSRs/Mbp. Dinucleotide repeats are the most frequent repeat class and the highest density of SSRs was found in chromosome 4. SSRs are non-randomly distributed in the genome and most of the SSRs (62.02% are located in the intergenic regions. We found that AT-rich SSRs are more frequent than GC-rich SSRs. A total number of 21,248 SSR primers were successfully developed, which represents 89 SSR markers per Mb of the genome. A subset of 950 developed SSR primer pairs were synthesized and tested by wet lab experiments on a set of 16 citrus accessions. In total we identified 534 (56.21% polymorphic SSR markers that will be useful in citrus improvement. The number of amplified alleles ranges from 2 to 12 with an average of 4 alleles per marker and an average PIC value of 0.75. The newly developed sweet orange primer sequences, their in silico PCR products, exact position in the genome assembly and putative function are made publicly available. We present the largest number of SSR markers ever developed for a citrus species. Almost two thirds of the markers are transferable to 16 citrus relatives and may be used for constructing a high density linkage map. In addition, they are valuable for marker-assisted selection studies, population structure analyses and comparative genomic studies of C. sinensis with other citrus related species. Altogether, these markers provide a significant contribution to the citrus research community.

  9. Genome wide characterization of short tandem repeat markers in sweet orange (Citrus sinensis).

    Science.gov (United States)

    Biswas, Manosh Kumar; Xu, Qiang; Mayer, Christoph; Deng, Xiuxin

    2014-01-01

    Sweet orange (Citrus sinensis) is one of the major cultivated and most-consumed citrus species. With the goal of enhancing the genomic resources in citrus, we surveyed, developed and characterized microsatellite markers in the ≈347 Mb sequence assembly of the sweet orange genome. A total of 50,846 SSRs were identified with a frequency of 146.4 SSRs/Mbp. Dinucleotide repeats are the most frequent repeat class and the highest density of SSRs was found in chromosome 4. SSRs are non-randomly distributed in the genome and most of the SSRs (62.02%) are located in the intergenic regions. We found that AT-rich SSRs are more frequent than GC-rich SSRs. A total number of 21,248 SSR primers were successfully developed, which represents 89 SSR markers per Mb of the genome. A subset of 950 developed SSR primer pairs were synthesized and tested by wet lab experiments on a set of 16 citrus accessions. In total we identified 534 (56.21%) polymorphic SSR markers that will be useful in citrus improvement. The number of amplified alleles ranges from 2 to 12 with an average of 4 alleles per marker and an average PIC value of 0.75. The newly developed sweet orange primer sequences, their in silico PCR products, exact position in the genome assembly and putative function are made publicly available. We present the largest number of SSR markers ever developed for a citrus species. Almost two thirds of the markers are transferable to 16 citrus relatives and may be used for constructing a high density linkage map. In addition, they are valuable for marker-assisted selection studies, population structure analyses and comparative genomic studies of C. sinensis with other citrus related species. Altogether, these markers provide a significant contribution to the citrus research community.

  10. CRYSTAL STRUCTURE ANALYSIS OF A PUTATIVE OXIDOREDUCTASE FROM KLEBSIELLA PNEUMONIAE

    Energy Technology Data Exchange (ETDEWEB)

    Baig, M.; Brown, A.; Eswaramoorthy, S.; Swaminathan, S.

    2009-01-01

    Klebsiella pneumoniae, a gram-negative enteric bacterium, is found in nosocomial infections which are acquired during hospital stays for about 10% of hospital patients in the United States. The crystal structure of a putative oxidoreductase from K. pneumoniae has been determined. The structural information of this K. pneumoniae protein was used to understand its function. Crystals of the putative oxidoreductase enzyme were obtained by the sitting drop vapor diffusion method using Polyethylene glycol (PEG) 3350, Bis-Tris buffer, pH 5.5 as precipitant. These crystals were used to collect X-ray data at beam line X12C of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL). The crystal structure was determined using the SHELX program and refi ned with CNS 1.1. This protein, which is involved in the catalysis of an oxidation-reduction (redox) reaction, has an alpha/beta structure. It utilizes nicotinamide adenine dinucleotide phosphate (NADP) or nicotine adenine dinucleotide (NAD) to perform its function. This structure could be used to determine the active and co-factor binding sites of the protein, information that could help pharmaceutical companies in drug design and in determining the protein’s relationship to disease treatment such as that for pneumonia and other related pathologies.

  11. Age and markers of Leydig cell function, but not of Sertoli cell function predict the success of sperm retrieval in adolescents and adults with Klinefelter's syndrome.

    Science.gov (United States)

    Rohayem, J; Fricke, R; Czeloth, K; Mallidis, C; Wistuba, J; Krallmann, C; Zitzmann, M; Kliesch, S

    2015-09-01

    Microsurgical testicular sperm extraction (mTESE), combined with intracytoplasmic sperm injection (ICSI) represents a chance for azoospermic men with Klinefelter's syndrome (KS) to father children. The objective of this study was to identify predictive factors for the success of mTESE from adolescents and adults with KS. The clinical data of 50 late pubertal adolescents (13-19 years) and 85 adult patients (20-61 years) with non-mosaic KS, who underwent mTESE, were analysed with respect to factors, potentially predictive of active spermatogenesis; specifically a history of cryptorchidism, age, testicular volumes, serum levels of LH, FSH, testosterone (T) and estradiol at the time of surgery. Inhibin B, AMH and INSL3 were additionally analysed in the adolescents. A younger age and a near-compensated Leydig cell function were associated with higher success of sperm retrieval via mTESE: In adolescents ≥15-19 years, spermatozoa were retrieved in 45%, compared to 31% in adults; in adolescents aged 13-14 years, spermatozoa were collected in only 10%. Adolescents with an LH ≤17.5 U/L, along with a T level ≥7.5 nmol/L had the best success rate (54%), which fell to 44% with higher LH, whereas those with low T (history of cryptorchidism was associated with lower retrieval rates. A window of opportunity for an approximate 50% chance to retrieve spermatozoa via mTESE exists for young, late pubertal KS patients between age 15 and young adulthood, when Leydig cell function is at its best. In these cases, referral to a centre of expertise should be considered.

  12. Functional expression of a putative geraniol 8-hydroxylase by reconstitution of bacterially expressed plant CYP76F45 and NADPH-cytochrome P450 reductase CPR I from Croton stellatopilosus Ohba.

    Science.gov (United States)

    Sintupachee, Siriluk; Promden, Worrawat; Ngamrojanavanich, Nattaya; Sitthithaworn, Worapan; De-Eknamkul, Wanchai

    2015-10-01

    While attempting to isolate the enzyme geranylgeraniol 18-hydroxylase, which is involved in plaunotol biosynthesis in Croton stellatopilosus (Cs), the cDNAs for a cytochrome P450 monooxygenase(designated as CYP76F45) and an NADPH-cytochrome P450 reductase (designated as CPR I based on its classification) were isolated from the leaf. The CYP76F45 and CsCPR I genes have open reading frames (ORFs) encoding 507- and 711-amino acid proteins with predicted relative molecular weights of 56.7 and 79.0 kDa,respectively. Amino acid sequence comparison showed that both CYP76F45 (63–73%) and CsCPR I (79–83%) share relatively high sequence identities with homologous proteins in other plant species.Phylogenetic tree analysis confirmed that CYP76F45 belongs to the CYP76 family and that CsCPR I belongs to Class I of dicotyledonous CPRs, with both being closely related to Ricinus communis genes. Functional characterization of both enzymes, each expressed separately in Escherichia coli as recombinant proteins,showed that only simultaneous incubation of the membrane bound proteins with the substrate geraniol (GOH) and the coenzyme NADPH could form 8-hydroxygeraniol. The enzyme mixture could also utilize acyclic sesquiterpene farnesol (FOH) with a comparable substrate preference ratio (GOH:FOH) of 54:46. The levelsof the CYP76F45 and CsCPR I transcripts in the shoots, leaves and twigs of C. stellatopilosus were correlated with the levels of a major monoterpenoid indole alkaloid, identified tentatively as 19-Evallesamine,that accumulated in these plant parts. These results suggested that CYP76F45 and CPR I function as the enzyme geraniol-8-hydroxylase (G8H), which is likely to be involved in the biosynthesis of the indole alkaloid in C. stellatopilosus [corrected].

  13. Peripheral markers of thyroid function

    DEFF Research Database (Denmark)

    Schmidt, Ulla; Nygaard, Birte; Winther Jensen, Ebbe

    2013-01-01

    the combination therapy. HYPOTHESIS: Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy. METHODS: Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT...

  14. The effect of Citrus Aurantifolia (Lemon) peels on cardiometabolic risk factors and markers of endothelial function in adolescents with excess weight: A triple-masked randomized controlled trial.

    Science.gov (United States)

    Hashemipour, Mahin; Kargar, Maryam; Ghannadi, Alireza; Kelishadi, Roya

    2016-01-01

    Background: Childhood obesity is becoming a global problem and its incidence is increasing. The role of dietary intervention with fruits containing vitamin C and flavonoid to control obesity consequences in childhood has not been yet defined. Lemon (Citrus aurantifolia) peels contain flavonoid, pectin and vitamin C. We aimed to compare the effects of lemon peels and placebo on cardiometabolic risk factors and markers of endothelial function among adolescents with overweight and obesity. Methods: In this triple-masked, randomized controlled trial, 60 overweight/obese adolescents were enrolled in a 4-week trial. Eligible participants were randomly assigned into two groups of equal number receiving daily oral capsules containing lemon powder or placebo. Fasting blood sugar, lipid profile, ICAM-1 and VCAM-1, as well as systolic and diastolic blood pressure were compared between the two groups before and after administration of medication and placebo. Results: Of the total 60 enrolled patients, 30 and 29 patients in the lemon and control groups completed the study, respectively. The results of within-group analysis demonstrated a slight reduction in body mass index, LDL-C and systolic blood pressure in the lemon group, but no between group differences existed in the studied variables. Conclusion: This study revealed that consumption of lemon peel extract has some beneficial effects for childhood obesity; however, no considerable effect was documented on anthropometric measures and biochemical factors. Future studies with longer follow up are highly recommended.

  15. Effects of N-acetyl-L-cysteine on redox status and markers of renal function in mice inoculated with Bothrops jararaca and Crotalus durissus terrificus venoms.

    Science.gov (United States)

    Barone, Juliana Marton; Frezzatti, Rodrigo; Silveira, Paulo Flavio

    2014-03-01

    Renal dysfunction is an important aggravating factor in accidents caused by Crotalus durissus terrificus (Cdt) and Bothrops jararaca (Bj) bites. N-acetyl-l-cysteine (NAC) is well known as a nephroprotective antioxidant with low toxicity. The present study investigated the effects of NAC on redox status and markers of renal function in mice that received vehicle (controls) or venoms (v) of Cdt and Bj. In controls NAC promoted hypercreatinemia, hypouremia, hyperosmolality with decreased urea in urine, hyperproteinuria, decreased protein and increased dipeptidyl peptidase IV (DPPIV) in membrane-bound fraction (MF) from renal cortex (RC) and medulla (RM). NAC ameliorated or normalized altered creatinuria, proteinemia and aminopeptidase (AP) acid in MF, AP basic (APB) in soluble fraction (SF), and neutral AP in SF and MF from RC and RM in vBj envenomation. NAC ameliorated or normalized altered neutral AP in SF from RC and RM, and DPPIV and protein in MF from RC in vCdt envenomation. NAC ameliorated or restored renal redox status respectively in vCdt and vBj, and normalized uricemia in both envenomations. These data are promising perspectives that recommend the clinical evaluation of NAC as potential coadjuvant in the anti venom serotherapy for accidents with these snake's genera.

  16. Cloning of a conserved receptor-like protein kinase gene and its use as a functional marker for homoeologous group-2 chromosomes of the triticeae species.

    Directory of Open Access Journals (Sweden)

    Bi Qin

    Full Text Available Receptor-like kinases (RLKs play broad biological roles in plants. We report on a conserved receptor-like protein kinase (RPK gene from wheat and other Triticeae species. The TaRPK1 was isolated from the Triticum aestivum cv. Prins - Triticum timopheevii introgression line IGVI-465 carrying the powdery mildew resistance gene Pm6. The TaRPK1 was mapped to homoeologous chromosomes 2A (TaRPK1-2A, 2D (TaRPK1-2D and the Pm6-carrier chromosome 2G (TaRPK1-2G of IGVI-465. Under the tested conditions, only the TaRPK1-2G allele was actively transcribed, producing two distinct transcripts via alternative splicing. The predicted 424-amino acid protein of TaRPK1-2G contained a signal peptide, a transmembrane domain and an intracellular serine/threonine kinase domain, but lacked a typical extracellular domain. The expression of TaRPK1-2G gene was up-regulated upon the infection by Blumeria graminis f.sp. tritici (Bgt and treatment with methyl jasmonate (MeJA, but down-regulated in response to treatments of SA and ABA. Over-expression of TaRPK1-2G in the powdery mildew susceptible wheat variety Prins by a transient expression assay showed that it slightly reduced the haustorium index of the infected Bgt. These data indicated that TaRPK1-2G participated in the defense response to Bgt infection and in the JA signaling pathway. Phylogenetic analysis indicated that TaRPK1-2G was highly conserved among plant species, and the amino acid sequence similarity of TaRPK1-2G among grass species was more than 86%. Based on its conservation, the RPK gene-based STS primers were designed, and used to amplify the RPK orthologs from the homoeologous group-2 chromosomes of all the tested Triticeae species, such as chromosome 2G of T. timopheevii, 2R of Secale cereale, 2H of Hordeum vulgare, 2S of Aegilops speltoides, 2S(l of Ae. longissima, 2M(g of Ae. geniculata, 2S(p and 2U(p of Ae. peregrina. The developed STS markers serve as conserved functional markers for the

  17. Is hand bone mineral density a marker for hand function in patients with established rheumatoid arthritis? The correlation among bone mineral density of the hand, radiological findings and hand function.

    Science.gov (United States)

    Dogu, Beril; Kuran, Banu; Yilmaz, Figen; Usen, Ahmet; Sirzai, Hulya

    2013-08-01

    The objective of this study is to assess the role of hand bone mineral density (BMD) as a prospective marker for hand function and the correlation of hand BMD with X-ray findings and hand functioning in patients with established rheumatoid arthritis (RA). Eighty-three female patients diagnosed with RA were enrolled. All BMD measurements were performed on both hands. The radiological evaluation was conducted according to the van der Heijde modification of the Sharp method (Sharp/van der Heijde). Duruöz Hand Index (DHI) was used to establish the disability in the hands. Furthermore, handgrip strength (HGS), pinch strength (PS), lateral pinch (LP), tip-to-tip pinch (TTP) and three-fingered pinch (TFP) on both the dominant and the non-dominant hands was measured. A significant positive correlation between hand BMD and HGS as well as all PSs with p DHI (p > 0.05). The hand BMD and the Sharp/van der Heijde scores were significantly in reverse correlation (p DHI-related variants, HGS and PS and the total DHI scores were reversely correlated, while there was a positive significant association with radiological scores (p DHI, HGS, LP, TTP, TFP and radiographic total scores. Our study demonstrated that a one-off hand BMD measurement failed to adequately indicate a loss in hand function as measured by DHI. Ultimately, HGS and TTP were shown to be the most effective indicators for measuring hand functions.

  18. Ornithine cyclodeaminase/μ-crystallin homolog from the hyperthermophilic archaeon Thermococcus litoralis functions as a novel Δ1-pyrroline-2-carboxylate reductase involved in putative trans-3-hydroxy-l-proline metabolism

    Directory of Open Access Journals (Sweden)

    Seiya Watanabe

    2014-01-01

    Full Text Available l-Ornithine cyclodeaminase (OCD is involved in l-proline biosynthesis and catalyzes the unique deaminating cyclization of l-ornithine to l-proline via a Δ1-pyrroline-2-carboxyrate (Pyr2C intermediate. Although this pathway functions in only a few bacteria, many archaea possess OCD-like genes (proteins, among which only AF1665 protein (gene from Archaeoglobus fulgidus has been characterized as an NAD+-dependent l-alanine dehydrogenase (AfAlaDH. However, the physiological role of OCD-like proteins from archaea has been unclear. Recently, we revealed that Pyr2C reductase, involved in trans-3-hydroxy-l-proline (T3LHyp metabolism of bacteria, belongs to the OCD protein superfamily and catalyzes only the reduction of Pyr2C to l-proline (no OCD activity [FEBS Open Bio (2014 4, 240–250]. In this study, based on bioinformatics analysis, we assumed that the OCD-like gene from Thermococcus litoralis DSM 5473 is related to T3LHyp and/or proline metabolism (TlLhpI. Interestingly, TlLhpI showed three different enzymatic activities: AlaDH; N-methyl-l-alanine dehydrogenase; Pyr2C reductase. Kinetic analysis suggested strongly that Pyr2C is the preferred substrate. In spite of their similar activity, TlLhpI had a poor phylogenetic relationship to the bacterial and mammalian reductases for Pyr2C and formed a close but distinct subfamily to AfAlaDH, indicating convergent evolution. Introduction of several specific amino acid residues for OCD and/or AfAlaDH by site-directed mutagenesis had marked effects on both AlaDH and Pyr2C reductase activities. The OCC_00387 gene, clustered with the TlLhpI gene on the genome, encoded T3LHyp dehydratase, homologous to the bacterial and mammalian enzymes. To our knowledge, this is the first report of T3LHyp metabolism from archaea.

  19. Ten Putative Contributors to the Obesity Epidemic

    Science.gov (United States)

    McAllister, Emily J.; Dhurandhar, Nikhil V.; Keith, Scott W.; Aronne, Louis J.; Barger, Jamie; Baskin, Monica; Benca, Ruth M.; Biggio, Joseph; Boggiano, Mary M.; Eisenmann, Joe C.; Elobeid, Mai; Fontaine, Kevin R.; Gluckman, Peter; Hanlon, Erin C.; Katzmarzyk, Peter; Pietrobelli, Angelo; Redden, David T.; Ruden, Douglas M.; Wang, Chenxi; Waterland, Robert A.; Wright, Suzanne M.; Allison, David B.

    2010-01-01

    The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic. PMID:19960394

  20. Serotonin, neural markers, and memory

    OpenAIRE

    Alfredo eMeneses

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The i...

  1. Cloning and Functional Marker of GDH1 Gene in Wheat%小麦 GDH1基因克隆及其功能标记开发

    Institute of Scientific and Technical Information of China (English)

    李冰; 张照贵; 王佳佳; 李斯深

    2014-01-01

    Glutamate dehydrogenase ( GDH ) is an enzyme catalyzing a reversible reaction of compoun-ding L-glutamate.Assimilation of ammonia via GDH is more energy -efficient than that via glutamate syn-thase .GDH1 gene was the dominant form in most of examined tissues , perhaps suggesting its greater functional significance than other GDH genes.In this study, the genomic sequence on chromosome A , B and D of a no-vel gene, designated TaGDH1, was isolated from the hexaploid wheat ( Triticum aestivum L.) genome data-bases .An InDel marker was designed based on the insert /deletion divergence in the 1 900~1 983 bp position of TaGDH1a gene sequence, and was located on the chromosome 5A in wheat.%谷氨酸脱氢酶( glutamate dehydrogenase , GDH)在植物体内催化合成谷氨酸的可逆反应,通过GDH固氮比谷氨酸合成酶途径更节省能量。在植物大多数组织中,GDH1是该基因家族中表达最高的基因,比其他GDH成员具有更为重要的作用。本研究从普通小麦基因组中分离了TaGDH1基因在A、B、D染色体组的序列。针对TaGDH1 a基因在基因组DNA序列1900~1983 bp位置存在的核苷酸差异设计了一个插入/缺失标记,同时将该标记定位在5A染色体上。

  2. Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist

    Directory of Open Access Journals (Sweden)

    Neutzsky-Wulff Anita V

    2012-10-01

    Full Text Available Abstract Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM, and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c. Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass. As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths. Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.

  3. Functional characterisation of a putative rhamnogalacturonan II specific xylosyltransferase

    DEFF Research Database (Denmark)

    Madsen, Jack Egelund; Damager, Iben; Faber, Kirsten;

    2008-01-01

    An Arabidopsis thaliana gene, At1g56550, was expressed in Pichia pastoris and the recombinant protein was shown to catalyse transfer of d-xylose from UDP-alpha-d-xylose onto methyl alpha-l-fucoside. The product formed was shown by 1D and 2D (1)H NMR spectroscopy to be Me alpha-d-Xyl-(1,3)-alpha...

  4. Functional characterisation of a putative rhamnogalacturonan II specific xylosyltransferase.

    Science.gov (United States)

    Egelund, Jack; Damager, Iben; Faber, Kirsten; Olsen, Carl-Erik; Ulvskov, Peter; Petersen, Bent Larsen

    2008-09-22

    An Arabidopsis thaliana gene, At1g56550, was expressed in Pichia pastoris and the recombinant protein was shown to catalyse transfer of D-xylose from UDP-alpha-D-xylose onto methyl alpha-L-fucoside. The product formed was shown by 1D and 2D 1H NMR spectroscopy to be Me alpha-D-Xyl-(1,3)-alpha-L-Fuc, which is identical to the proposed target structure in the A-chain of rhamnogalacturonan II. Chemically synthesized methyl L-fucosides derivatized by methyl groups on either the 2-, 3- or 4 position were tested as acceptor substrates but only methyl 4-O-methyl-alpha-L-fucopyranoside acted as an acceptor, although to a lesser extent than methyl alpha-L-fucoside. At1g56550 is suggested to encode a rhamnogalacturonan II specific xylosyltransferase.

  5. Functional analysis of nine putative chemoreceptor proteins in Sinorhizobium meliloti.

    Science.gov (United States)

    Meier, Veronika M; Muschler, Paul; Scharf, Birgit E

    2007-03-01

    The genome of the symbiotic soil bacterium Sinorhizobium meliloti contains eight genes coding for methyl-accepting chemotaxis proteins (MCPs) McpS to McpZ and one gene coding for a transducer-like protein, IcpA. Seven of the MCPs are localized in the cytoplasmic membrane via two membrane-spanning regions, whereas McpY and IcpA lack such hydrophobic regions. The periplasmic regions of McpU, McpV, and McpX contain the small-ligand-binding domain Cache. In addition, McpU possesses the ligand-binding domain TarH. By probing gene expression with lacZ fusions, we have identified mcpU and mcpX as being highly expressed. Deletion of any one of the receptor genes caused impairments in the chemotactic response toward most organic acids, amino acids, and sugars in a swarm plate assay. The data imply that chemoreceptor proteins in S. meliloti can sense more than one class of carbon source and suggest that many or all receptors work as an ensemble. Tactic responses were virtually eliminated for a strain lacking all nine receptor genes. Capillary assays revealed three important sensors for the strong attractant proline: McpU, McpX, and McpY. Receptor deletions variously affected free-swimming speed and attractant-induced chemokinesis. Noticeably, cells lacking mcpU were swimming 9% slower than the wild-type control. We infer that McpU inhibits the kinase activity of CheA in the absence of an attractant. Cells lacking one of the two soluble receptors were impaired in chemokinetic proficiency by more than 50%. We propose that the internal sensors, IcpA and the PAS domain containing McpY, monitor the metabolic state of S. meliloti.

  6. Putative Nitrogen Sensing Systems in Higher Plants

    Institute of Scientific and Technical Information of China (English)

    Hon-Ming Lam; Ying Ann Chiao; Man-Wah Li; Yuk-Kwong Yung; Sang Ji

    2006-01-01

    Nitrogen (N) metabolism is essential for the biosynthesis of vital biomolecules. N status thus exerts profound effects on plant growth and development, and must be closely monitored. In bacteria and fungi, a few sophisticated N sensing systems have been extensively studied. In animals, the ability to receive amino acid signals has evolved to become an integral part of the nervous coordination system. In this review, we will summarize recent developments in the search for putative N sensing systems in higher plants based on homologous systems in bacteria, fungi, and animals. Apparently, although plants have separated and diversified from other organisms during the evolution process, striking similarities can be found in their N sensing systems compared with those of their counterparts; however, our understanding of these systems is still incomplete. Significant modifications of the N sensing systems (including cross-talk with other signal transduction pathways) in higher plants may be a strategy of adaptation to their unique mode of life.

  7. Putative respiratory chain of Porphyromonas gingivalis.

    Science.gov (United States)

    Meuric, Vincent; Rouillon, Astrid; Chandad, Fatiha; Bonnaure-Mallet, Martine

    2010-05-01

    The electron transfer chain in Porphyromonas gingivalis, or periodontopathogens, has not yet been characterized. P. gingivalis, a strict anaerobic bacteria and the second colonizer of the oral cavity, is considered to be a major causal agent involved in periodontal diseases. Primary colonizers create a favorable environment for P. gingivalis growth by decreasing oxygen pressure. Oxygen does not appear to be the final electron acceptor of the respiratory chain. Fumarate and cytochrome b have been implicated as major components of the respiratory activity. However, the P. gingivalis genome shows many other enzymes that could be implicated in aerobic or nitrite respiration. Using bioinformatic tools and literature studies of respiratory pathways, the ATP synthesis mechanism from the sodium cycle and nutrients metabolism, the putative respirasome of P. gingivalis has been proposed.

  8. Distribution of genes associated with yield potential and water-saving in Chinese Zone II wheat detected by developed functional markers

    Indian Academy of Sciences (India)

    Zhenxian Gao; Zhanliang Shi; Aimin Zhang; Jinkao Guo

    2015-03-01

    Functional markers (FMs) developed from sequence polymorphisms are present in allelic variants of a functional gene at a locus and are directly associated with phenotypic variations. In this study, FM linked to Rht-B1, Rht-D1, TaCwi-A1, TaSus2-2B, TaGW2-6A and Dreb-B1 genes conferring to yield potential and water-saving were selected to analyse the distribution in 102 wheat varieties, most of which were authorized in the past decade and adapted to grow in Zone II of China. First, the semi-dwarfing genes Rht-B1b and Rht-D1b (mutant alleles) conferring to grain yield were analysed. The frequencies of favourable alleles Rht-B1b and Rht-D1b were 32.4 and 58.8%, respectively. Comparing with the previous report, the frequency of Rht-B1b among cultivars in this study is similar to the frequency among cultivars released in the 1990s, while the frequency of Rht-D1b is slightly lower than the previous report 63.9%. Twelve (11.8%) cultivars neither contained Rht-B1b nor Rht-D1b, while only Yumai 66 contained both semidwarfing genes. Linyuan8 and Xinong 928 are heterozygous at RhtB1 locus and Zhengmai 9023 is heterozygous at both RhtB1 and Rht-D1 loci. Second, the TaCwi-A1, TaSus2-2B and TaGW2-6A genes considered as candidate genes related to grain weight were detected. We found that the frequencies of the favourable alleles were 76.5, 56.9 and 69.6%, respectively. Among the 102 wheat varieties, 30 contained all the three favourable genes, 45 contained two of the three favourable genes and 27 contained only one. There are eight wheat varieties (7.8%) in hybrid state at the TaCWI-A1 locus. Third, the designed FM linked to water-saving gene Dreb-B1 were validated on 102 wheat varieties. The results showed that the haplotypes of 47 wheat varieties at the Dreb-B1 locus were same as that of Opata 85, and 55 wheat varieties showed the signal expected for W7984 (Opata 85 and W7984 are parents of the ITMI mapping population). This information will be useful for the wheat breeding

  9. Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

    Directory of Open Access Journals (Sweden)

    Steinmetz André

    2010-09-01

    Full Text Available Abstract Background Plants of the Huperziaceae family, which comprise the two genera Huperzia and Phlegmariurus, produce various types of lycopodium alkaloids that are used to treat a number of human ailments, such as contusions, swellings and strains. Huperzine A, which belongs to the lycodine type of lycopodium alkaloids, has been used as an anti-Alzheimer's disease drug candidate. Despite their medical importance, little genomic or transcriptomic data are available for the members of this family. We used massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform to generate a substantial EST dataset for Huperzia serrata (H. serrata and Phlegmariurus carinatus (P. carinatus as representative members of the Huperzia and Phlegmariurus genera, respectively. H. serrata and P. carinatus are important plants for research on the biosynthesis of lycopodium alkaloids. We focused on gene discovery in the areas of bioactive compound biosynthesis and transcriptional regulation as well as genetic marker detection in these species. Results For H. serrata, 36,763 unique putative transcripts were generated from 140,930 reads totaling over 57,028,559 base pairs; for P. carinatus, 31,812 unique putative transcripts were generated from 79,920 reads totaling over 30,498,684 base pairs. Using BLASTX searches of public databases, 16,274 (44.3% unique putative transcripts from H. serrata and 14,070 (44.2% from P. carinatus were assigned to at least one protein. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG orthology annotations revealed that the functions of the unique putative transcripts from these two species cover a similarly broad set of molecular functions, biological processes and biochemical pathways. In particular, a total of 20 H. serrata candidate cytochrome P450 genes, which are more abundant in leaves than in roots and might be involved in lycopodium alkaloid biosynthesis, were found based on the comparison of H

  10. A Putative Nononcogene Addiction Gene Target and Marker for Radiosensitivity in High-Risk Prostate Cancer

    Science.gov (United States)

    2014-12-01

    prostate cancer cell lines (LNCaP and CRW22-RVI) with increasing concentrations of several selected RNASEH2A inhibitors (0.5–20 μM) at 37°C for 4h or 24...further increase of drug concentration had no or little additional effect on cell viability suggesting that RNASEH2 inhibition in cells is achieved...sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication

  11. Faecal phytic acid and its relation to other putative markers of risk for colorectal cancer.

    OpenAIRE

    Owen, R W; Weisgerber, U M; Spiegelhalder, B; Bartsch, H

    1996-01-01

    AIMS--Phytic acid, a major constituent of cereals, pulses, and seeds has been advocated as an important antioxidant component of dietary fibre that affords possible protection against colorectal cancer. This is supported by experimental studies showing it has antineoplastic activity in animal models of both colon and breast cancer. To date the concentration of faecal phytic acid in human clinical groups has not been evaluated. Therefore the faecal phytic acid content of adenoma patients drawn...

  12. Mapping the flow of information within the putative mirror neuron system during gesture observation

    NARCIS (Netherlands)

    Schippers, Marleen B.; Keysers, Christian

    2011-01-01

    The putative mirror neuron system may either function as a strict feed-forward system or as a dynamic control system. A strict feed-forward system would predict that action observation leads to a predominantly temporal -> parietal -> premotor flow of information in which a visual representation is t

  13. Genic non-coding microsatellites in the rice genome: characterization, marker design and use in assessing genetic and evolutionary relationships among domesticated groups

    Directory of Open Access Journals (Sweden)

    Singh Nagendra

    2009-03-01

    Full Text Available Abstract Background Completely sequenced plant genomes provide scope for designing a large number of microsatellite markers, which are useful in various aspects of crop breeding and genetic analysis. With the objective of developing genic but non-coding microsatellite (GNMS markers for the rice (Oryza sativa L. genome, we characterized the frequency and relative distribution of microsatellite repeat-motifs in 18,935 predicted protein coding genes including 14,308 putative promoter sequences. Results We identified 19,555 perfect GNMS repeats with densities ranging from 306.7/Mb in chromosome 1 to 450/Mb in chromosome 12 with an average of 357.5 GNMS per Mb. The average microsatellite density was maximum in the 5' untranslated regions (UTRs followed by those in introns, promoters, 3'UTRs and minimum in the coding sequences (CDS. Primers were designed for 17,966 (92% GNMS repeats, including 4,288 (94% hypervariable class I types, which were bin-mapped on the rice genome. The GNMS markers were most polymorphic in the intronic region (73.3% followed by markers in the promoter region (53.3% and least in the CDS (26.6%. The robust polymerase chain reaction (PCR amplification efficiency and high polymorphic potential of GNMS markers over genic coding and random genomic microsatellite markers suggest their immediate use in efficient genotyping applications in rice. A set of these markers could assess genetic diversity and establish phylogenetic relationships among domesticated rice cultivar groups. We also demonstrated the usefulness of orthologous and paralogous conserved non-coding microsatellite (CNMS markers, identified in the putative rice promoter sequences, for comparative physical mapping and understanding of evolutionary and gene regulatory complexities among rice and other members of the grass family. The divergence between long-grained aromatics and subspecies japonica was estimated to be more recent (0.004 Mya compared to short

  14. Sequencing, De Novo Assembly, and Annotation of the Transcriptome of the Endangered Freshwater Pearl Bivalve, Cristaria plicata, Provides Novel Insights into Functional Genes and Marker Discovery.

    Directory of Open Access Journals (Sweden)

    Bharat Bhusan Patnaik

    Full Text Available The freshwater mussel Cristaria plicata (Bivalvia: Eulamellibranchia: Unionidae, is an economically important species in molluscan aquaculture due to its use in pearl farming. The species have been listed as endangered in South Korea due to the loss of natural habitats caused by anthropogenic activities. The decreasing population and a lack of genomic information on the species is concerning for environmentalists and conservationists. In this study, we conducted a de novo transcriptome sequencing and annotation analysis of C. plicata using Illumina HiSeq 2500 next-generation sequencing (NGS technology, the Trinity assembler, and bioinformatics databases to prepare a sustainable resource for the identification of candidate genes involved in immunity, defense, and reproduction.The C. plicata transcriptome analysis included a total of 286,152,584 raw reads and 281,322,837 clean reads. The de novo assembly identified a total of 453,931 contigs and 374,794 non-redundant unigenes with average lengths of 731.2 and 737.1 bp, respectively. Furthermore, 100% coverage of C. plicata mitochondrial genes within two unigenes supported the quality of the assembler. In total, 84,274 unigenes showed homology to entries in at least one database, and 23,246 unigenes were allocated to one or more Gene Ontology (GO terms. The most prominent GO biological process, cellular component, and molecular function categories (level 2 were cellular process, membrane, and binding, respectively. A total of 4,776 unigenes were mapped to 123 biological pathways in the KEGG database. Based on the GO terms and KEGG annotation, the unigenes were suggested to be involved in immunity, stress responses, sex-determination, and reproduction. A total of 17,251 cDNA simple sequence repeats (cSSRs were identified from 61,141 unigenes (size of >1 kb with the most abundant being dinucleotide repeats.This dataset represents the first transcriptome analysis of the endangered mollusc, C. plicata

  15. Dietary proteins improve endothelial function under fasting conditions but not in the postprandial state, with no effects on markers of low-grade inflammation

    NARCIS (Netherlands)

    Teunissen-Beekman, Karianna F. M.; Dopheide, Janneke; Geleijnse, Johanna M.; Bakker, Stephan J. L.; Brink, Elizabeth J.; de Leeuw, Peter W.; Schalkwijk, Casper G.; van Baak, Marleen A.

    2015-01-01

    Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first

  16. Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies

    NARCIS (Netherlands)

    S. Lie Fong (Sharon); P.J. Lugtenburg (Pieternella); I. Schipper; A.P.N. Themmen (Axel); F.H. de Jong (Frank); P. Sonneveld (Pieter); J.S.E. Laven (Joop)

    2008-01-01

    textabstractBACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Müllerian hormone (AMH) constitutes a sensitive marker of ovarian

  17. Exceptional error minimization in putative primordial genetic codes

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2009-11-01

    Full Text Available Abstract Background The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces. Results We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level. Conclusion The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high

  18. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    Science.gov (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  19. Evaluation of cleaved amplified polymorphic sequence markers for Chamaecyparis obtusa based on expressed sequence tag information from Cryptomeria japonica.

    Science.gov (United States)

    Matsumoto, A; Tsumura, Y

    2004-12-01

    We have developed and evaluated sequence-tagged site (STS) primers based on expressed sequence-tag information derived from sugi (Cryptomeria japonica) for use in hinoki (Chamaecyparis obtusa), a species that belongs to a different family (although it appears to be fairly closely related to sugi). Of the 417 C. japonica STS primer pairs we screened, 120 (approximately 30%) were transferable and provided specific PCR amplification products from 16 C. obtusa plus trees. We used haploid megagametophytes to investigate the homology of 80 STS fragments between C. obtusa and C. japonica and to identify orthologous loci. Nearly 90% of the fragments showed high (>70%) degrees of similarity between the species, and 35 STSs indicated homology to entries with the same putative function in a public DNA database. Of the 120 STS fragments amplified, 72 showed restriction fragment length polymorphisms; in addition, the CC2430 primers detected amplicon length polymorphism. We assessed the inheritance pattern of 27 cleaved amplified polymorphic sequence markers, using 20 individuals from the segregation population. All the markers analyzed were consistent with the marker inheritance patterns obtained from the screening panel, and no markers (except CC2716) showed significant (Pobtusa. Most of the markers should also provide reliable anchor loci for comparative mapping studies of the C. obtusa and C. japonica genomes.

  20. Molecular mapping of the putative gonadoblastoma locus on the Y chromosome.

    Science.gov (United States)

    Salo, P; Kääriäinen, H; Petrovic, V; Peltomäki, P; Page, D C; de la Chapelle, A

    1995-11-01

    Based on the high incidence of gonadoblastoma in females with XY gonadal dysgenesis or 45,X/46,XY mosaicism, the existence of a susceptibility locus on the Y chromosome (GBY) has been postulated. We attempted to map GBY by making use of a recently developed dense map of Y-chromosomal sequence-tagged sites (STSs). In two female patients with gonadoblastoma, small marker chromosomes contained portions of the Y chromosome, and a single region of overlap could be defined extending from probe pDP97 in interval 4B, which contains the centromere, to marker sY182 in interval 5E of the proximal long arm. This interval is contained in a YAC contig that comprises approximately 4 Mb of DNA. Our findings confirm the previous localization of GBY and greatly refine it. The localization of GBY overlaps with the region to which a putative growth determinant, GCY, was recently assigned.

  1. Spatial patterns of diversity at the putative recognition domain of resistance gene candidates in wild bean populations.

    Science.gov (United States)

    de Meaux, J; Neema, C

    2003-01-01

    Leucine Rich Repeats (LRR) domains have been identified on most known plant resistance genes and appear to be involved in the specific recognition of pathogen strains. Here we explore the processes which may drive the evolution of this putative recognition domain. We developed AFLP markers specifically situated in the LRR domain of members of the PRLJ1 complex Resistance Gene Candidate (RGC) family identified in common bean (Phaseolus vulgaris). Diversity for these markers was assessed in ten wild populations of P. vulgaris and compared to locally co-occurring pathogen populations of Colletotrichum lindemuthianum. Nine PRLJ1 LRR specific markers were obtained. Marker sequences revealed that RGC diversity at PRLJ1 is similar to that at other complex R-loci. Wild bean populations showed contrasting levels of PRLJ1 LRR diversity and were all significantly differentiated. We could not detect an effect of local C. lindemuthianum population diversity on the spatial distribution of P. vulgaris PRLJ1 diversity. However, host populations have been previously assessed for neutral (RAPD) markers and for resistance phenotypes to six strains of C. lindemuthianum isolated from cultivated bean fields. A comparative analysis of PRLJ1 LRR diversity and host diversity for resistance phenotypes indicated that evolutionary processes related to the antagonistic C. lindemuthianum/P. vulgaris interaction are likely to have shaped molecular diversity of the putative recognition domains of the PRLJ1 RGC family members.

  2. Putative regulatory factors associated with intramuscular fat content.

    Directory of Open Access Journals (Sweden)

    Aline S M Cesar

    Full Text Available Intramuscular fat (IMF content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG, biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA and co-expression network methods, such as partial correlation coefficient with information theory (PCIT, regulatory impact factor (RIF and phenotypic impact factor (PIF were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H and low (L GEBV and 77 DEG (FDR 10% were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1, MPC1 and UBL5 (RIF2 and a host of small RNAs, including miR-1281 (PIF. These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.

  3. Mismatch negativity (MMN) and sensory auditory processing in children aged 9-12 years presenting with putative antecedents of schizophrenia.

    Science.gov (United States)

    Bruggemann, Jason M; Stockill, Helen V; Lenroot, Rhoshel K; Laurens, Kristin R

    2013-09-01

    Identification of markers of abnormal brain function in children at-risk of schizophrenia may inform early intervention and prevention programs. Individuals with schizophrenia are characterised by attenuation of MMN amplitude, which indexes automatic auditory sensory processing. The current aim was to examine whether children who may be at increased risk of schizophrenia due to their presenting multiple putative antecedents of schizophrenia (ASz) are similarly characterised by MMN amplitude reductions, relative to typically developing (TD) children. EEG was recorded from 22 ASz and 24 TD children aged 9 to 12 years (matched on age, sex, and IQ) during a passive auditory oddball task (15% duration deviant). ASz children were those presenting: (1) speech and/or motor development lags/problems; (2) social, emotional, or behavioural problems in the clinical range; and (3) psychotic-like experiences. TD children presented no antecedents, and had no family history of a schizophrenia spectrum disorder. MMN amplitude, but not latency, was significantly greater at frontal sites in the ASz group than in the TD group. Although the MMN exhibited by the children at risk of schizophrenia was unlike that of their typically developing peers, it also differed from the reduced MMN amplitude observed in adults with schizophrenia. This may reflect developmental and disease effects in a pre-prodromal phase of psychosis onset. Longitudinal follow-up is necessary to establish the developmental trajectory of MMN in at-risk children.

  4. Characterization of variable EST SSR markers for Norway spruce (Picea abies L.

    Directory of Open Access Journals (Sweden)

    Spiess Nadine

    2011-10-01

    Full Text Available Abstract Background Norway spruce is widely distributed across Europe and the predominant tree of the Alpine region. Fast growth and the fact that timber can be harvested cost-effectively in relatively young populations define its status as one of the economically most important tree species of Northern Europe. In this study, EST derived simple sequence repeat (SSR markers were developed for the assessment of putative functional diversity in Austrian Norway spruce stands. Results SSR sequences were identified by analyzing 14,022 publicly available EST sequences. Tri-nucleotide repeat motifs were most abundant in the data set followed by penta- and hexa-nucleotide repeats. Specific primer pairs were designed for sixty loci. Among these, 27 displayed polymorphism in a testing population of 16 P. abies individuals sampled across Austria and in an additional screening population of 96 P. abies individuals from two geographically distinct Austrian populations. Allele numbers per locus ranged from two to 17 with observed heterozygosity ranging from 0.075 to 0.99. Conclusions We have characterized variable EST SSR markers for Norway spruce detected in expressed genes. Due to their moderate to high degree of variability in the two tested screening populations, these newly developed SSR markers are well suited for the analysis of stress related functional variation present in Norway spruce populations.

  5. Evaluation of oxidative stress markers for the early diagnosis of allograft rejection in feline renal allotransplant recipients with normal renal function

    OpenAIRE

    Halling, Krista B.; Ellison, Gary W.; Armstrong, Don; Aoyagi, Kasumi; Detrisac, Carol J.; Graham, John P.; Newell, Susan P.; Martin, Frank G.; Van Gilder, James M.

    2004-01-01

    The purpose of this study was to identify oxidative damage to renal allografts during graft rejection by evaluating changes in oxidative markers and plasma lactate levels in feline renal allotransplant recipients. Heterotopic renal allotransplantations were performed between 8 adult feline cross-matched donors. Following 14 d of immunosuppression, the drugs were discontinued to allow allograft rejection. Baseline and serial postoperative evaluations of serum creatinine, plasma lactate, plasma...

  6. De novo assembly, gene annotation, and marker discovery in stored-product pest Liposcelis entomophila (Enderlein using transcriptome sequences.

    Directory of Open Access Journals (Sweden)

    Dan-Dan Wei

    Full Text Available BACKGROUND: As a major stored-product pest insect, Liposcelis entomophila has developed high levels of resistance to various insecticides in grain storage systems. However, the molecular mechanisms underlying resistance and environmental stress have not been characterized. To date, there is a lack of genomic information for this species. Therefore, studies aimed at profiling the L. entomophila transcriptome would provide a better understanding of the biological functions at the molecular levels. METHODOLOGY/PRINCIPAL FINDINGS: We applied Illumina sequencing technology to sequence the transcriptome of L. entomophila. A total of 54,406,328 clean reads were obtained and that de novo assembled into 54,220 unigenes, with an average length of 571 bp. Through a similarity search, 33,404 (61.61% unigenes were matched to known proteins in the NCBI non-redundant (Nr protein database. These unigenes were further functionally annotated with gene ontology (GO, cluster of orthologous groups of proteins (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG databases. A large number of genes potentially involved in insecticide resistance were manually curated, including 68 putative cytochrome P450 genes, 37 putative glutathione S-transferase (GST genes, 19 putative carboxyl/cholinesterase (CCE genes, and other 126 transcripts to contain target site sequences or encoding detoxification genes representing eight types of resistance enzymes. Furthermore, to gain insight into the molecular basis of the L. entomophila toward thermal stresses, 25 heat shock protein (Hsp genes were identified. In addition, 1,100 SSRs and 57,757 SNPs were detected and 231 pairs of SSR primes were designed for investigating the genetic diversity in future. CONCLUSIONS/SIGNIFICANCE: We developed a comprehensive transcriptomic database for L. entomophila. These sequences and putative molecular markers would further promote our understanding of the molecular mechanisms underlying

  7. CLONING, SEQUENCE ANALYSIS, AND CHARACTERIZATION OF PUTATIVE BETA-LACTAMASE OF STENOTROPHOMONAS MALTOPHILIA

    Directory of Open Access Journals (Sweden)

    Chong Seng Shueh

    2012-10-01

    Full Text Available The main objective of current study was to explore the function of chromosomal putative beta-lactamase gene (smlt 0115 in clinical Stenotrophomonas maltophilia. Antibiotic susceptibility test (AST screening for current antimicrobial drugs was done and Minimum Inhibitory Concentration (MIC level towards beta-lactams was determined by E-test. Putative beta-lactamase gene of S. maltophilia was amplified via PCR, with specific primers, then cloned into pET-15 expression plasmid and transformed into Escherichia coli BL21. The gene was sequenced and analyzed. The expressed protein was purified by affinity chromatography and the kinetic assay was performed. S. maltophilia ATCC 13637 was included in this experiment. Besides, a hospital strain which exhibited resistant to a series of beta-lactams including cefepime was identified via AST and MIC, hence it was named as S2 strain and was considered in this study. Sequencing result showed that putative beta-lactamase gene obtained from ATCC 13637 and S2 strains were predicted to have cephalosporinase activity by National Center for Biotechnology Information (NCBI blast program. Differences in the sequences of both ATCC 13637 and S2 strains were found via ClustalW alignment software. Kinetic assay proved a cephalosporinase characteristic produced by E. coli BL21 clone that overexpressed the putative beta-lactamase gene cloned under the control of an external promoter. Yet, expressed protein purified from S2 strain had high catalytic activity against beta-lactam antibiotics which was 14-fold higher than expressed protein purified from ATCC 13637 strain. This study represents the characterization analysis of putative beta-lactamase gene (smlt 0115 of S. maltophilia. The presence of the respective gene in the chromosome of S. maltophilia suggested that putative beta-lactamase gene (smlt 0115 of S. maltophilia plays a role in beta-lactamase resistance.

  8. Literature Review of Discourse Marker

    Institute of Scientific and Technical Information of China (English)

    赵蕴萱; 王孝伟

    2011-01-01

    This paper is devoted to supplying theoretical foundation for discourse markers(DMs),introducing the relevant definitions as well as the previous classifications of DMs.The functions of discourse markers are also added so as to provide a deep insight into

  9. Further insight into reproductive incompatibility between putative cryptic species of the Bemisia tabaci whitefly complex.

    Science.gov (United States)

    Qin, Li; Pan, Li-Long; Liu, Shu-Sheng

    2016-04-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), with its global distribution and extensive genetic diversity, is now known to be a complex of over 35 cryptic species. However, a satisfactory resolution of the systematics of this species complex is yet to be achieved. Here, we designed experiments to examine reproductive compatibility among species with different levels of mitochondrial cytochrome oxidase I (mtCOI) divergence. The data show that putative species with mtCOI divergence of >8% between them consistently exhibited complete reproductive isolation. However, two of the putative species, Asia II 9 and Asia II 3, with mtCOI divergence of 4.47% between them, exhibited near complete reproductive compatibility in one direction of their cross, and partial reproductive compatibility in the other direction. Together with some recent reports on this topic from the literature, our data indicates that, while divergence in the mtCOI sequences provides a valid molecular marker for species delimitation in most clades, more genetic markers and more sophisticated molecular phylogeny will be required to achieve adequate delimitation of all species in this whitefly complex. While many attempts have been made to examine the reproductive compatibility among genetic groups of the B. tabaci complex, our study represents the first effort to conduct crossing experiments with putative species that were chosen with considerations of their genetic divergence. In light of the new data, we discuss the best strategy and protocols to conduct further molecular phylogenetic analysis and crossing trials, in order to reveal the overall pattern of reproductive incompatibility among species of this whitefly complex.

  10. Putative impact of RNA editing on drug discovery.

    Science.gov (United States)

    Decher, Niels; Netter, Michael F; Streit, Anne K

    2013-01-01

    Virtually all organisms use RNA editing as a powerful post-transcriptional mechanism to recode genomic information and to increase functional protein diversity. The enzymatic editing of pre-mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability. However, RNA editing is also an important mechanism for genes expressed outside the brain. The fact that RNA editing breaks the 'one gene encodes one protein' hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the 'wrong' protein. This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets. These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology. Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high-throughput screens, rational drug design or choosing the right model organism for target validation.

  11. 大学英语教师课堂话语标记语元语用功能分析%Analysis on Meta-pragmatic Functions of College English Teachers’ Discourse Markers in Classrooms

    Institute of Scientific and Technical Information of China (English)

    朱金兰; 孙安妮

    2016-01-01

    在Verschueren 提出的元语用意识及Halliday的系统功能语法三大元功能基础上,分析大学英语教师课堂话语标记语与其元语用意识之间关系,分析教师元语用意识是如何指导和调控其对话语标记语作出选择的,并具体讨论课堂语境下教师话语标记语人际互动、信息传递及语篇衔接三种元语用功能。研究结果将为英语教师课堂话语语用研究提供一个新视角。%Based on Verschueren ’ s meta-pragmatic awareness and Halliday ’ s three metafunctions , the article studies the relationship between English teachers ’ discourse markers and their meta-pragmatic aware-ness in college classrooms , analyzing how the teachers are monitored and guided by their meta-pragmatic awareness when using language .The results also indicate the meta-pragmatic functions of college English teachers ’ discourse markers , such as interpersonal function , information transmission function and textual co-hesion function .The results will provide a new perspective for the further study of English teachers ’ classroom discourse .

  12. Ceramic subsurface marker prototypes

    Energy Technology Data Exchange (ETDEWEB)

    Lukens, C.E. [Rockwell International Corp., Richland, WA (United States). Rockwell Hanford Operations

    1985-05-02

    The client submitted 5 sets of porcelain and stoneware subsurface (radioactive site) marker prototypes (31 markers each set). The following were determined: compressive strength, thermal shock resistance, thermal crazing resistance, alkali resistance, color retention, and chemical resistance.

  13. Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Rohit B. [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States); Wang, Qingde [Department of Surgery, University of Pittsburgh, PA 15261 (United States); Khillan, Jaspal S., E-mail: khillan@pitt.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States)

    2013-07-12

    Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

  14. The reproducibility of different metabolic markers for muscle fiber type distributions investigated by functional {sup 31}P-MRS during dynamic exercise

    Energy Technology Data Exchange (ETDEWEB)

    Rzanny, Reinhard; Hiepe, Patrick; Gussew, Alexander; Reichenbach, Juergen R. [Univ. Hospital Jena (Germany). Medical Physics Group, Inst. of Diagnostics and Interventional Radiology; Stutzig, Norman [Univ. of Stuttgart (Germany). Exercise Science, Inst. of Sport and Movement Science; Thorhauer, Hans-Alexander [Friedrich-Schiller-Univ. Jena (Germany). Exercise Science, Inst. of Sports Science

    2016-07-01

    The objective of the study was to investigate the reproducibility of exercise induced pH-heterogeneity by splitting of the inorganic phosphate (Pi) signal in the corresponding {sup 31}P-MRS spectra and to compare results of this approach with other fiber-type related markers, like phosphocreatine/adenosine triphosphate (PCr/ATP) ratio, and PCr-recovery parameters. Subjects (N = 3) with different sportive background were tested in 10 test sessions separated by at least 3 days. A MR-compatible pedal ergometer was used to perform the exercise and to induce a pH-based splitting of the Pi-signal in {sup 31}P-MR spectra of the medial gastrocnemius muscle. The PCr recovery was analyzed using a non-negative least square algorithm (NNLS) and multi-exponential regression analysis to estimate the number of non-exponential components as well as their amplitude and time constant. The reproducibility of the estimated metabolic marker and the resulting fiber-type distributions between the 10 test sessions were compared. The reproducibility (standard deviation between measurements) based on (1) Pi components varied from 2% to 4%, (2) PCr recovery time components varied from 10% to 12% and (3) phosphate concentrations at rest varied from 8% to 11% between test sessions. Due to the sportive activity differences between the 3 subjects were expected in view of fiber type distribution. All estimated markers indicate the highest type I percentage for volunteer 3 medium for volunteer 2 and the lowest for volunteer 1. The relative high reproducibility of pH dependent Pi components during exercise indicates a high potential of this method to estimate muscle fiber-type distributions in vivo. To make this method usable not only to detect differences in muscle fiber distributions but also to determine individual fiber-type volume contents it is therefore recommended to validate this marker by histological methods and to reveal the effects of muscle fiber recruitments and fiber-type specific

  15. Identification of putative candidate genes for juvenile wood density in Pinus radiata.

    Science.gov (United States)

    Li, Xinguo; Wu, Harry X; Southerton, Simon G

    2012-08-01

    Wood formation is a complex developmental process driven by the annual activity of the vascular cambium. Conifers usually produce juvenile wood at young ages followed by mature wood for the rest of their lifetime. Juvenile wood exhibits poorer wood quality (i.e., lower density) compared with mature wood and can account for up to 50% of short-rotation harvested logs, thus representing a major challenge for commercial forestry globally. Wood density is an important quality trait for many timber-related products. Understanding the molecular mechanisms involved in the regulation of juvenile wood density is critical for the improvement of juvenile wood quality via marker-aided selection. A previous study has identified several candidate genes affecting mature wood density in Picea sitchensis (Bong.) Carr.; however, genes associated with juvenile wood density in conifers remain poorly characterized. Here, cDNA microarrays containing 3320 xylem unigenes were used to investigate genes differentially transcribed in juvenile wood with high (HD) and low density (LD) in Pinus radiata D.Don. In total, 814 xylem unigenes with differential transcription were identified in at least one of two microarray experiments and 73 genes (45 for HD, 28 for LD) were identified in both experiments, thus representing putative candidate genes for juvenile wood density. Interestingly, cellulose synthases (PrCesA3, PrCesA11) and sucrose synthase (SuSy), which are involved in secondary cell wall formation, had stronger transcription in juvenile wood with HD, while genes functioning in primary wall formation (pectin synthesis, cell expansion and other modifications) were more transcribed in LD wood. Cell wall genes encoding monolignol biosynthesis enzymes, arabinogalactan proteins, actins and tubulins were differentially transcribed in either HD or LD juvenile wood; however, the latter had exclusively greater transcription of genes involved in monolignol polymerization (laccase and peroxidase). The

  16. Bilingual Discourse Markers in Indigenous Languages

    Science.gov (United States)

    Torres, Lourdes

    2006-01-01

    This review of research considers the occurrence and function of Spanish discourse markers and other particles in indigenous speech. I discuss important research that has examined these phenomena and refer to studies of bilingual discourse markers in other non-indigenous language contact situations to address unresolved issues concerning the form…

  17. Analysis of community composition of sulfur-oxidizing bacteria in hypersaline and soda lakes using soxB as a functional molecular marker.

    Science.gov (United States)

    Tourova, Tatjana P; Slobodova, Natalija V; Bumazhkin, Boris K; Kolganova, Tatjana V; Muyzer, Gerard; Sorokin, Dimitry Y

    2013-05-01

    The diversity of soxB gene encoding a key enzyme of the Sox pathway sulfate thiohydrolase has been investigated in pure cultures of various halophilic and haloalkaliphilic sulfur-oxidizing bacteria (SOB) and in salt and soda lakes in southwestern Siberia and Egypt. The gene was detected in the majority of strains belonging to eleven SOB genera excluding members of genera Thiohalospira and Thioalkalimicrobium. The uncultured diversity of soxB in salt and soda lakes was low with a majority of detected sequences belonging to autotrophic SOB from the Gammaproteobacteria. In addition, the soxB analysis allowed detection of putative heterotrophic Gamma- and Alphaproteobacterial SOB yet unknown in culture. All clone libraries obtained from soda lakes contained soxB belonging to the genus Thioalkalivibrio in agreement with the cultivation results. Besides, representatives of the genera Halothiobacillus, Marinobacter, and Halochromatium and of the family Rhodobacteraceae have been detected in both type of saline lakes. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  18. Expressed sequence tags (ESTs and simple sequence repeat (SSR markers from octoploid strawberry (Fragaria × ananassa

    Directory of Open Access Journals (Sweden)

    Bies Dawn H

    2005-06-01

    Full Text Available Abstract Background Cultivated strawberry (Fragaria × ananassa represents one of the most valued fruit crops in the United States. Despite its economic importance, the octoploid genome presents a formidable barrier to efficient study of genome structure and molecular mechanisms that underlie agriculturally-relevant traits. Many potentially fruitful research avenues, especially large-scale gene expression surveys and development of molecular genetic markers have been limited by a lack of sequence information in public databases. As a first step to remedy this discrepancy a cDNA library has been developed from salicylate-treated, whole-plant tissues and over 1800 expressed sequence tags (EST's have been sequenced and analyzed. Results A putative unigene set of 1304 sequences – 133 contigs and 1171 singlets – has been developed, and the transcripts have been functionally annotated. Homology searches indicate that 89.5% of sequences share significant similarity to known/putative proteins or Rosaceae ESTs. The ESTs have been functionally characterized and genes relevant to specific physiological processes of economic importance have been identified. A set of tools useful for SSR development and mapping is presented. Conclusion Sequences derived from this effort may be used to speed gene discovery efforts in Fragaria and the Rosaceae in general and also open avenues of comparative mapping. This report represents a first step in expanding molecular-genetic analyses in strawberry and demonstrates how computational tools can be used to optimally mine a large body of useful information from a relatively small data set.

  19. Transcriptome survey of Patagonian southern beech Nothofagus nervosa (= N. Alpina: assembly, annotation and molecular marker discovery

    Directory of Open Access Journals (Sweden)

    Torales Susana L

    2012-07-01

    Full Text Available Abstract Background Nothofagus nervosa is one of the most emblematic native tree species of Patagonian temperate forests. Here, the shotgun RNA-sequencing (RNA-Seq of the transcriptome of N. nervosa, including de novo assembly, functional annotation, and in silico discovery of potential molecular markers to support population and associations genetic studies, are described. Results Pyrosequencing of a young leaf cDNA library generated a total of 111,814 high quality reads, with an average length of 447 bp. De novo assembly using Newbler resulted into 3,005 tentative isotigs (including alternative transcripts. The non-assembled sequences (singletons were clustered with CD-HIT-454 to identify natural and artificial duplicates from pyrosequencing reads, leading to 21,881 unique singletons. 15,497 out of 24,886 non-redundant sequences or unigenes, were successfully annotated against a plant protein database. A substantial number of simple sequence repeat markers (SSRs were discovered in the assembled and annotated sequences. More than 40% of the SSR sequences were inside ORF sequences. To confirm the validity of these predicted markers, a subset of 73 SSRs selected through functional annotation evidences were successfully amplified from six seedlings DNA samples, being 14 polymorphic. Conclusions This paper is the first report that shows a highly precise representation of the mRNAs diversity present in young leaves of a native South American tree, N. nervosa, as well as its in silico deduced putative functionality. The reported Nothofagus transcriptome sequences represent a unique resource for genetic studies and provide a tool to discover genes of interest and genetic markers that will greatly aid questions involving evolution, ecology, and conservation using genetic and genomic approaches in the genus.

  20. Transcriptome survey of Patagonian southern beech Nothofagus nervosa (= N. Alpina): assembly, annotation and molecular marker discovery.

    Science.gov (United States)

    Torales, Susana L; Rivarola, Máximo; Pomponio, María F; Fernández, Paula; Acuña, Cintia V; Marchelli, Paula; Gonzalez, Sergio; Azpilicueta, María M; Hopp, Horacio Esteban; Gallo, Leonardo A; Paniego, Norma B; Poltri, Susana N Marcucci

    2012-07-02

    Nothofagus nervosa is one of the most emblematic native tree species of Patagonian temperate forests. Here, the shotgun RNA-sequencing (RNA-Seq) of the transcriptome of N. nervosa, including de novo assembly, functional annotation, and in silico discovery of potential molecular markers to support population and associations genetic studies, are described. Pyrosequencing of a young leaf cDNA library generated a total of 111,814 high quality reads, with an average length of 447 bp. De novo assembly using Newbler resulted into 3,005 tentative isotigs (including alternative transcripts). The non-assembled sequences (singletons) were clustered with CD-HIT-454 to identify natural and artificial duplicates from pyrosequencing reads, leading to 21,881 unique singletons. 15,497 out of 24,886 non-redundant sequences or unigenes, were successfully annotated against a plant protein database. A substantial number of simple sequence repeat markers (SSRs) were discovered in the assembled and annotated sequences. More than 40% of the SSR sequences were inside ORF sequences. To confirm the validity of these predicted markers, a subset of 73 SSRs selected through functional annotation evidences were successfully amplified from six seedlings DNA samples, being 14 polymorphic. This paper is the first report that shows a highly precise representation of the mRNAs diversity present in young leaves of a native South American tree, N. nervosa, as well as its in silico deduced putative functionality. The reported Nothofagus transcriptome sequences represent a unique resource for genetic studies and provide a tool to discover genes of interest and genetic markers that will greatly aid questions involving evolution, ecology, and conservation using genetic and genomic approaches in the genus.

  1. A Study on College English Teachers' Use of discourse Markers

    Institute of Scientific and Technical Information of China (English)

    王冬梅

    2009-01-01

    The paper intends to explore the use of Discourse Markers (DMs) by college English teachers in the classroom and to achieve an understanding of the range of functions that those discourse markers perform.

  2. Gestational Diabetes Mellitus Worsens the Profile of Cardiometabolic Risk Markers and Decrease Indexes of Beta-Cell Function Independently of Insulin Resistance in Nondiabetic Women with a Parental History of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alina Sokup

    2014-01-01

    Full Text Available Background. Women with a history of both parental type 2 diabetes (pt2DM and previous gestational diabetes (pGDM represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women. Methods. Anthropometric parameters, glucose regulation (OGTT, insulin resistance (HOMA-IR, beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2–24 months postpartum, and 35 controls. Results. Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, P=0.04. The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR. Conclusions. pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR.

  3. Gestational diabetes mellitus worsens the profile of cardiometabolic risk markers and decrease indexes of beta-cell function independently of insulin resistance in nondiabetic women with a parental history of type 2 diabetes.

    Science.gov (United States)

    Sokup, Alina; Ruszkowska-Ciastek, Barbara; Walentowicz-Sadłecka, Małgorzata; Grabiec, Marek; Rość, Danuta

    2014-01-01

    Women with a history of both parental type 2 diabetes (pt2DM) and previous gestational diabetes (pGDM) represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA-IR), beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2-24 months postpartum, and 35 controls. Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, P = 0.04). The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR. pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR.

  4. A rapid approach to evaluate putative nursery sites for penaeid prawns

    Science.gov (United States)

    Taylor, Matthew D.; Smith, James A.; Boys, Craig A.; Whitney, Hannah

    2016-08-01

    Identifying nursery habitats for an aquatic species generally requires tracing adult individuals back through time and space to the area or habitat in which they developed as juveniles. We develop and trial a study design and analytical approach to evaluate the suitability of using stable isotopes to trace emigrating prawns to putative nursery sites, and evaluate assumptions inherent in the application of the approach using two penaeid species with Type-II life cycles: Penaeus (Melicertus) plebejus and Metapenaeus macleayi. Prawns were collected in putative nursery sites within the Hunter River, Australia, and analysed as composite samples of 6 individuals to provide habitat-specific isotopic signatures. Prawns emigrating from the mouth of the river were used as a proxy for individuals recruiting to the adult population, and assigned to putative nursery sites using a probabilistic mixing model and a simple, distance-based approach. Bivariate (δ15N and δ13C) isotopic data was sufficient to distinguish prawns from different putative nursery sites, and isotopic composition correlated closely with salinity. Approximately 90% of emigrating prawns collected could be assigned to these sites using bivariate isotopic data, and both analytical approaches gave similar results. The design developed here is broadly applicable to a suite of penaeid species, but its application will be most powerful when sampling is also aimed at understanding nursery function by simultaneous monitoring of size structure/growth, density, and trophic relationships within nursery habitats.

  5. Marker Recycling in Candida albicans through CRISPR-Cas9-Induced Marker Excision

    Science.gov (United States)

    2017-01-01

    ABSTRACT We describe here a new approach to marker recycling, a controlled sequence of steps in which a genetic marker is selected and then lost. Marker recycling is important for genetic manipulation, because it allows a single selection marker to be used repeatedly. Our approach relies upon the ability of the CRISPR-Cas9 system to make a targeted double-strand break in DNA and the expectation that a double-strand break within a selection marker may promote recombination between directly repeated sequences that flank the marker. We call the approach CRISPR-Cas9-induced marker excision (CRIME). We tested the utility of this approach with the fungal pathogen Candida albicans, which is typically diploid. We used two selection markers, modified to include flanking direct repeats. In a proof-of-principle study, we created successive homozygous deletions in three genes through use of the two markers and had one of the markers available in the final strain for further selection and recycling. This strategy will accelerate the creation of multiple-mutant strains in C. albicans. CRISPR-Cas9 systems have been applied to many organisms, so the genetic design principles described here may be broadly applicable. IMPORTANCE It is critical to be able to alter genes in order to elucidate their functions. These alterations often rely upon markers that allow selection for a rare cell in a population that has incorporated a piece of DNA. The number of alterations that can be accomplished is thus limited by the number of selection markers that are available. This limitation is circumvented by marker recycling strategies, in which a marker is eliminated after its initial use. Then, the marker can be used again. In this report, we describe a new marker recycling strategy that is enabled by recently developed CRISPR-Cas9 technology. PMID:28317025

  6. Bone turnover markers and parameters of functional and structural state in patients with chronic spinal cord injuries in 5 years and later after the trauma

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    M.A. Bystrytska

    2017-08-01

    Full Text Available Background. The increased life expectancy of persons with complete spinal cord injury brings into focus the late complications of spinal cord injuries (SCI including osteoporosis. Purpose of the study was to evaluate the bone mineral status and bone turnover markers in patients with chronic spinal cord injury of 5 years and over. Materials and methods. Seventy-three subjects who suffered from complete spinal cord injury with tetra- or paraplegia and 57 healthy persons were examined. Bone status was determined by ultrasound (US densitometry of the calcaneal bone using quantitative ultrasonometer Sahara (Hologic Inc., model 04874, 2008. Bone turnover markers in the peripheral blood (osteocalcin, procollagen type 1 propeptide (P1NP, collagen type 1 cross-linked C-telopeptide (β-CTx and vitamin D were defined by electrochemiluminescence method. Results. SCI patients demonstrated significantly lower parameters of bone mineral status compared with the subjects of the control group. The stiffness index (SI was 51.4 ± 11.8 % vs. 98.5 ± 16.6 % (p < 0.05 in men and 50.1 ± 9.8 % vs. 92 9 ± 11.1 % (p < 0.05 in women. There was significant reduction of bone mass index in SCI patients and in the individuals of the control group after 2 years, but bone loss over time was significantly worse in SCI patients (–16.5 ± 2.4 % vs. –2.5 ± 0.9 %, respectively; p < 0.05. In SCI patients levels of bone turnover markers were significantly higher than the relative values in Ukrainian population. Conclusions. SCI with complete spinal cord injury leads to increased bone resorption with formation of secondary osteoporosis (according to the data of ultrasound densitometry of the calcaneal bone. In the late posttraumatic period bone destruction processes are slowing down but remain higher than in the population as a whole, combined with low levels of vitamin D and absence of axial load results in continued loss of trabecular bone mass.

  7. Phytophthora infestans specific phosphorylation patterns and new putative control targets.

    Science.gov (United States)

    Frades, Itziar; Andreasson, Erik

    2016-04-01

    In this study we applied biomathematical searches of gene regulatory mechanisms to learn more about oomycete biology and to identify new putative targets for pesticides or biological control against Phytophthora infestans. First, oomycete phylum-specific phosphorylation motifs were found by discriminative n-gram analysis. We found 11.600 P. infestans specific n-grams, mapping 642 phosphoproteins. The most abundant group among these related to phosphatidylinositol metabolism. Due to the large number of possible targets found and our hypothesis that multi-level control is a sign of usefulness as targets for intervention, we identified overlapping targets with a second screen. This was performed to identify proteins dually regulated by small RNA and phosphorylation. We found 164 proteins to be regulated by both sRNA and phosphorylation and the dominating functions where phosphatidylinositol signalling/metabolism, endocytosis, and autophagy. Furthermore we performed a similar regulatory study and discriminative n-gram analysis of proteins with no clear orthologs in other species and proteins that are known to be unique to P. infestans such as the RxLR effectors, Crinkler (CRN) proteins and elicitins. We identified CRN proteins with specific phospho-motifs present in all life stages. PITG_12626, PITG_14042 and PITG_23175 are CRN proteins that have species-specific phosphorylation motifs and are subject to dual regulation.

  8. Small intestinal mucosa expression of putative chaperone fls485

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    Raupach Kerstin

    2010-03-01

    Full Text Available Abstract Background Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. Methods fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. Results fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. Conclusions Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.

  9. Small intestinal mucosa expression of putative chaperone fls485.

    Science.gov (United States)

    Reinartz, Andrea; Ehling, Josef; Franz, Susanne; Simon, Verena; Bravo, Ignacio G; Tessmer, Claudia; Zentgraf, Hanswalter; Lyer, Stefan; Schneider, Ursula; Köster, Jan; Raupach, Kerstin; Kämmerer, Elke; Klaus, Christina; Tischendorf, Jens J W; Kopitz, Jürgen; Alonso, Angel; Gassler, Nikolaus

    2010-03-07

    Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.

  10. Expression and characterization of rice putative PAUSED gene

    Institute of Scientific and Technical Information of China (English)

    Chengguo Yao; Liangfa Ge; Wei Li; Botao Zhao; Chaoqun Li; Kangcheng Ruan; Hongxuan Lin; Youxin Jin

    2008-01-01

    In Arab idopsis, PA USED ( PSD ) encodes the ortholog of loslp/ exportin-t, which mediates the nuclear export of transfer RNA (tRNA) in yeast and mammals. However, in monocot plants such as rice, knowledge of the corresponding ortholog is limited, and its effects on growth development and productivity remain unknown. In this study, we verified a rice transfer-DNA insertional mutantpsd line and analyzed its phenotypes;the mutant displayed severe morphological defects including retarded development and low fertility compared with wild-type rice. Examining intronless tRNA-Tyr and intron-containing pre-tRNA-Ala expression levels in cytoplasmic and nuclear fraction with Northern blot analysis between wild -type and mutant leaf tissue suggested that rice PSD might be involved in tRNA export from the nucleus to the cytoplasm.Additionally, reverse transcription-polymerase chain reaction analysis revealed that PSD transcript was expressed throughout normal rice plant development, and subcellular localization assays showed that rice PSD protein was present in both the nucleus and cytoplasm. In summary, our data implied that the putative PSD gene might be indispensable for normal rice development and its function might be the same as that ofArabidopsis PSD.

  11. Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Weikop, Pia; Olsen, Niels Vidiendal

    2016-01-01

    measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial). Results: EPO had no cumulative...... and change in verbal memory. Conclusions: Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory...... pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders....

  12. Putative Corneal Neuralgia Responding to Vitamin D Supplementation

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    Eric L. Singman

    2013-09-01

    Full Text Available A patient with putative corneal neuralgia was incidentally discovered to have hypovitaminosis D. Supplementation of vitamin D appears to have led to a resolution of the patient's pain, whereas other efforts to treat the patient were unsuccessful.

  13. The resistive index is a marker of renal function, pathology, prognosis, and responsiveness to steroid therapy in chronic kidney disease patients.

    Science.gov (United States)

    Hanamura, Kikuno; Tojo, Akihiro; Kinugasa, Satoshi; Asaba, Kensuke; Fujita, Toshiro

    2012-01-01

    To evaluate the significance of the renal resistive index (RI) as a noninvasive marker of renal histological damage and a prognostic indicator, we examined RI by Doppler ultrasonography in 202 chronic kidney disease (CKD) patients who underwent renal biopsy. RI increased as the CKD stage progressed and correlated with age, systolic blood pressure, estimated glomerular filtration rate (eGFR), and renal histological changes, including glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Prognostic evaluation with a median follow-up period of 38.5 months revealed that patients with RI ≥ 0.7 (high RI group, n = 39) had significantly poorer renal survival than those with RI histological damage, and renal prognosis, and a possible determinant of indication for steroids.

  14. Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial.

    Science.gov (United States)

    Richter, Chesney K; Skulas-Ray, Ann C; Fleming, Jennifer A; Link, Christina J; Mukherjea, Ratna; Krul, Elaine S; Kris-Etherton, Penny M

    2017-05-01

    Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (-2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

  15. Putative Enzymes of UV Photoproduct Repair

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    Cynthia J. Sakofsky

    2011-01-01

    Full Text Available In order to determine the biological relevance of two S. acidocaldarius proteins to the repair of UV photoproducts, the corresponding genes (Saci_1227 and Saci_1096 were disrupted, and the phenotypes of the resulting mutants were examined by various genetic assays. The disruption used integration by homologous recombination of a functional but heterologous pyrE gene, promoted by short sequences attached to both ends via PCR. The phenotypic analyses of the disruptants confirmed that ORF Saci_1227 encodes a DNA photolyase which functions in vivo, but they could not implicate ORF Saci_1096 in repair of UV- or other externally induced DNA damage despite its similarity to genes encoding UV damage endonucleases. The success of the gene-disruption strategy, which used 5′ extensions of PCR primers to target cassette integration, suggests potential advantages for routine construction of Sulfolobus strains.

  16. De novo assembly of the Indo-Pacific humpback dolphin leucocyte transcriptome to identify putative genes involved in the aquatic adaptation and immune response.

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    Duan Gui

    Full Text Available BACKGROUND: The Indo-Pacific humpback dolphin (Sousa chinensis, a marine mammal species inhabited in the waters of Southeast Asia, South Africa and Australia, has attracted much attention because of the dramatic decline in population size in the past decades, which raises the concern of extinction. So far, this species is poorly characterized at molecular level due to little sequence information available in public databases. Recent advances in large-scale RNA sequencing provide an efficient approach to generate abundant sequences for functional genomic analyses in the species with un-sequenced genomes. PRINCIPAL FINDINGS: We performed a de novo assembly of the Indo-Pacific humpback dolphin leucocyte transcriptome by Illumina sequencing. 108,751 high quality sequences from 47,840,388 paired-end reads were generated, and 48,868 and 46,587 unigenes were functionally annotated by BLAST search against the NCBI non-redundant and Swiss-Prot protein databases (E-value<10(-5, respectively. In total, 16,467 unigenes were clustered into 25 functional categories by searching against the COG database, and BLAST2GO search assigned 37,976 unigenes to 61 GO terms. In addition, 36,345 unigenes were grouped into 258 KEGG pathways. We also identified 9,906 simple sequence repeats and 3,681 putative single nucleotide polymorphisms as potential molecular markers in our assembled sequences. A large number of unigenes were predicted to be involved in immune response, and many genes were predicted to be relevant to adaptive evolution and cetacean-specific traits. CONCLUSION: This study represented the first transcriptome analysis of the Indo-Pacific humpback dolphin, an endangered species. The de novo transcriptome analysis of the unique transcripts will provide valuable sequence information for discovery of new genes, characterization of gene expression, investigation of various pathways and adaptive evolution, as well as identification of genetic markers.

  17. A putatively novel form of spontaneous coordination in neural activity.

    Science.gov (United States)

    Hermer-Vazquez, Raymond; Hermer-Vazquez, Linda; Srinivasan, Sridhar

    2009-04-06

    We simultaneously recorded local field potentials from three sites along the olfactory-entorhinal axis in rats lightly anesthetized with isoflurane, as part of another experiment. While analyzing the initial data from that experiment with spectrograms, we discovered a potentially novel form of correlated neural activity, with near-simultaneous occurrence across the three widely separated brain sites. After validating their existence further, we named these events Synchronous Frequency Bursts (SFBs). Here we report our initial investigations into their properties and their potential functional significance. In Experiment 1, we found that SFBs have highly regular properties, consisting of brief (approximately 250 ms), high amplitude bursts of LFP energy spanning frequency ranges from the delta band (1-4 Hz) to at least the low gamma band (30-50 Hz). SFBs occurred almost simultaneously across recording sites, usually with onsets sites. While the SFBs had fairly typical, exponentially decaying power spectral density plots, their coherence structure was unusual, with high peaks in several narrow frequency ranges and little coherence in other bands. In Experiment 2, we found that SFBs occurred far more often under light anesthesia than deeper anesthetic states, and were especially prevalent as the animals regained consciousness. Finally, in Experiment 3 we showed that SFBs occur simultaneously at a significant rate across brain sites from putatively different functional subsystems--olfactory versus motor pathways. We suggest that SFBs do not carry information per se, but rather, play a role in coordinating activity in different frequency bands, potentially brain-wide, as animals progress from sleep or anesthesia toward full consciousness.

  18. Tissue factor residues that putatively interact with membrane phospholipids.

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    Ke Ke

    Full Text Available Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit, bound to the integral membrane protein, tissue factor (the regulatory subunit. Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue factor/factor VIIa complex relative to its membrane-bound protein substrates, factors IX and X. In this study, we individually mutated to alanine all the putative phosphatidylserine-interactive residues in the tissue factor ectodomain and measured their effects on tissue factor cofactor function (activation of factors IX and X by tissue factor/factor VIIa, and clotting of plasma. Some tissue factor mutants exhibited decreased activity in all three assays, with the most profound defects observed from mutations in or near the flexible loop from Lys159 to Gly164. The decreased activity of all of these tissue factor mutants could be partially or completely overcome by increasing the phosphatidylserine content of tissue factor-liposomes. Additionally, yeast surface display was used to screen a random library of tissue factor mutants for enhanced factor VIIa binding. Surprisingly, mutations at a single amino acid (Lys165 predominated, with the Lys165→Glu mutant exhibiting a 3-fold enhancement in factor VIIa binding affinity. Our studies reveal the functional contributions of residues in the C-terminal half of the tissue factor ectodomain that are implicated in interacting with phosphatidylserine headgroups to enhance tissue factor cofactor activity, possibly by allosterically modulating the conformation of the adjacent substrate-binding exosite region of tissue factor.

  19. Identification, characterization and utilization of unigene derived microsatellite markers in tea (Camellia sinensis L.

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    Mohapatra Trilochan

    2009-05-01

    Full Text Available Abstract Background Despite great advances in genomic technology observed in several crop species, the availability of molecular tools such as microsatellite markers has been limited in tea (Camellia sinensis L.. The development of microsatellite markers will have a major impact on genetic analysis, gene mapping and marker assisted breeding. Unigene derived microsatellite (UGMS markers identified from publicly available sequence database have the advantage of assaying variation in the expressed component of the genome with unique identity and position. Therefore, they can serve as efficient and cost effective alternative markers in such species. Results Considering the multiple advantages of UGMS markers, 1,223 unigenes were predicted from 2,181 expressed sequence tags (ESTs of tea (Camellia sinensis L.. A total of 109 (8.9% unigenes containing 120 SSRs were identified. SSR abundance was one in every 3.55 kb of EST sequences. The microsatellites mainly comprised of di (50.8%, tri (30.8%, tetra (6.6%, penta (7.5% and few hexa (4.1% nucleotide repeats. Among the dinucleotide repeats, (GAn.(TCn were most abundant (83.6%. Ninety six primer pairs could be designed form 83.5% of SSR containing unigenes. Of these, 61 (63.5% primer pairs were experimentally validated and used to investigate the genetic diversity among the 34 accessions of different Camellia spp. Fifty one primer pairs (83.6% were successfully cross transferred to the related species at various levels. Functional annotation of the unigenes containing SSRs was done through gene ontology (GO characterization. Thirty six (60% of them revealed significant sequence similarity with the known/putative proteins of Arabidopsis thaliana. Polymorphism information content (PIC ranged from 0.018 to 0.972 with a mean value of 0.497. The average heterozygosity expected (HE and observed (Ho obtained was 0.654 and 0.413 respectively, thereby suggesting highly heterogeneous nature of tea. Further, test

  20. Molecular marker databases.

    Science.gov (United States)

    Lai, Kaitao; Lorenc, Michał Tadeusz; Edwards, David

    2015-01-01

    The detection and analysis of genetic variation plays an important role in plant breeding and this role is increasing with the continued development of genome sequencing technologies. Molecular genetic markers are important tools to characterize genetic variation and assist with genomic breeding. Processing and storing the growing abundance of molecular marker data being produced requires the development of specific bioinformatics tools and advanced databases. Molecular marker databases range from species specific through to organism wide and often host a variety of additional related genetic, genomic, or phenotypic information. In this chapter, we will present some of the features of plant molecular genetic marker databases, highlight the various types of marker resources, and predict the potential future direction of crop marker databases.

  1. Putative adverse outcome pathways relevant to neurotoxicity

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  2. Mesoderm patterning and morphogenesis in the polychaete Alitta virens (Spiralia, Annelida): Expression of mesodermal markers Twist, Mox, Evx and functional role for MAP kinase signaling.

    Science.gov (United States)

    Kozin, Vitaly V; Filimonova, Daria A; Kupriashova, Ekaterina E; Kostyuchenko, Roman P

    2016-05-01

    Mesoderm represents the evolutionary youngest germ layer and forms numerous novel tissues in bilaterian animals. Despite the established conservation of the gene regulatory networks that drive mesoderm differentiation (e.g. myogenesis), mechanisms of mesoderm specification are highly variable in distant model species. Thus, broader phylogenetic sampling is required to reveal common features of mesoderm formation across bilaterians. Here we focus on a representative of Spiralia, the marine annelid Alitta virens, whose mesoderm development is still poorly investigated on the molecular level. We characterize three novel early mesodermal markers for A. virens - Twist, Mox, and Evx - which are differentially expressed within the mesodermal lineages. The Twist mRNA is ubiquitously distributed in the fertilized egg and exhibits specific expression in endomesodermal- and ectomesodermal-founder cells at gastrulation. Twist is expressed around the blastopore and later in a segmental metameric pattern. We consider this expression to be ancestral, and in support of the enterocoelic hypothesis of mesoderm evolution. We also revealed an early pattern of the MAPK activation in A. virens that is different from the previously reported pattern in spiralians. Inhibition of the MAPK pathway by U0126 disrupts the metameric Twist and Mox expression, indicating an early requirement of the MAPK cascade for proper morphogenesis of endomesodermal tissues.

  3. Transcriptome Profile of the Asian Giant Hornet (Vespa mandarinia) Using Illumina HiSeq 4000 Sequencing: De Novo Assembly, Functional Annotation, and Discovery of SSR Markers.

    Science.gov (United States)

    Patnaik, Bharat Bhusan; Park, So Young; Kang, Se Won; Hwang, Hee-Ju; Wang, Tae Hun; Park, Eun Bi; Chung, Jong Min; Song, Dae Kwon; Kim, Changmu; Kim, Soonok; Lee, Jae Bong; Jeong, Heon Cheon; Park, Hong Seog; Han, Yeon Soo; Lee, Yong Seok

    2016-01-01

    Vespa mandarinia found in the forests of East Asia, including Korea, occupies the highest rank in the arthropod food web within its geographical range. It serves as a source of nutrition in the form of Vespa amino acid mixture and is listed as a threatened species, although no conservation measures have been implemented. Here, we performed de novo assembly of the V. mandarinia transcriptome by Illumina HiSeq 4000 sequencing. Over 60 million raw reads and 59,184,811 clean reads were obtained. After assembly, a total of 66,837 unigenes were clustered, 40,887, 44,455, and 22,390 of which showed homologous matches against the PANM, Unigene, and KOG databases, respectively. A total of 15,675 unigenes were assigned to Gene Ontology terms, and 5,132 unigenes were mapped to 115 KEGG pathways. The zinc finger domain (C2H2-like), serine/threonine/dual specificity protein kinase domain, and RNA recognition motif domain were among the top InterProScan domains predicted for V. mandarinia sequences. Among the unigenes, we identified 534,922 cDNA simple sequence repeats as potential markers. This is the first transcriptomic analysis of the wasp V. mandarinia using Illumina HiSeq 4000. The obtained datasets should promote the search for new genes to understand the physiological attributes of this wasp.

  4. Transcriptome Profile of the Asian Giant Hornet (Vespa mandarinia Using Illumina HiSeq 4000 Sequencing: De Novo Assembly, Functional Annotation, and Discovery of SSR Markers

    Directory of Open Access Journals (Sweden)

    Bharat Bhusan Patnaik

    2016-01-01

    Full Text Available Vespa mandarinia found in the forests of East Asia, including Korea, occupies the highest rank in the arthropod food web within its geographical range. It serves as a source of nutrition in the form of Vespa amino acid mixture and is listed as a threatened species, although no conservation measures have been implemented. Here, we performed de novo assembly of the V. mandarinia transcriptome by Illumina HiSeq 4000 sequencing. Over 60 million raw reads and 59,184,811 clean reads were obtained. After assembly, a total of 66,837 unigenes were clustered, 40,887, 44,455, and 22,390 of which showed homologous matches against the PANM, Unigene, and KOG databases, respectively. A total of 15,675 unigenes were assigned to Gene Ontology terms, and 5,132 unigenes were mapped to 115 KEGG pathways. The zinc finger domain (C2H2-like, serine/threonine/dual specificity protein kinase domain, and RNA recognition motif domain were among the top InterProScan domains predicted for V. mandarinia sequences. Among the unigenes, we identified 534,922 cDNA simple sequence repeats as potential markers. This is the first transcriptomic analysis of the wasp V. mandarinia using Illumina HiSeq 4000. The obtained datasets should promote the search for new genes to understand the physiological attributes of this wasp.

  5. Global Transcriptome Sequencing Identifies Chlamydospore Specific Markers in Candida albicans and Candida dubliniensis

    LENUS (Irish Health Repository)

    Palige, Katja

    2013-04-15

    Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.

  6. Is androstadienone a putative human pheromone?

    Science.gov (United States)

    Marazziti, D; Torri, P; Baroni, S; Catena Dell'Osso, M; Consoli, G; Boncinelli, V

    2011-01-01

    On the basis of different evidences, androstadienone, a steroid compound produced in the armpit, has been proposed as a human pheromone, although its physiological levels appear too low to induce a response under experimental conditions. For this reason, the majority of researchers in this area puts into question the "legitimacy" of androstadienone, and prefers to consider the axillary extracts in its entirety, like a sort of "medicinal tea", the components of which still remain to be identified, but that taken together may induce a response, or function as a carrier of other active substances. Another option is that androstadienone acts with varying degrees of potency and, at lower concentrations, according to the context and to specific behavioral situations. The aim of this paper is to review all relevant data regarding androstadienone, in order to ascertain whether it may be considered a physiological pheromone and, as such, a possible target of future modulators of some human behaviors.

  7. The impact of decreases in air temperature and increases in ozone on markers of endothelial function in individuals having type-2 diabetes

    Science.gov (United States)

    Several studies have reported an association between air pollution and endothelial dysfunction, especially in individuals having diabetes. However, very few studies have examined the impact of air temperature on endothelial function. The objective of this analysis was to investig...

  8. Large-Scale Fusion of Gray Matter and Resting-State Functional MRI Reveals Common and Distinct Biological Markers across the Psychosis Spectrum in the B-SNIP Cohort.

    Science.gov (United States)

    Wang, Zheng; Meda, Shashwath A; Keshavan, Matcheri S; Tamminga, Carol A; Sweeney, John A; Clementz, Brett A; Schretlen, David J; Calhoun, Vince D; Lui, Su; Pearlson, Godfrey D

    2015-01-01

    To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses [schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar I disorder with psychosis (BP)] and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives, and 242 healthy controls (1). All subjects underwent structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) scanning. Joint-independent component analysis (jICA) was used to fuse sMRI gray matter and rs-fMRI amplitude of low-frequency fluctuations data to identify the relationship between the two modalities. jICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal-striatal-thalamic-cerebellar network and structural abnormalities in the default mode network was found to be common across psychotic diagnoses and correlated with cognitive function, social function, and schizo-bipolar scale scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality). Using a multivariate-fused approach involving two widely used imaging markers, we demonstrate both shared and distinct biological traits across the psychosis spectrum. Furthermore, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes.

  9. What is the clinical value of cancer stem cell markers in gliomas?

    DEFF Research Database (Denmark)

    Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær; Hansen, Steinbjørn

    2013-01-01

    Recent data indicate that cancer stem cells (CSCs) are responsible for resistance of glioblastomas to radiotherapy and chemotherapy, thereby contributing to the poor survival of these patients. In order to identify novel prognostic markers in gliomas, several CSC markers have been investigated....... This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament markers...... (nestin), RNA-binding proteins (Musashi-1) and transcription factors (BMI1, SOX2, Id1 and Oct-4) qualified for this review. The level of CD133 and nestin increased with increasing malignancy grade, and for both markers a prognostic significance was identified in the majority of the studies. Moreover...

  10. Cloning and molecular characterization of a putative voltage-gated sodium channel gene in the crayfish.

    Science.gov (United States)

    Coskun, Cagil; Purali, Nuhan

    2016-06-01

    Voltage-gated sodium channel genes and associated proteins have been cloned and studied in many mammalian and invertebrate species. However, there is no data available about the sodium channel gene(s) in the crayfish, although the animal has frequently been used as a model to investigate various aspects of neural cellular and circuit function. In the present work, by using RNA extracts from crayfish abdominal ganglia samples, the complete open reading frame of a putative sodium channel gene has firstly been cloned and molecular properties of the associated peptide have been analyzed. The open reading frame of the gene has a length of 5793 bp that encodes for the synthesis of a peptide, with 1930 amino acids, that is 82% similar to the α-peptide of a sodium channel in a neighboring species, Cancer borealis. The transmembrane topology analysis of the crayfish peptide indicated a pattern of four folding domains with several transmembrane segments, as observed in other known voltage-gated sodium channels. Upon analysis of the obtained sequence, functional regions of the putative sodium channel responsible for the selectivity filter, inactivation gate, voltage sensor, and phosphorylation have been predicted. The expression level of the putative sodium channel gene, as defined by a qPCR method, was measured and found to be the highest in nervous tissue.

  11. Ribulose-1,5-bisphosphate carboxylase/oxygenase genes as a functional marker for chemolithoautotrophic halophilic sulfur-oxidizing bacteria in hypersaline habitats.

    Science.gov (United States)

    Tourova, Tatjana P; Kovaleva, Olga L; Sorokin, Dimitry Yu; Muyzer, Gerard

    2010-07-01

    The presence and diversity of the cbb genes encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) (a key enzyme of the Calvin-Benson cycle of autotrophic CO(2) assimilation) were investigated in pure cultures of seven genera of halophilic chemolithoautotrophic sulfur-oxidizing bacteria (SOB) and in sediments from a hypersaline lake in which such bacteria have been recently discovered. All of the halophilic SOB strains (with the exception of Thiohalomonas nitratireducens) possessed the cbbL gene encoding RuBisCO form I, while the cbbM gene encoding RuBisCO form II was detected only in some of the pure cultures. The general topologies of the CbbL/CbbM trees and the 16S rRNA gene tree were different, but both markers showed that the halophilic SOB genera formed independent lineages in the Gammaproteobacteria. In some cases, such as with several strains of the genus Thiohalospira and with Thioalkalibacter halophilus, the cbbL clustering was incongruent with the positions of these strains on the ribosomal tree. In the cbbM tree, the clustering of Thiohalospira and Thiohalorhabdus strains was incongruent with their branching in both cbbL and 16S rRNA gene trees. cbbL and cbbM genes related to those found in the analysed halophilic SOB were also detected in a sediment from a hypersaline lake in Kulunda Steppe (Russia). Most of the cbbL and cbbM genes belonged to members of the genus Thiohalorhabdus. In the cbbL clone library, sequences related to those of Halothiobacillus and Thiohalospira were detected as minor components. Some of the environmental cbbM sequences belonged to as yet unknown phylotypes, representing deep lineages of halophilic autotrophs.

  12. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

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    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  13. The solution structure of ChaB, a putative membrane ion antiporter regulator from Escherichia coli

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    Iannuzzi Pietro

    2004-08-01

    Full Text Available Abstract Background ChaB is a putative regulator of ChaA, a Na+/H+ antiporter that also has Ca+/H+ activity in E. coli. ChaB contains a conserved 60-residue region of unknown function found in other bacteria, archaeabacteria and a series of baculoviral proteins. As part of a structural genomics project, the structure of ChaB was elucidated by NMR spectroscopy. Results The structure of ChaB is composed of 3 α-helices and a small sheet that pack tightly to form a fold that is found in the cyclin-box family of proteins. Conclusion ChaB is distinguished from its putative DNA binding sequence homologues by a highly charged flexible loop region that has weak affinity to Mg2+ and Ca2+ divalent metal ions.

  14. Salivary PYY: a putative bypass to satiety.

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    Andres Acosta

    Full Text Available Peptide YY(3-36 is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY(3-36 is also present in murine as well as in human saliva. In mice, salivary PYY(3-36 derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY(3-36 induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO mice, a sustained increase in PYY(3-36 was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY(3-36 resulted in a significant long-term reduction in food intake (FI and body weight (BW. Thus this study provides evidence for new functions of the previously characterized gut peptide PYY(3-36 suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity.

  15. A putative viral defence mechanism in archaeal cells

    Directory of Open Access Journals (Sweden)

    Reidun Lillestøl

    2006-01-01

    Full Text Available Clusters of regularly spaced direct repeats, separated by unconserved spacer sequences, are ubiquitous in archaeal chromosomes and occur in some plasmids. Some clusters constitute around 1% of chromosomal DNA. Similarly structured clusters, generally smaller, also occur in some bacterial chromosomes. Although early studies implicated these clusters in segregation/partition functions, recent evidence suggests that the spacer sequences derive from extrachromosomal elements, and, primarily, viruses. This has led to the proposal that the clusters provide a defence against viral propagation in cells, and that both the mode of inhibition of viral propagation and the mechanism of adding spacer-repeat units to clusters, are dependent on RNAs transcribed from the clusters. Moreover, the putative inhibitory apparatus (piRNA-based may be evolutionarily related to the interference RNA systems (siRNA and miRNA, which are common in eukarya. Here, we analyze all the current data on archaeal repeat clusters and provide some new insights into their diverse structures, transcriptional properties and mode of structural development. The results are consistent with larger cluster transcripts being processed at the centers of the repeat sequences and being further trimmed by exonucleases to yield a dominant, intracellular RNA species, which corresponds approximately to the size of a spacer. Furthermore, analysis of the extensive clusters of Sulfolobus solfataricus strains P1 and P2B provides support for the presence of a flanking sequence adjoining a cluster being a prerequisite for the incorporation of new spacer-repeat units, which occurs between the flanking sequence and the cluster. An archaeal database summarizing the data will be maintained at http://dac.molbio.ku.dk/dbs/SRSR/.

  16. Impact of oxidative stress on early postoperative knee function and muscle injury biochemical markers: Is it possible to create an ischemic preconditioning effect in sequential ischemic surgical procedures?

    Science.gov (United States)

    Aktaş, Erdem; Atay, Çiğdem; Deveci, Mehmet Ali; Arıkan, Murat; Toğral, Güray; Yıldırım, Ahmet

    2015-01-01

    Simultaneous bilateral total knee arthroplasty (TKA) with prolonged tourniquet time has the potential to trigger ischemia-reperfusion injury, which can adversely affect knee function. Studies suggest that the magnitude of injury is less if it occurs following an ischemic event which takes place in another part of the body, known as ischemic preconditioning (IPC). The purpose of this study was to investigate the impact of oxidative stress on muscle injury and knee function and to elucidate if potential IPC effect can attenuate ischemia-reperfusion injury metabolites and prevent poor functional outcomes in single-stage bilateral TKA. Thirty patients who underwent single-stage bilateral TKA under tourniquet were enrolled in the study. All procedures were initiated from the right limb. Upon completion of the procedure, the left tourniquet was inflated 20 minutes after the first tourniquet was deflated. The tourniquet time was noted. Pre- and postoperative levels of malondialdehyde (MDH), creatine kinase (CK), and lactate dehydrogenase (LDH) were evaluated. Knee function was assessed postoperatively at 1 month using WOMAC score. Postoperative levels of MDH, CK, and LDH were significantly increased in both extremities compared to preoperative levels. Serum MDH, CK, and LDH levels were not found to be correlated with tourniquet time for either extremity. Compared to the left extremity, the right extremity revealed increased postoperative oxidative stress, which was indicated by elevated serum MDH, CK, and LDH levels. Although tourniquet time and postoperative serum MDH, CK, and LDH levels were not found to be correlated with WOMAC index in either knee, the average change in WOMAC score at 1 month postoperatively was found to be higher in the left knee compared to the right. The biochemical and functional outcomes can be attributed to potential IPC effect. During bilateral TKA, a 20-minute interval between tourniquets can create IPC effect and attenuate the magnitude of

  17. Markers of low-grade inflammation and endothelial dysfunction are related to reduced information processing speed and executive functioning in an older population - the Hoorn Study.

    Science.gov (United States)

    Heringa, S M; van den Berg, E; Reijmer, Y D; Nijpels, G; Stehouwer, C D A; Schalkwijk, C G; Teerlink, T; Scheffer, P G; van den Hurk, K; Kappelle, L J; Dekker, J M; Biessels, G J

    2014-02-01

    Low-grade inflammation and endothelial dysfunction are related to cognitive decline and dementia, in a complex interplay with vascular factors and aging. We investigated, in an older population, low-grade inflammation and endothelial dysfunction in relation to detailed assessment of cognitive functioning. Furthermore, we explored this association within the context of vascular factors. 377 participants (73 ± 6 years) of the population-based Hoorn Study were included. In plasma samples of 2000-2001 (n=363) and/or 2005-2008 (n=323), biomarkers were determined of low-grade inflammation (CRP, TNF-alpha, IL-6, IL-8, SAA, MPO, and sICAM-1) and endothelial dysfunction (vWF, sICAM-1, sVCAM-1, sTM, sE-selectin). In 2005-2008, all participants underwent neuropsychological examination. Composite z-scores were computed for low-grade inflammation and endothelial dysfunction at both time points, and for six domains of cognitive functioning (abstract reasoning, memory, information processing speed, attention and executive functioning, visuoconstruction, and language). The association between low-grade inflammation and endothelial dysfunction, and cognitive functioning was evaluated with linear regression analysis. In secondary analyses, we explored the relation with vascular risk factors and cardiovascular disease. Low-grade inflammation and endothelial dysfunction were associated with worse performance on information processing speed and attention and executive functioning, in prospective and cross-sectional analyses (standardized betas ranging from -0.20 to -0.10). No significant relation with other cognitive domains was observed. Adjusting for vascular factors slightly attenuated the associations. Low-grade inflammation and endothelial dysfunction accounted for only 2.6% explained variance in cognitive functioning, on top of related vascular risk factors and cardiovascular disease. Bootstrapping analyses show that low-grade inflammation and endothelial dysfunction mediate the

  18. Neurobiological markers of exercise-related brain plasticity in older adults.

    Science.gov (United States)

    Voss, Michelle W; Erickson, Kirk I; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; Phillips, Siobhan M; Wójcicki, Thomas R; Mailey, Emily L; Olson, Erin A; Gothe, Neha; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Cook, Marc D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2013-02-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

  19. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  20. Serotonin, neural markers, and memory.

    Science.gov (United States)

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence.

  1. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

    Science.gov (United States)

    Buss, Sebastian J; Emami, Mostafa; Mereles, Derliz; Korosoglou, Grigorios; Kristen, Arnt V; Voss, Andreas; Schellberg, Dieter; Zugck, Christian; Galuschky, Christian; Giannitsis, Evangelos; Hegenbart, Ute; Ho, Anthony D; Katus, Hugo A; Schonland, Stefan O; Hardt, Stefan E

    2012-09-18

    The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p chains (p value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers. In the largest serial investigation reported so far, reduced LV longitudinal function served as an independent predictor of survival in AL amyloidosis and offered incremental information beyond standard clinical

  2. Dichotomous Distribution of Putative Cholinergic Interneurons in Mouse Accessory Olfactory Bulb

    Science.gov (United States)

    Marking, Sarah; Krosnowski, Kurt; Ogura, Tatsuya; Lin, Weihong

    2017-01-01

    Sensory information processing in the olfactory bulb (OB) relies on diverse populations of bulbar interneurons. In rodents, the accessory OB (AOB) is divided into two bulbar regions, the anterior (aAOB) and posterior (pAOB), which differ substantially in their circuitry connections and associated behaviors. We previously identified and characterized a large number of morphologically diverse cholinergic interneurons in the main OB (MOB) using transgenic mice to visualize the cell bodies of choline acetyltransferase (ChAT-expressing neurons and immunolabeling (Krosnowski et al., 2012)). However, whether there are cholinergic neurons in the AOB is controversial and there is no detailed characterization of such neurons. Using the same line of ChAT(bacterial artificial chromosome, BAC)-enhanced green fluorescent protein (eGFP) transgenic mice, we investigated cholinergic neurons in the AOB. We found significant differences in the number and location of GFP-expressing (GFP+), putative cholinergic interneurons between the aAOB and pAOB. The highest numbers of GFP+ interneurons were found in the aAOB glomerular layer (aGL) and pAOB mitral/tufted cell layer (pMCL). We also noted a high density of GFP+ interneurons encircling the border region of the pMCL. Interestingly, a small subset of glomeruli in the middle of the GL receives strong MCL GFP+ nerve processes. These local putative cholinergic-innervated glomeruli are situated just outside the aGL, setting the boundary between the pGL and aGL. Many but not all GFP+ neurons in the AOB were weakly labeled with antibodies against ChAT and vesicular acetylcholine transporter (VAChT). We further determined if these GFP+ interneurons differ from other previously characterized interneuron populations in the AOB and found that AOB GFP+ interneurons express neither GABAergic nor dopaminergic markers and most also do not express the glutamatergic marker. Similar to the cholinergic interneurons of the MOB, some AOB GFP+ interneurons

  3. Determinação de cistatina C como marcador de função renal Cystatin C measurement as renal function marker

    Directory of Open Access Journals (Sweden)

    Letícia Aparecida Lopes Neri

    2010-12-01

    Full Text Available INTRODUÇÃO: A cistatina C sérica tem sido apontada como um marcador de filtração glomerular. OBJETIVO: Realizar a validação de um método específico e automatizado, a imunonefelometria, mensurando os níveis séricos de cistatina C por meio do nefelômetro da empresa Behring (BN II e correlacionar resultados obtidos entre pacientes transplantados. O ensaio perfaz o intervalo de referência de 0,23-7,25 mg/l. A imprecisão intra e interensaio foi de 8,73% e 5,38%, respectivamente. A recuperação analítica da cistatina C após adição de controle foi entre 86,7 % e 98% (média 92,3%. A estabilidade da cistatina C à temperatura ambiente, sob refrigeração e sob congelamento foi testada. A perda mais significativa foi encontrada nas amostras armazenadas à temperatura ambiente, em que foram perdidos até 10% da concentração inicial. Foi encontrado coeficiente de variação de 14,79% para sensibilidade analítica. Durante todo o processo foram comparados os resultados com o controle de qualidade e obtivemos bons resultados. Depois desses testes, nós comparamos as correlações em três grupos de pacientes transplantados renais sob diferentes esquemas de imunossupressão (n = 197 - azatioprina (n = 36, micofenolato mofetil (n = 131 e sirolimus (n = 30 - entre as equações de estimativa de filtração glomerular (Cockroft Gault, Nankivell e Modification of Diet in Renal Disease e cistatina C sérica ou creatinina sérica. CONCLUSÃO: O ensaio nefelométrico cistatina C pode perfeitamente ser adequado à nossa rotina laboratorial e as correlações entre creatinina sérica e as diferentes equações de estimativa de filtração glomerular são melhores do que quando comparamos as mesmas à cistatina C nos três grupos, independentemente da terapia imunossupressora utilizada.INTRODUCTION: Serum cystatin C has been identified as a glomerular filtration marker. OBJECTIVE: To validate immunonephelometry, a specific and automated method, by

  4. Marker development in ornamental plants

    NARCIS (Netherlands)

    Heusden, van A.W.; Arens, P.

    2009-01-01

    Development of markers for a new crop or development of additional markers for a crop where markers have been developed in the past raises the question of the intended use of the markers. Depending on the different objectives in mind one marker type may be better suited then another. In general one

  5. The Use and Functions of Discourse Markers in EFL Classroom Interaction Los usos y las funciones de los marcadores del discurso en la interacción en el aula de inglés como lengua extranjera

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Chapetón Castro

    2009-04-01

    Full Text Available The aim of this paper is to investigate classroom interaction in the context of English as a foreign language being the teacher a nonnative speaker of the language. One specific aspect of classroom interaction and language use is the focus of attention, namely discourse markers (DMs. Using data from an EFL class, this study describes the occurrences and frequencies of DMs. It also provides an account for the main functions of DMs as they were used by a nonnative teacher of English and five adult students of EFL. A qualitative analysis reveals that discourse markers fulfill a number of textual and interpersonal functions which may contribute greatly to the coherent and pragmatic flow of the discourse generated in classroom interaction.El artículo que aquí se presenta intenta investigar la interacción que ocurre en el aula de inglés como lengua extranjera cuando el profesor de inglés es nonativo. Un aspecto específico de la interacción en el aula y del uso del lenguaje es la presencia de los marcadores del discurso (MD. Con base en datos empíricos, este estudio pretende describir las ocurrencias, la frecuencia y las funciones principales de los MD. El análisis cualitativo de los datos revela que los MD cumplen funciones tanto textuales como interpersonales que pueden facilitar y contribuir al flujo coherente y pragmático del discurso generado en la interacción de aula.

  6. Establishing population distribution of drug-metabolizing enzyme activities for the use of salivary caffeine as a dynamic liver function marker in a Singaporean Chinese population.