Leveraging Algal Omics to Reveal Potential Targets for Augmenting TAG Accumulation

Energy Technology Data Exchange (ETDEWEB)

Guarnieri, Michael T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Pienkos, Philip T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Arora, Neha [Indian Institute of Technology Roorkee; Pruthi, Vikas [Indian Institute of Technology Roorkee; Poluri, Krishna Mohan [Indian Institute of Technology Roorkee

2018-04-18

Ongoing global efforts to commercialize microalgal biofuels have expedited the use of multi-omics techniques to gain insights into lipid biosynthetic pathways. Functional genomics analyses have recently been employed to complement existing sequence-level omics studies, shedding light on the dynamics of lipid synthesis and its interplay with other cellular metabolic pathways, thus revealing possible targets for metabolic engineering. Here, we review the current status of algal omics studies to reveal potential targets to augment TAG accumulation in various microalgae. This review specifically aims to examine and catalog systems level data related to stress-induced TAG accumulation in oleaginous microalgae and inform future metabolic engineering strategies to develop strains with enhanced bioproductivity, which could pave a path for sustainable green energy.

Role and potential of renewable energy and energy efficiency for global energy supply

Energy Technology Data Exchange (ETDEWEB)

Krewitt, Wolfram; Nienhaus, Kristina [German Aerospace Center e.V. (DLR), Stuttgart (Germany); Klessmann, Corinna; Capone, Carolin; Stricker, Eva [Ecofys Germany GmbH, Berlin (Germany); Graus, Wina; Hoogwijk, Monique [Ecofys Netherlands BV, Utrecht (Netherlands); Supersberger, Nikolaus; Winterfeld, Uta von; Samadi, Sascha [Wuppertal Institute for Climate, Environment and Energy GmbH, Wuppertal (Germany)

2009-12-15

The analysis of different global energy scenarios in part I of the report confirms that the exploitation of energy efficiency potentials and the use of renewable energies play a key role in reaching global CO2 reduction targets. An assessment on the basis of a broad literature research in part II shows that the technical potentials of renewable energy technologies are a multiple of today's global final energy consumption. The analysis of cost estimates for renewable electricity generation technologies and even long term cost projections across the key studies in part III demonstrates that assumptions are in reasonable agreement. In part IV it is shown that by implementing technical potentials for energy efficiency improvements in demand and supply sectors by 2050 can be limited to 48% of primary energy supply in IEA's ''Energy Technology Perspectives'' baseline scenario. It was found that a large potential for cost-effective measures exists, equivalent to around 55-60% of energy savings of all included efficiency measures (part V). The results of the analysis on behavioural changes in part VI show that behavioural dimensions are not sufficiently included in energy scenarios. Accordingly major research challenges are revealed. (orig.)

Proteome analysis reveals phosphorylation of ATP synthase beta -subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes

DEFF Research Database (Denmark)

Højlund, Kurt; Wrzesinski, Krzysztof; Larsen, Peter Mose

2003-01-01

quantitate a large number of proteins and their post-translational modifications simultaneously and is a powerful tool to study polygenic diseases like type 2 diabetes. Using this approach on human skeletal muscle biopsies, we have identified eight potential protein markers for type 2 diabetes in the fasting...... synthase beta-subunit phosphoisoform in diabetic muscle correlated inversely with fasting plasma glucose levels. These data suggest a role for phosphorylation of ATP synthase beta-subunit in the regulation of ATP synthesis and that alterations in the regulation of ATP synthesis and cellular stress proteins...

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

Science.gov (United States)

Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

2017-01-01

Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

Role and Potential of Direct Interspecies Electron Transfer in Anaerobic Digestion

Directory of Open Access Journals (Sweden)

Gahyun Baek

2018-01-01

Full Text Available Anaerobic digestion (AD is an effective biological treatment for stabilizing organic compounds in waste/wastewater and in simultaneously producing biogas. However, it is often limited by the slow reaction rates of different microorganisms’ syntrophic biological metabolisms. Stable and fast interspecies electron transfer (IET between volatile fatty acid-oxidizing bacteria and hydrogenotrophic methanogens is crucial for efficient methanogenesis. In this syntrophic interaction, electrons are exchanged via redox mediators such as hydrogen and formate. Recently, direct IET (DIET has been revealed as an important IET route for AD. Microorganisms undergoing DIET form interspecies electrical connections via membrane-associated cytochromes and conductive pili; thus, redox mediators are not required for electron exchange. This indicates that DIET is more thermodynamically favorable than indirect IET. Recent studies have shown that conductive materials (e.g., iron oxides, activated carbon, biochar, and carbon fibers can mediate direct electrical connections for DIET. Microorganisms attach to conductive materials’ surfaces or vice versa according to particle size, and form conductive biofilms or aggregates. Different conductive materials promote DIET and improve AD performance in digesters treating different feedstocks, potentially suggesting a new approach to enhancing AD performance. This review discusses the role and potential of DIET in methanogenic systems, especially with conductive materials for promoting DIET.

Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

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Dante Picchioni

2014-03-01

Full Text Available Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.

Selected soil enzymes: Examples of their potential roles in the ...

African Journals Online (AJOL)

Soil enzymes regulate ecosystem functioning and in particular play a key role in nutrient cycling. In this review we briefly summarise potential roles of selected enzymes such as amylase, arylsulphatases, -glucosidase, cellulose, chitinase, dehydrogenase, phosphatase, protease and urease in the ecosystem. We also ...

The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling.

Science.gov (United States)

Cupido, Tommaso; Rack, Paul G; Firestone, Ari J; Hyman, Joel M; Han, Kyuho; Sinha, Surajit; Ocasio, Cory A; Chen, James K

2009-01-01

Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

Potential protective role of hydrogen against cisplatininduced side ...

African Journals Online (AJOL)

Potential protective role of hydrogen against cisplatininduced side effects during chemotherapy: A mini-review of a novel hypothesis for antagonism of hydrogen. ... Molecular hydrogen has been shown to have therapeutic effects against damage to various organs (especially kidney, brain and liver) caused by ischemic ...

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

Science.gov (United States)

Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

Potential physiological role of plant glycosidase inhibitors

DEFF Research Database (Denmark)

Bellincampi, D.; Carmadella, L.; Delcour, J.A.

2004-01-01

Carbohydrate-active enzymes including glycosidases, transglycosidases, glycosyltransferases, polysaccharide lyases and carbohydrate esterases are responsible for the enzymatic processing of carbohydrates in plants. A number of carbohydrate-active enzymes are produced by microbial pathogens...... and insects responsible of severe crop losses. Plants have evolved proteinaceous inhibitors to modulate the activity of several of these enzymes. The continuing discovery of new inhibitors indicates that this research area is still unexplored and may lead to new exciting developments. To date, the role...... of the inhibitors is not completely understood. Here we review recent results obtained on the best characterised inhibitors, pointing to their possible biological role in vivo. Results recently obtained with plant transformation technology indicate that this class of inhibitors has potential biotechnological...

Potential ecological roles of flavonoids from Stellera chamaejasme.

Science.gov (United States)

Yan, Zhiqiang; Zeng, Liming; Jin, Hui; Qin, Bo

2015-01-01

Stellera chamaejasme L. (Thymelaeaceae), a perennial weed, distributes widely in the grasslands of Russia, Mongolia and China. The plant synthesizes various secondary metabolites including a group of flavonoids. To our knowledge, flavonoids play important roles in the interactions between plants and the environment. So, what are the benefits to S. chamaejasme from producing these flavonoids? Here, we discuss the potential ecological role of flavonoids from S. chamaejasme in protecting the plant from insects and other herbivores, as well as pathogens and competing plant species, and new data are provided on the phytotoxicity of flavonoids from S. chamaejasme toward Poa annua L.

A new set of ESTs from chickpea (Cicer arietinum L. embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

Directory of Open Access Journals (Sweden)

Shefali Gupta

Full Text Available Considering the economic importance of chickpea (C. arietinum L. seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

A new set of ESTs from chickpea (Cicer arietinum L.) embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

Science.gov (United States)

Gupta, Shefali; Garg, Vanika; Bhatia, Sabhyata

2015-01-01

Considering the economic importance of chickpea (C. arietinum L.) seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis.

Science.gov (United States)

Zheng, Wenning; Tan, Mui Fern; Old, Lesley A; Paterson, Ian C; Jakubovics, Nicholas S; Choo, Siew Woh

2017-06-07

Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.

Goldfish neurokinin B: Cloning, tissue distribution, and potential role in regulating reproduction.

Science.gov (United States)

Qi, Xin; Zhou, Wenyi; Li, Shuisheng; Liu, Yun; Ye, Gang; Liu, Xiaochun; Peng, Chun; Zhang, Yong; Lin, Haoran

2015-09-15

Neurokinin B (NKB) is a member of the tackykinin (TAC) family known to play a critical role in the neuroendocrine regulation of reproduction in mammals. However, its biological functions in teleosts are less clear. The aim of this study was to determine the role of NKB in fish reproduction using goldfish as a model. Two transcripts, TAC3a and TAC3b, which encode several NKBs, including NKBa-13, NKBa-10, NKBb-13, and NKBb-11, were cloned. Phylogenetic analysis revealed that NKBa-10 and NKBb-11 are closely related to mammalian NKB, while NKB-13s are more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that TAC3a and TAC3b mRNAs were mainly expressed in the brain. In situ hybridization further detected TAC3a and TAC3b mRNAs in several regions of the brain known to be involved in the regulation of reproduction and metabolism, as well as in the neurohypophysis of the pituitary. To investigate the potential role of NKBs in reproduction, goldfish were injected intraperitoneally with synthetic NKBa-13, -10, NKBb-13, or -11 peptides and the mRNA levels of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin subunits were measured. NKBa-13, -10, or NKBb-13, but not -11, significantly increased hypothalamic salmon GnRH and pituitary FSHβ and LHβ mRNA levels in both female and male goldfish. Finally, ovariectomy increased, while estradiol replacement reduced, TAC3a mRNA levels without affecting TAC3b expression in the hypothalamus. These data suggest that NKBa-13, -10, and NKBb-13 play a role in mediating the estrogen negative feedback regulation of gonadotropins. Copyright © 2014 Elsevier Inc. All rights reserved.

Metallothioneins in human tumors and potential roles in carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

2003-12-10

Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

Metallothioneins in human tumors and potential roles in carcinogenesis

International Nuclear Information System (INIS)

Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

2003-01-01

Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

The potential role of hydrogen energy in India and Western Europe

NARCIS (Netherlands)

van Ruijven, B.J.; Lakshmikanth, H.D.; van Vuuren, D.P.; de Vries, B.

2008-01-01

We used the TIMER energy model to explore the potential role of hydrogen in the energy systems of India and Western Europe, looking at the impacts on its main incentives: climate policy, energy security and urban air pollution. We found that hydrogen will not play a major role in both regions

Are all pharmacy staff interested in potential future roles?

Science.gov (United States)

Braund, Rhiannon; Chesney, Kate Marie; Keast, Emilia Paulina; Ng, Lye Jinn; Qi, Sarah; Samaranayaka, Sashika; Wang, Eddie

2012-12-01

To determine the current perceived roles and responsibilities of pharmacy staff in community pharmacies in New Zealand, and attitudes to proposed new advanced roles for pharmacy staff. Structured interviews were conducted within five community pharmacies, including at least two pharmacists, two dispensary staff and two pharmacy assistants. The interviews were structured to determine previous experience, current roles and responsibilities and the perceived future roles of pharmacy staff within a community pharmacy setting. Thematic analysis from 27 interviews identified key findings. Current roles appeared to be fairly well defined. Pharmacy assistants listed key roles as customer interactions and sales focus, noting that the dispensary was outside their area of responsibility. Technicians identified their role as being dispensary focused while pharmacists saw their role as the 'final check' to ensure accuracy as well as providing dispensing, counselling and managerial roles. With potential future roles, the assistants were less interested than the other groups, citing contentment with current situation and training as a barrier. Some technicians indicated an interest in furthering their roles, but many were reluctant and saw that additional training was too time consuming. Whilst pharmacists appeared to be interested in further scopes of practice, they appeared more reluctant to do this at the expense of handing dispensing responsibility to a non-pharmacist. Whilst there is a push for pharmacists to provide advanced clinical services, it is important to acknowledge that many staff working within community pharmacies are satisfied with their current role. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

The potential role of electrolytic hydrogen in Canada

International Nuclear Information System (INIS)

Hammerli, M.

1982-03-01

The potential role of electrolytic hydrogen in Canada is assessed for the period 1980 to 2025 for large-scale uses only. Present uses of hydrogen, and specifically electrolytic hydrogen, are discussed briefly and hydrogen production processes are summarized. Only hydrogen derived from natural gas, coal, or electrolysis of sater are considered. Cost estimates of electrolytic hydrogen are obtained from a parametric equation, comparing values for unipolar water elecctrklyser technologies with those for bipolar electrolysers. Both by-products of electrolytic hydrogen production, namely heavy water and oxygen, are evaluated. Electrolytic hydrogen, based on non-fossil primary energy sources, is also considered as ankther 'liquid fuel option' for Canada along with the alcohols. The market potential for hydrogen in general and electrolytic hydrogen is assessed. Results show that the market potential for electrolytic hydrogen is large by the year 2025

Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

Science.gov (United States)

Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

2014-01-01

Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

Directory of Open Access Journals (Sweden)

Patrick eFissler

2015-07-01

Full Text Available Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control, and second, educational learning experiences (e.g., studying foreign languages improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

Directory of Open Access Journals (Sweden)

James J Collins

Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

Science.gov (United States)

Staines, Katherine A; Javaheri, Behzad; Hohenstein, Peter; Fleming, Robert; Ikpegbu, Ekele; Unger, Erin; Hopkinson, Mark; Buttle, David J; Pitsillides, Andrew A; Farquharson, Colin

2017-11-01

The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn flox/flox (cKO) mice and their Pdpn flox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Harsh parenting and academic achievement in Chinese adolescents: Potential mediating roles of effortful control and classroom engagement.

Science.gov (United States)

Wang, Mingzhong; Deng, Xueli; Du, Xiuxiu

2018-04-01

This study examined (a) the potential mediating roles of effortful control and classroom engagement in the association between harsh parenting and adolescent academic achievement, and (b) the potential moderating role of gender. Sixth through eighth graders in rural China (n=815, mean age=12.55years) reported on harsh parenting, effortful control, and classroom engagement. Parents also reported on each other's harsh parenting. Academic achievement was assessed by students' test scores and teacher-rated academic performance. Results of structural equation modeling revealed gender differences in patterns of association among the model variables. Harsh parenting was negatively and directly associated with academic achievement for both boys and girls. It was also negatively and indirectly associated with academic achievement via effortful control and classroom engagement sequentially, forming a common indirect "path" for boys and girls. The indirect negative effect of harsh parenting on boys' academic achievement was mainly realized through the mediator of effortful control, whereas this same indirect effect for girls was mainly realized through the mediator of classroom engagement. Jointly, effortful control and classroom engagement precipitates more indirect effects for boys than for girls in the association between harsh parenting and academic achievement. The discussion analyzes the potential "paths" from harsh parenting to adolescent academic achievement, as well as gender differences in these "paths." The current study has implications for teachers and parents eager to improve students' classroom engagement and academic achievement. Copyright © 2017. Published by Elsevier Ltd.

Role of MicroRNA-1 in Human Cancer and Its Therapeutic Potentials

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Chao Han

2014-01-01

Full Text Available While the mechanisms of human cancer development are not fully understood, evidence of microRNA (miRNA, miR dysregulation has been reported in many human diseases, including cancer. miRs are small noncoding RNA molecules that regulate posttranscriptional gene expression by binding to complementary sequences in the specific region of gene mRNAs, resulting in downregulation of gene expression. Not only are certain miRs consistently dysregulated across many cancers, but they also play critical roles in many aspects of cell growth, proliferation, metastasis, apoptosis, and drug resistance. Recent studies from our group and others revealed that miR-1 is frequently downregulated in various types of cancer. Through targeting multiple oncogenes and oncogenic pathways, miR-1 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis and promotes apoptosis by ectopic expression. In this review, we highlight recent findings on the aberrant expression and functional significance of miR-1 in human cancers and emphasize its significant values for therapeutic potentials.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

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Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Potential protective role of bariatric surgery against breast cancer in postmenopausal women

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Irina Balescu

2017-05-01

Full Text Available Obesity is a major public health problem worldwide especially due to the metabolic disorders which seem to be induced by an excessive amount of adipose tissue. Therefore attention was focused on evaluating the role of bariatric surgery in order to offer a better control of the comorbidities such as diabetes mellitus, arterial hypertension or dyslipidemia which are widely accepted as causes of increased morbidity and mortality among obese patients. Once these benefits have been widely demonstrated, attention was focused on studying the potential protective role of bariatric surgery against development of various malignancies such a breast, endometrial, pancreatic or even colorectal cancer. This is a literature review regarding the potential protective role of bariatric surgery against breast cancer among obese women worldwide.

Linking child maltreatment history with child abuse potential: Relative roles of maltreatment types

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Mitkovic-Voncina Marija

2014-01-01

Full Text Available The independent roles of each childhood maltreatment type on child abuse potential in adults have been insufficiently explored and are inconsistent, with dissociation as one of the possible suggested mediators of intergenerational child abuse. We investigated these effects among 164 non-clinical adult parents, who filled in general questionnaires: Childhood Trauma Questionnaire (CTQ, Child Abuse Potential Inventory (CAPI and Dissociative Experience Scale (DES. Among all maltreatment types (emotional, physical and sexual abuse, emotional and physical neglect, emotional abuse was the only independent predictor in the regression model of child abuse potential. The relationship between emotional abuse history and child abuse potential was partially mediated by dissociation. The findings could speak in favor of the potentially unique detrimental role of emotional abuse in intergenerational maltreatment, with dissociation as one of the possible mechanisms.

The Potential Role of Artificial Intelligence Technology in Education.

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Salem, Abdel-Badeeh M.

The field of Artificial Intelligence (AI) and Education has traditionally a technology-based focus, looking at the ways in which AI can be used in building intelligent educational software. In addition AI can also provide an excellent methodology for learning and reasoning from the human experiences. This paper presents the potential role of AI in…

The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential

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Johannes Burtscher

2017-08-01

Full Text Available Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers, opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human

Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance.

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Barkla, Bronwyn J; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-12-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.

Do field-free electromagnetic potentials play a role in biology?

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Szasz, A; Vincze, G; Andocs, G; Szasz, O

2009-01-01

All bio-systems are imperfect dielectrics. Their general properties however cannot be described by conventional simple electrodynamics; the system is more complex. A central question in our present paper is centered on a controversial debate of the possible effect of the zero fields (only potentials exist). We show that the identical use of the "field-free," "curl-free," and "force-free" terminologies is incorrect, there have definitely different meanings. It is shown that the effective electro-dynamical parameters that describe and modify living systems are the potentials and not the fields. We discuss how the potentials have a role in biological processes even in field-free cases.

Carbon Turnover during Effluent Application to the Land: A Potential Role for Vegetation?

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Vasileios A. Tzanakakis

2015-01-01

Full Text Available This work investigates the effect of plant species (Eucalyptus camaldulensis vs. Arundo donax on carbon (C turnover during wastewater application to the land. The study was carried out in 40-liter pots under field conditions and plant species were treated either with pre-treated municipal wastewater or freshwater. Plant species had a strong effect on soil organic matter with pots planted with E. camaldulensis showing greater values than pots planted with A. donax. In accordance, greater respiration rates were measured in E. camaldulensis pots compared to those planted with A. donax. The respiration rate followed a decreasing trend with the progress of the season for both species. These findings suggest differences in soil microbial community composition and/or activity in the rhizosphere of plant species. Minor effects of plant species or effluent were observed in dissolved organic carbon, protein, and hexoses content. In conclusion, the results of the present study reveal an important role of plant species on C cycling in terrestrial environments with potential implications on the sequestration of C and release of nutrients and pollutants.

Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

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Claudia Männel

2017-02-01

Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

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Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2016-01-01

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and con...

Analysis of Large Seeds from Three Different Medicago truncatula Ecotypes Reveals a Potential Role of Hormonal Balance in Final Size Determination of Legume Grains

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Kaustav Bandyopadhyay

2016-09-01

Full Text Available Legume seeds are important as protein and oil source for human diet. Understanding how their final seed size is determined is crucial to improve crop yield. In this study, we analyzed seed development of three accessions of the model legume, Medicago truncatula, displaying contrasted seed size. By comparing two large seed accessions to the reference accession A17, we described mechanisms associated with large seed size determination and potential factors modulating the final seed size. We observed that early events during embryogenesis had a major impact on final seed size and a delayed heart stage embryo development resulted to large seeds. We also observed that the difference in seed growth rate was mainly due to a difference in embryo cell number, implicating a role of cell division rate. Large seed accessions could be explained by an extended period of cell division due to a longer embryogenesis phase. According to our observations and recent reports, we observed that auxin (IAA and abscisic acid (ABA ratio could be a key determinant of cell division regulation at the end of embryogenesis. Overall, our study highlights that timing of events occurring during early seed development play decisive role for final seed size determination.

Potential roles for transposable elements in creating imprinted expression.

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Anderson, Sarah N; Springer, Nathan M

2018-04-01

Changes in gene expression can have profound effects on phenotype. Nature has provided many complex patterns of gene regulation such as imprinting. Imprinted genes exhibit differences in the expression of the maternal and paternal alleles, even though they reside in the same nucleus with access to the same trans-acting factors. Significant attention has been focused on the potential reasons that imprinted expression could be beneficial and stabilized by selection. However, less attention has focused on understanding how imprinted expression might arise or decay. We discuss the evidence for frequent turnover of imprinted expression based on evolutionary analyses in plants and the potential role for transposable elements (TEs) in creating imprinted expression patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transient receptor potential channel superfamily: Role in lower urinary tract function.

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Ogawa, Teruyuki; Imamura, Tetsuya; Nakazawa, Masaki; Hiragata, Shiro; Nagai, Takashi; Minagawa, Tomonori; Yokoyama, Hitoshi; Ishikawa, Masakuni; Domen, Takahisa; Ishizuka, Osamu

2015-11-01

Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract. © 2015 The Japanese Urological Association.

Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

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Carine Bossard

Full Text Available Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb, phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.

Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

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Gaudin, Françoise; Machelon, Véronique; Brigitte, Madly; Jacquard, Carine; Pillon, Arnaud; Balaguer, Patrick; Balabanian, Karl; Lazennec, Gwendal

2012-01-01

Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients. PMID:22970307

Potential role of biotechnology tools for genetic improvement of “lost ...

African Journals Online (AJOL)

The paper considers the potential role of biotechnology applications like DNA markers in understanding the evolution, origin, distribution and diversity of fonio in Africa; somaclonal variation in generating genetic variability in fonio; and genetic transformation in circumventing fonio breeding barriers to introduce alien genes ...

The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.

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Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol

2015-01-01

The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.

Mast cells: potential positive and negative roles in tumor biology.

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Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

2013-11-01

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

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Huynh Truc

2007-12-01

Full Text Available Abstract Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18 that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

Ecological succession reveals potential signatures of marine-terrestrial transition in salt marsh fungal communities.

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Dini-Andreote, Francisco; Pylro, Victor Satler; Baldrian, Petr; van Elsas, Jan Dirk; Salles, Joana Falcão

2016-08-01

Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in β-diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal β-diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem.

Membrane potential correlates of sensory perception in mouse barrel cortex.

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Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

2013-11-01

Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

Potential role of p21 Activated Kinase 1 (PAK1) in the invasion and motility of oral cancer cells

International Nuclear Information System (INIS)

Parvathy, Muraleedharan; Sreeja, Sreeharshan; Kumar, Rakesh; Pillai, Madhavan Radhakrishna

2016-01-01

Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are potential therapeutic targets that are involved in numerous physiological functions. PAKs are serine-threonine kinases and they serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signalling, and cell-cycle progression. Although PAKs are known to play crucial roles in cancer progression, the role and clinical significance of PAKs in oral cancer remains poorly understood. Our results suggest that PAK1 is over-expressed in oral cancer cell lines. Stimulation of Oral Squamous Cell Carcinoma (OSCC) cells with serum growth factors leads to PAK1 re-localization and might cause a profound cytoskeletal remodelling. PAK1 was also found to be involved in the invasion, migration and cytoskeletal remodelling of OSCC cells. Our study revealed that PAK1 may play a crucial role in the progression of OSCC. Studying the role of PAK1 and its substrates is likely to enhance our understanding of oral carcinogenesis and potential therapeutic value of PAKs in oral cancer. The online version of this article (doi:10.1186/s12885-016-2263-8) contains supplementary material, which is available to authorized users

Potential Role of Extracellular Vesicles in the Pathophysiology of Drug Addiction.

Science.gov (United States)

Rao, P S S; O'Connell, Kelly; Finnerty, Thomas Kyle

2018-01-23

Extracellular vesicles (EVs) are small vesicles secreted by cells and are known to carry sub-cellular components including microRNA, proteins, and lipids. Due to their ability to transport cargo between cells, EVs have been identified as important regulators of various pathophysiological conditions and can therefore influence treatment outcomes. In particular, the significance of microRNAs in EV-mediated cell-cell communication is well-documented. While the influence of EVs and the cargo delivered by EVs has been extensively reviewed in other neurological disorders, the available literature on the potential role of EVs in the pathophysiology of drug addiction has not been reviewed. Hence, in this article, the known effects of commonly abused drugs (ethanol, nicotine, opiates, cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the potential role of drugs of abuse in affecting the delivery of EV-packaged microRNAs, and the subsequent impact on neuronal health and continued drug dependence, has been discussed.

MicroRNA profiling of antler stem cells in potentiated and dormant states and their potential roles in antler regeneration.

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Ba, Hengxing; Wang, Datao; Li, Chunyi

2016-04-01

MicroRNAs (miRNAs) can effectively regulate gene expression at the post-transcriptional level and play a critical role in tissue growth, development and regeneration. Our previous studies showed that antler regeneration is a stem cell-based process and antler stem cells reside in the periosteum of a pedicle, the permanent bony protuberance, from which antler regeneration takes place. Antlers are the only mammalian organ that can fully regenerate and hence provide a unique opportunity to identify miRNAs that are involved in organ regeneration. In the present study, we used next generation sequencing technology sequenced miRNAs of the stem cells derived from either the potentiated or the dormant pedicle periosteum. A population of both conserved and 20 deer-specific miRNAs was identified. These conserved miRNAs were derived from 453 homologous hairpin precursors across 88 animal species, and were further grouped into 167 miRNA families. Among them, the miR-296 is embryonic stem cell-specific. The potentiation process resulted in the significant regulation (>±2 Fold, q value cell potentiation process. This research has identified miRNAs that are associated either with the dormant or the potentiated antler stem cells and identified some target miRNAs for further research into their role played in mammalian organ regeneration.

IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

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Daniel A Rauch

Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity.

Science.gov (United States)

Dkhil, Mohamed A; Al-Quraishy, Saleh; Diab, Marwa M S; Othman, Mohamed S; Aref, Ahmed M; Abdel Moneim, Ahmed E

2014-12-01

This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity.

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Judit Remenyi

Full Text Available miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.

Biophysical characteristics reveal neural stem cell differentiation potential.

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Fatima H Labeed

Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

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Arman Kilic

2012-01-01

Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity

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Yoav Ben-Simon

2015-07-01

Full Text Available Neurotransmitter release probability (Pr largely determines the dynamic properties of synapses. While much is known about the role of presynaptic proteins in transmitter release, their specific contribution to synaptic plasticity is unclear. One such protein, tomosyn, is believed to reduce Pr by interfering with the SNARE complex formation. Tomosyn is enriched at hippocampal mossy fiber-to-CA3 pyramidal cell synapses (MF-CA3, which characteristically exhibit low Pr, strong synaptic facilitation, and pre-synaptic protein kinase A (PKA-dependent long-term potentiation (LTP. To evaluate tomosyn’s role in MF-CA3 function, we used a combined knockdown (KD-optogenetic strategy whereby presynaptic neurons with reduced tomosyn levels were selectively activated by light. Using this approach in mouse hippocampal slices, we found that facilitation, LTP, and PKA-induced potentiation were significantly impaired at tomosyn-deficient synapses. These findings not only indicate that tomosyn is a key regulator of MF-CA3 plasticity but also highlight the power of a combined KD-optogenetic approach to determine the role of presynaptic proteins.

Glucocorticoid: A potential role in microgravity-induced bone loss

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Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

2017-11-01

Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.

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Bartis, Domokos; Crowley, Louise E; D'Souza, Vijay K; Borthwick, Lee; Fisher, Andrew J; Croft, Adam P; Pongrácz, Judit E; Thompson, Richard; Langman, Gerald; Buckley, Christopher D; Thickett, David R

2016-04-14

CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in the pathogenesis of fibrotic diseases in Idiopathic Pulmonary Fibrosis (IPF). CD248 quantitative immunohistochemistry (IHC) was performed on lung samples from 22 IPF patients and its expression was assayed in cultured pulmonary fibroblasts and epithelial cells. Effects of CD248 silencing was evaluated on fibroblast proliferation and myofibroblast differentiation. IHC revealed strong CD248 expression in mesenchymal cells of normal lung structures such as pleura and adventitia but not in epithelium. Fibrotic areas showed markedly stronger staining than unaffected lung tissue. The extent of CD248 staining showed a significant negative correlation to lung function parameters FEV1, FVC, TLC, and TLCO (r2 > 0 · 35, p < 0 · 01). CD248 protein levels were significantly greater in IPF-derived lung fibroblasts vs normal lung fibroblasts (p < 0 · 01) and CD248 silencing significantly reduced the proliferation of lung fibroblasts, but did not affected myofibroblast differentiation. We conclude that CD248 overexpression is possibly involved in the pathogenesis of IPF and it has potential as a disease severity marker. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF.

Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

DEFF Research Database (Denmark)

Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

2011-01-01

and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

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Desgagnés Julie

2006-03-01

Full Text Available Abstract Background Chlorogenic acid (CHL, the most potent functional inhibitor of the microsomal glucose-6-phosphate translocase (G6PT, is thought to possess cancer chemopreventive properties. It is not known, however, whether any G6PT functions are involved in tumorigenesis. We investigated the effects of CHL and the potential role of G6PT in regulating the invasive phenotype of brain tumor-derived glioma cells. Results RT-PCR was used to show that, among the adult and pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit glucose-6-phosphatase (G6Pase-α but expressed G6Pase-β which, when coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic tissues such as brain. CHL inhibited U-87 cell migration and matrix metalloproteinase (MMP-2 secretion, two prerequisites for tumor cell invasion. Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate (S1P, a potent mitogen for glioblastoma multiform cells, as well as the rapid, S1P-induced extracellular signal-regulated protein kinase phosphorylation potentially mediated through intracellular calcium mobilization, suggesting that G6PT may also perform crucial functions in regulating intracellular signalling. Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the adenosine triphosphate (ATP-depleting agents 2-deoxyglucose and 5-thioglucose, a mechanism that may inhibit ATP-mediated calcium sequestration by G6PT. Conclusion We illustrate a new G6PT function in glioma cells that could regulate the intracellular signalling and invasive phenotype of brain tumor cells, and that can be targeted by the anticancer properties of CHL.

RECORDED-ROLE PLAY IN EFL CLASSROOM: A WAY OF MAXIMIZING STUDENTS‟ POTENTIAL IN SPEAKING

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Krismiyati Krismiyati

2017-04-01

Full Text Available Teaching English for non English Department students will be quite a challenge as the students have various background and interest. Handling those students in a big number in a class that requires them to speak is another impending challenge. This is an action research on role-play in English classroom for Information Technology students. This study tries to see whether recorded-role play could maximize students‘ potential in speaking. This study involved 30 students taking English course in Information Technology Faculty. The students were given a situation in which they had to act the role play. They drafted the role -play before they recorded it. The result shows that students felt less tense in acting the role. They also got more time to practice their pronunciation before recording. It even gave students who felt reluctant and shy in the class to actively participate. In addition, students could play around with the supporting background sound to show their creativity. Surprisingly, most students do their best to show their effort in their speaking as the end-product would be played in the classroom, even the most quiet students performed really well. Finally, this recorded-role play proved to be an effective way to maximize students‘ potential in speaking.

Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs.

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Uppal, Abhineet; Ferguson, Mark K; Posner, Mitchell C; Hellman, Samuel; Khodarev, Nikolai N; Weichselbaum, Ralph R

2014-08-01

Oligometastasis is a cancer disease state characterized by a limited number of metastatic tumors involving single or few organs and with biological properties that make them potentially amenable to locoregional antitumor therapy. Current clinical data show that they are potentially curable with surgical resection or/and radiotherapy. Yet, mechanisms of progression from primary tumor to oligometastasis, rather than to polymetastases, is lacking in detail. In the current review we focus on the role of micro-RNAs in the regulation of metastases development and the role they may play in the differentiation of oligometastatic from polymetastatic progression. We also discuss the analyses of metastatic samples from oligo-and polymetastatic patients, which suggest that oligometastasis is a distinct biologic entity regulated in part by micro-RNAs. In addition, a review of the known functions of oligometastatic-specific micro-RNAs suggest that they regulate multiple steps in the metastatic cascade, including epithelial-mesenchymal transition, tumor invasion, intravasation, distant vascular extravasation and proliferation in a distant organ. Understanding the role of micro-RNAs and their target genes in oligometastatic disease may allow for the development of targeted therapies to effectively conrol the spread of metastases.

Quantitative Proteomics of the Tonoplast Reveals a Role for Glycolytic Enzymes in Salt Tolerance[C][W

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Barkla, Bronwyn J.; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-01-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na+ sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H+-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H+-pump activity. PMID:20028841

The role of various parameters used in proximity potential in heavy ...

Indian Academy of Sciences (India)

inal proximity potential 1977 to remove the discrepancy between theory and data. ... In the present study, the main aim is to pin down the role of the above-stated parameters .... The height and position of the barrier are marked, respectively, as VB and RB. .... The small difference is not significant because of the uncertainties.

Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin

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Flynn, Jeffrey M.; Phan, Chi

2017-01-01

ABSTRACT Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa are a major cause of mortality in cystic fibrosis (CF) patients. Although this bacterium has been extensively studied for its virulence determinants, biofilm growth, and immune evasion mechanisms, comparatively little is known about the nutrient sources that sustain its growth in vivo. Respiratory mucins represent a potentially abundant bioavailable nutrient source, although we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate. However, given that P. aeruginosa, particularly in its biofilm mode of growth, is thought to grow slowly in vivo, the inefficient use of mucin glycoproteins may be relevant to its persistence within the CF airways. To this end, we used whole-genome fitness analysis, combining transposon mutagenesis with high-throughput sequencing, to identify genetic determinants required for P. aeruginosa growth using intact purified mucins as a sole carbon source. Our analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway and amino acid biosynthetic machinery are required for mucin utilization. Secondary analyses confirmed the simultaneous liberation and consumption of acetate during mucin degradation and revealed a central role for the extracellular proteases LasB and AprA. Together, these studies describe a molecular basis for mucin-based nutrient acquisition by P. aeruginosa and reveal a host-pathogen dynamic that may contribute to its persistence within the CF airways. PMID:28507068

Potential Role of Inorganic Confined Environments in Prebiotic Phosphorylation.

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Dass, Avinash Vicholous; Jaber, Maguy; Brack, André; Foucher, Frédéric; Kee, Terence P; Georgelin, Thomas; Westall, Frances

2018-03-05

A concise outlook on the potential role of confinement in phosphorylation and phosphate condensation pertaining to prebiotic chemistry is presented. Inorganic confinement is a relatively uncharted domain in studies concerning prebiotic chemistry, and even more so in terms of experimentation. However, molecular crowding within confined dimensions is central to the functioning of contemporary biology. There are numerous advantages to confined environments and an attempt to highlight this fact, within this article, has been undertaken, keeping in context the limitations of aqueous phase chemistry in phosphorylation and, to a certain extent, traditional approaches in prebiotic chemistry.

Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function.

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Gaier, Eric D; Eipper, Betty A; Mains, Richard E

2014-05-01

Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. © 2014 New York Academy of Sciences.

Gene expression profiling reveals new potential players of gonad differentiation in the chicken embryo.

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Gwenn-Aël Carré

Full Text Available BACKGROUND: In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s involved in gonad differentiation is still incomplete. METHODOLOGY/PRINCIPAL FINDINGS: With the aim of improving characterization of the molecular pathway(s involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. CONCLUSION/SIGNIFICANCE: This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors

Gene Expression Profiling Reveals New Potential Players of Gonad Differentiation in the Chicken Embryo

Science.gov (United States)

Carré, Gwenn-Aël; Couty, Isabelle; Hennequet-Antier, Christelle; Govoroun, Marina S.

2011-01-01

Background In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s) involved in gonad differentiation is still incomplete. Methodology/Principal Findings With the aim of improving characterization of the molecular pathway(s) involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein) and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. Conclusion/Significance This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors of chicken gonad

Ant-infecting Ophiocordyceps genomes reveal a high diversity of potential behavioral manipulation genes and a possible major role for enterotoxins

NARCIS (Netherlands)

De Bekker, Charissa; Ohm, Robin A.; Evans, Harry C.; Brachmann, Andreas; Hughes, David P

2017-01-01

Much can be gained from revealing the mechanisms fungal entomopathogens employ. Especially intriguing are fungal parasites that manipulate insect behavior because, presumably, they secrete a wealth of bioactive compounds. To gain more insight into their strategies, we compared the genomes of five

Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

Science.gov (United States)

Mielczarek, Ewelina; Blaszkowska, Joanna

2016-08-01

Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

Regulatory roles and therapeutic potential of microRNA in sarcoma.

Science.gov (United States)

Lim, Hui Jun; Yang, Jia-Lin

2016-01-01

MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation.

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Megas, Charilaos; Hatzivassiliou, Eudoxia G; Yin, Qian; Marinopoulou, Elli; Hadweh, Paul; Vignali, Dario A A; Mosialos, George

2011-05-01

TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF-κB by innate and adaptive immunity stimuli. TRAF6 consists of a highly conserved carboxyl terminal TRAF-C domain which is preceded by a coiled coil domain and an amino terminal region that contains a RING domain and a series of putative zinc-finger motifs. The TRAF-C domain contributes to TRAF6 oligomerization and mediates the interaction of TRAF6 with upstream signaling molecules whereas the RING domain comprises the core of the ubiquitin ligase catalytic domain. In order to identify structural elements that are important for TRAF6-induced NF-κB activation, mutational analysis of the TRAF-C and RING domains was performed. Alterations of highly conserved residues of the TRAF-C domain of TRAF6 did not affect significantly the ability of the protein to activate NF-κB. On the other hand a number of functionally important residues (L77, Q82, R88, F118, N121 and E126) for the activation of NF-κB were identified within the RING domain of TRAF6. Interestingly, several homologues of these residues in TRAF2 were shown to have a conserved functional role in TRAF2-induced NF-κB activation and lie at the dimerization interface of the RING domain. Finally, whereas alteration of Q82, R88 and F118 compromised both the K63-linked polyubiquitination of TRAF6 and its ability to activate NF-κB, alteration of L77, N121 and E126 diminished the NF-κB activating function of TRAF6 without affecting TRAF6 K63-linked polyubiquitination. Our results support a conserved functional role of the TRAF RING domain dimerization interface and a potentially necessary but insufficient role for RING-dependent TRAF6 K63-linked polyubiquitination towards NF-κB activation in cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Vitamin D and Cardiovascular Disease: Potential Role in Health Disparities

Science.gov (United States)

Artaza, Jorge N.; Contreras, Sandra; Garcia, Leah A.; Mehrotra, Rajnish; Gibbons, Gary; Shohet, Ralph; Martins, David; Norris, Keith C.

2012-01-01

Cardiovascular disease (CVD), which includes coronary artery disease and stroke, is the leading cause of mortality in the nation. Excess CVD morbidity and premature mortality in the African American community is one of the most striking examples of racial/ethnic disparities in health outcomes. African Americans also suffer from increased rates of hypovitaminosis D, which has emerged as an independent risk factor for all-cause and cardiovascular mortality. This overview examines the potential role of hypovitaminosis D as a contributor to racial and ethnic disparities in cardiovascular disease (CVD). We review the epidemiology of vitamin D and CVD in African Americans and the emerging biological roles of vitamin D in key CVD signaling pathways that may contribute to the epidemiological findings and provide the foundation for future therapeutic strategies for reducing health disparities. PMID:22102304

The role of spin-orbit potential in nuclear prolate-shape dominance

Energy Technology Data Exchange (ETDEWEB)

Takahara, Satoshi, E-mail: staka@ks.kyorin-u.ac.jp [Kyorin University, School of Medicine, Mitaka, Tokyo 181-8611 (Japan); Onishi, Naoki [University of Tokyo (Japan); University of Yamanashi (Japan); Shimizu, Yoshifumi R. [Department of Physics, Graduate School of Science, Kyushu University, Fukuoka 812-8581 (Japan); Tajima, Naoki [Department of Applied Physics, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507 (Japan)

2011-08-26

It is confirmed, in terms of the Woods-Saxon-Strutinsky method, that the spin-orbit potential plays a decisive role in the predominance of prolate deformation, which has been a long standing problem in nuclear physics. It is originated from the combined effects of the spin-orbit coupling and the diffused surface of the potential, in agreement with the previous work based on a more schematic Nilsson-Strutinsky method. The degree of prolate-shape dominance exhibits an oscillatory behavior with respect to the strength of spin-orbit potential and, the prolate-shape dominance is realized at the proper strength of the spin-orbit potential together with the standard surface diffuseness; this oscillatory behavior disappears in case of small diffuseness corresponding to ellipsoidal cavity. The calculated energy differences between oblate and prolate minima in this Letter are consistent with those of our extensive self-consistent calculations of the Hartree-Fock + BCS method with the Skyrme interaction.

The role of spin-orbit potential in nuclear prolate-shape dominance

International Nuclear Information System (INIS)

Takahara, Satoshi; Onishi, Naoki; Shimizu, Yoshifumi R.; Tajima, Naoki

2011-01-01

It is confirmed, in terms of the Woods-Saxon-Strutinsky method, that the spin-orbit potential plays a decisive role in the predominance of prolate deformation, which has been a long standing problem in nuclear physics. It is originated from the combined effects of the spin-orbit coupling and the diffused surface of the potential, in agreement with the previous work based on a more schematic Nilsson-Strutinsky method. The degree of prolate-shape dominance exhibits an oscillatory behavior with respect to the strength of spin-orbit potential and, the prolate-shape dominance is realized at the proper strength of the spin-orbit potential together with the standard surface diffuseness; this oscillatory behavior disappears in case of small diffuseness corresponding to ellipsoidal cavity. The calculated energy differences between oblate and prolate minima in this Letter are consistent with those of our extensive self-consistent calculations of the Hartree-Fock + BCS method with the Skyrme interaction.

Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology

Science.gov (United States)

Smith, Amy C.; Hristov, Kiril L.; Cheng, Qiuping; Xin, Wenkuan; Parajuli, Shankar P.; Earley, Scott; Malysz, John

2013-01-01

Members of the transient receptor potential (TRP) channel superfamily, including the Ca2+-activated monovalent cation-selective TRP melastatin 4 (TRPM4) channel, have been recently identified in the urinary bladder. However, their expression and function at the level of detrusor smooth muscle (DSM) remain largely unexplored. In this study, for the first time we investigated the role of TRPM4 channels in guinea pig DSM excitation-contraction coupling using a multidisciplinary approach encompassing protein detection, electrophysiology, live-cell Ca2+ imaging, DSM contractility, and 9-phenanthrol, a recently characterized selective inhibitor of the TRPM4 channel. Western blot and immunocytochemistry experiments demonstrated the expression of the TRPM4 channel in whole DSM tissue and freshly isolated DSM cells with specific localization on the plasma membrane. Perforated whole cell patch-clamp recordings and real-time Ca2+ imaging experiments with fura 2-AM, both using freshly isolated DSM cells, revealed that 9-phenanthrol (30 μM) significantly reduced the cation current and decreased intracellular Ca2+ levels. 9-Phenanthrol (0.1–30 μM) significantly inhibited spontaneous, 0.1 μM carbachol-induced, 20 mM KCl-induced, and nerve-evoked contractions in guinea pig DSM-isolated strips with IC50 values of 1–7 μM and 70–80% maximum inhibition. 9-Phenanthrol also reduced nerve-evoked contraction amplitude induced by continuous repetitive electrical field stimulation of 10-Hz frequency and shifted the frequency-response curve (0.5–50 Hz) relative to the control. Collectively, our data demonstrate the novel finding that TRPM4 channels are expressed in guinea pig DSM and reveal their critical role in the regulation of guinea pig DSM excitation-contraction coupling. PMID:23302778

Bacteriophage and their potential roles in the human oral cavity

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Anna Edlund

2015-04-01

Full Text Available The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts.

Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

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Potti Anil

2003-01-01

Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

Assessment of the Potential Role of Streptomyces in Cave Moonmilk Formation

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Marta Maciejewska

2017-06-01

Full Text Available Moonmilk is a karstic speleothem mainly composed of fine calcium carbonate crystals (CaCO3 with different textures ranging from pasty to hard, in which the contribution of biotic rock-building processes is presumed to involve indigenous microorganisms. The real microbial input in the genesis of moonmilk is difficult to assess leading to controversial hypotheses explaining the origins and the mechanisms (biotic vs. abiotic involved. In this work, we undertook a comprehensive approach in order to assess the potential role of filamentous bacteria, particularly a collection of moonmilk-originating Streptomyces, in the genesis of this speleothem. Scanning electron microscopy (SEM confirmed that indigenous filamentous bacteria could indeed participate in moonmilk development by serving as nucleation sites for CaCO3 deposition. The metabolic activities involved in CaCO3 transformation were furthermore assessed in vitro among the collection of moonmilk Streptomyces, which revealed that peptides/amino acids ammonification, and to a lesser extend ureolysis, could be privileged metabolic pathways participating in carbonate precipitation by increasing the pH of the bacterial environment. Additionally, in silico search for the genes involved in biomineralization processes including ureolysis, dissimilatory nitrate reduction to ammonia, active calcium ion transport, and reversible hydration of CO2 allowed to identify genetic predispositions for carbonate precipitation in Streptomyces. Finally, their biomineralization abilities were confirmed by environmental SEM, which allowed to visualize the formation of abundant mineral deposits under laboratory conditions. Overall, our study provides novel evidences that filamentous Actinobacteria could be key protagonists in the genesis of moonmilk through a wide spectrum of biomineralization processes.

Potential Role of Activating Transcription Factor 5 during Osteogenesis

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Luisa Vicari

2016-01-01

Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

Potential Role of Activating Transcription Factor 5 during Osteogenesis.

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Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

2016-01-01

Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

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Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

2013-02-01

Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

STOP-EVENT-RELATED POTENTIALS FROM INTRACRANIAL ELECTRODES REVEAL A KEY ROLE OF PREMOTOR AND MOTOR CORTICES IN STOPPING ONGOING MOVEMENTS

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Maurizio eMattia

2012-06-01

Full Text Available In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus. These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e. premotor (PMA and primary motor (M1 cortices. Electroencephalographic (EEG studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA and Brodmann's area (BA 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times. These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

OpenAIRE

Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.

2016-01-01

Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nocicep...

Mitigation potential and cost in tropical forestry - relative role for agroforestry

Energy Technology Data Exchange (ETDEWEB)

Makundi, Willy R.; Sathaye, Jayant A.

2004-01-01

This paper summarizes studies of carbon mitigation potential (MP) and costs of forestry options in seven developing countries with a focus on the role of agroforestry. A common methodological approach known as comprehensive mitigation assessment process (COMAP) was used in each study to estimate the potential and costs between 2000 and 2030. The approach requires the projection of baseline and mitigation land-use scenarios derived from the demand for forest products and forestland for other uses such as agriculture and pasture. By using data on estimated carbon sequestration, emission avoidance, costs and benefits, the model enables one to estimate cost effectiveness indicators based on monetary benefit per t C, as well as estimates of total mitigation costs and potential when the activities are implemented at equilibrium level. The results show that about half the MP of 6.9 Gt C (an average of 223 Mt C per year) between 2000 and 2030 in the seven countries could be achieved at a negative cost, and the other half at costs not exceeding $100 per t C. Negative cost indicates that non-carbon revenue is sufficient to offset direct costs of about half of the options. The agroforestry options analyzed bear a significant proportion of the potential at medium to low cost per t C when compared to other options. The role of agroforestry in these countries varied between 6% and 21% of the MP, though the options are much more cost effective than most due to the low wage or opportunity cost of rural labor. Agroforestry options are attractive due to the large number of people and potential area currently engaged in agriculture, but they pose unique challenges for carbon and cost accounting due to the dispersed nature of agricultural activities in the tropics, as well as specific difficulties arising from requirements for monitoring, verification, leakage assessment and the establishment of credible baselines.

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Biomarkers of Kidney Cancer.

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Song, Yimeng; Zhong, Lijun; Zhou, Juntuo; Lu, Min; Xing, Tianying; Ma, Lulin; Shen, Jing

2017-12-01

Renal cell carcinoma (RCC) is a malignant and metastatic cancer with 95% mortality, and clear cell RCC (ccRCC) is the most observed among the five major subtypes of RCC. Specific biomarkers that can distinguish cancer tissues from adjacent normal tissues should be developed to diagnose this disease in early stages and conduct a reliable prognostic evaluation. Data-independent acquisition (DIA) strategy has been widely employed in proteomic analysis because of various advantages, including enhanced protein coverage and reliable data acquisition. In this study, a DIA workflow is constructed on a quadrupole-Orbitrap LC-MS platform to reveal dysregulated proteins between ccRCC and adjacent normal tissues. More than 4000 proteins are identified, 436 of these proteins are dysregulated in ccRCC tissues. Bioinformatic analysis reveals that multiple pathways and Gene Ontology items are strongly associated with ccRCC. The expression levels of L-lactate dehydrogenase A chain, annexin A4, nicotinamide N-methyltransferase, and perilipin-2 examined through RT-qPCR, Western blot, and immunohistochemistry confirm the validity of the proteomic analysis results. The proposed DIA workflow yields optimum time efficiency and data reliability and provides a good choice for proteomic analysis in biological and clinical studies, and these dysregulated proteins might be potential biomarkers for ccRCC diagnosis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of 26 sphingomonad genomes reveals diverse environmental adaptations and biodegradative capabilities

DEFF Research Database (Denmark)

Aylward, Frank O.; McDonald, Bradon R.; Adams, Sandra M.

2013-01-01

to the genus Sphingobium. Our pan-genomic analysis of sphingomonads reveals numerous species-specific open reading frames (ORFs) but few signatures of genus-specific cores. The organization and coding potential of the sphingomonad genomes appear to be highly variable, and plasmid-mediated gene transfer...... and chromosome-plasmid recombination, together with prophage- and transposon-mediated rearrangements, appear to play prominent roles in the genome evolution of this group. We find that many of the sphingomonad genomes encode numerous oxygenases and glycoside hydrolases, which are likely responsible...... a basis for understanding the ecological strategies employed by sphingomonads and their role in environmental nutrient cycling....

Role of Family Resilience and Mindfulness in Addiction Potential of Students

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S Jalili Nikoo

2015-07-01

Full Text Available Background & aim: family and individual factors are involved in addiction potential. The aim of this research was to investigate the role of family resiliency (family communication and problem solving, utilizing social and economic resources, maintaining a positive outlook, family connectedness, family spirituality, ability to make meaning of adversity and mindfulness in addiction potential of students. Method: the research method used in the present study was correlation. A number of 399 students from Yasuj University in 2012-13 academic years were selected through a multi- stage cluster sampling method and responded to the Iranian scale of addiction potential, family resiliency questionnaire, and short form of Freiburg mindfulness inventory. Collected data were analyzed using Pearson correlation coefficient and Simultaneous regression. Results: A negative and significant correlation was seen between family resiliency and its dimensions with addiction potential (P>0.01. Between mindfulness and addiction preparation, a significant and negative correlation was observed (P>0.01. The results of simultaneous regression analysis showed that family residency and mindfulness could significantly predict 13% of variance of addiction potential. Conclusion: The results of this study indicated the importance of family resilience and mindfulness as personal and family variables in preparing addiction. Therefore, the family resilience and mindfulness skills training could decrease the addiction potential among students.

Canada's potential role in the Clean Development Mechanism

International Nuclear Information System (INIS)

Pape-Salmon, A.

2000-01-01

The role that Canada might play in the Kyoto Protocol's Clean Development Mechanism (CDM) is discussed. The CDM prescribes the way in which industrialized countries could create emission reduction credits for greenhouse gas emission reduction projects in developing countries which, in turn they could use to meet their own commitments and possibly reduce their cost of compliance with the Kyoto Protocol. While Canada does not see itself as a CDM project investor, it strongly supports private sector involvement in the CDM and believes that it has a role to play in assisting CDM investments by the Canadian private sector by facilitating desirable outcomes via international negotiations on the rules and modalities for the CDM which would minimize transaction costs; give prominence to aspects that Canada recognizes as necessary precursors to mobilizing private sector involvement in CDM activities; maximize the flexibility for use of the CDM; allow for conversion of credits between different Kyoto Mechanisms; allow for the certification of emissions sequestration from sinks; and maximize the environmental and sustainable development benefits of CDM projects. Canada also supports, along with the other members of the 'Umbrella group', the fewest possible restrictions and significant autonomy to the private sector to implement a variety of project activities in developing countries. This report provides a detailed examination of the Canadian government's views on the CDM, Canada's participation in international emission reduction projects, the factors that drive Canadian demand for greenhouse gas emission reduction offsets and the potential demand for CDM offsets, Canada's greenhouse gas emission inventory and projections, the approach of Canadian corporate investors in the CDM and Canadian technology and expertise in greenhouse gas emission reductions. Various appendices to the report contain further details on a number of cooperation agreements between Canada and other

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

Science.gov (United States)

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Potential role of viruses in white plague coral disease.

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Soffer, Nitzan; Brandt, Marilyn E; Correa, Adrienne M S; Smith, Tyler B; Thurber, Rebecca Vega

2014-02-01

White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review.

Science.gov (United States)

Melo, A D B; Silveira, H; Luciano, F B; Andrade, C; Costa, L B; Rostagno, M H

2016-01-01

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

Brain Signals of Face Processing as Revealed by Event-Related Potentials

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Ela I. Olivares

2015-01-01

Full Text Available We analyze the functional significance of different event-related potentials (ERPs as electrophysiological indices of face perception and face recognition, according to cognitive and neurofunctional models of face processing. Initially, the processing of faces seems to be supported by early extrastriate occipital cortices and revealed by modulations of the occipital P1. This early response is thought to reflect the detection of certain primary structural aspects indicating the presence grosso modo of a face within the visual field. The posterior-temporal N170 is more sensitive to the detection of faces as complex-structured stimuli and, therefore, to the presence of its distinctive organizational characteristics prior to within-category identification. In turn, the relatively late and probably more rostrally generated N250r and N400-like responses might respectively indicate processes of access and retrieval of face-related information, which is stored in long-term memory (LTM. New methods of analysis of electrophysiological and neuroanatomical data, namely, dynamic causal modeling, single-trial and time-frequency analyses, are highly recommended to advance in the knowledge of those brain mechanisms concerning face processing.

Jazz musicians reveal role of expectancy in human creativity.

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Przysinda, Emily; Zeng, Tima; Maves, Kellyn; Arkin, Cameron; Loui, Psyche

2017-12-01

Creativity has been defined as the ability to produce work that is novel, high in quality, and appropriate to an audience. While the nature of the creative process is under debate, many believe that creativity relies on real-time combinations of known neural and cognitive processes. One useful model of creativity comes from musical improvisation, such as in jazz, in which musicians spontaneously create novel sound sequences. Here we use jazz musicians to test the hypothesis that individuals with training in musical improvisation, which entails creative generation of musical ideas, might process expectancy differently. We compare jazz improvisers, non-improvising musicians, and non-musicians in the domain-general task of divergent thinking, as well as the musical task of preference ratings for chord progressions that vary in expectation while EEGs were recorded. Behavioral results showed for the first time that jazz musicians preferred unexpected chord progressions. ERP results showed that unexpected stimuli elicited larger early and mid-latency ERP responses (ERAN and P3b), followed by smaller long-latency responses (Late Positivity Potential) in jazz musicians. The amplitudes of these ERP components were significantly correlated with behavioral measures of fluency and originality on the divergent thinking task. Together, results highlight the role of expectancy in creativity. Copyright © 2017 Elsevier Inc. All rights reserved.

Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.

Science.gov (United States)

Ung, Timothy H; Madsen, Helen J; Hellwinkel, Justin E; Lencioni, Alex M; Graner, Michael W

2014-11-01

Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

The potential roles of T-type Ca2+ channels in motor coordination

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Young-Gyun ePark

2013-10-01

Full Text Available Specific behavioral patterns are expressed by complex combinations of muscle coordination. Tremors are simple behavioral patterns and are the focus of studies investigating motor coordination mechanisms in the brain. T-type Ca2+ channels mediate intrinsic neuronal oscillations and rhythmic burst spiking, and facilitate the generation of tremor rhythms in motor circuits. Despite substantial evidence that T-type Ca2+ channels mediate pathological tremors, their roles in physiological motor coordination and behavior remain unknown. Here, we review recent progress in understanding the roles that T-type Ca2+ channels play under pathological conditions, and discuss the potential relevance of these channels in mediating physiological motor coordination.

Characterization of calpastatin gene in fish: its potential role in muscle growth and fillet quality.

Science.gov (United States)

Salem, Mohamed; Yao, Jianbo; Rexroad, Caird E; Kenney, P Brett; Semmens, Kenneth; Killefer, John; Nath, Joginder

2005-08-01

Calpastatin (CAST), the specific inhibitor of the calpain proteases, plays a role in muscle growth and meat quality. In rainbow trout (RBT), we identified cDNAs coding for two CAST isoforms, a long (CAST-L) and a short isoform (CAST-S), apparently derived from two different genes. Zebrafish and pufferfish CAST cDNA and genomic sequences were retrieved from GenBank and their exon/intron structures were characterized. Fish CASTs are novel in that they have fewer repetitive inhibitory domains as compared to their mammalian counterparts (one or two vs. four). The expressions of CAST mRNAs were measured in three RBT strains with different growth rates and fillet firmness that were fed either high energy or control diets. CAST-L and S expressions were significantly lower (pfillet. Strain or diet did not affect level of calpain mRNAs. However, the decrease in the CAST/calpain ratio at the mRNA level did not lead to a corresponding change in the calpain catalytic activity. Further investigation should reveal a potential use of the CAST gene as a tool to monitor fish muscle growth and fillet firmness.

Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics.

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Jyh-Ying Peng

2011-10-01

Full Text Available Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology.

The potential role of hydrogen energy in India and Western Europe

International Nuclear Information System (INIS)

Ruijven, Bas van; Hari, Lakshmikanth; Vuuren, Detlef P. van; Vries, Bert de

2008-01-01

We used the TIMER energy model to explore the potential role of hydrogen in the energy systems of India and Western Europe, looking at the impacts on its main incentives: climate policy, energy security and urban air pollution. We found that hydrogen will not play a major role in both regions without considerable cost reductions, mainly in fuel cell technology. Also, energy taxation policy is essential for hydrogen penetration and India's lower energy taxes limit India's capacity to favour hydrogen. Once available to the (European) energy system, hydrogen can decrease the cost of CO 2 emission reduction by increasing the potential for carbon capture technology. However, climate policy alone is insufficient to speed up the transition. Hydrogen diversifies energy imports; especially for Europe it decreases oil imports, while increasing imports of coal and natural gas. For India, it provides an opportunity to decrease oil imports and use indigenous coal resources in the transport sector. Hydrogen improves urban air quality by shifting emissions from urban transport to hydrogen production facilities. However, for total net emissions we found a sensitive trade-off between lower emissions at end-use (in transport) and higher emissions from hydrogen production, depending on local policy for hydrogen production facilities

Working Sandwich Generation Women Utilize Strategies within and between Roles to Achieve Role Balance

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Girdler, Sonya J.

2016-01-01

Increasingly, women simultaneously balance the roles of mother, parental carer and worker. However, individual role balance strategies among these working ‘sandwich’ generation women have not been thoroughly explored. Eighteen women combining these three roles were interviewed about their individual role balance strategies. Findings were identified through the framework analysis technique, underpinned by the Model of Juggling Occupations. Achieving and maintaining role balance was explained as a complex process accomplished through a range of strategies. Findings revealed the women used six within-role balance strategies: living with integrity, being the best you can, doing what you love, loving what you do, remembering why and searching for signs of success. The women also described six between-role balance strategies: maintaining health and wellbeing, repressing perfectionism, managing time and energy, releasing responsibility, nurturing social connection and reciprocating. These findings provide a basis for health care providers to understand and potentially support working ‘sandwich’ generation women. PMID:27305074

Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

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Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

2008-06-25

Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

Taxonomy of the nuclear plant operator's role

International Nuclear Information System (INIS)

Kisner, R.A.; Fullerton, A.M.; Frey, P.R.; Dougherty, E.M.

1981-01-01

A program is presently under way at the Oak Ridge National Laboratory (ORNL) to define the functional design requirements of operational aids for nuclear power plant operators. A first and important step in defining these requirements is to develop an understanding of the operator's role or function. This paper describes a taxonomy of operator functions that applies during all operational modes and conditions of the plant. Other topics such as the influence of automation, role acceptance, and the operator's role during emergencies are also discussed. This systematic approach has revealed several areas which have potential for improving the operator's ability to perform his role

Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle.

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Mastan, Babu S; Kumari, Anchala; Gupta, Dinesh; Mishra, Satish; Kumar, Kota Arun

2014-06-01

Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten proteins that perform critical functions in Plasmodium life cycle. Except VII and VIII, functions of the remaining plasmepsin members have been well characterized. Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei using reverse genetics approach. Systematic comparison of growth kinetics and infection in both mosquito and vertebrate host revealed that PM VII depleted mutants exhibited no defects in development and progressed normally throughout the parasite life cycle. These studies suggest a dispensable role for PM VII in Plasmodium berghei life cycle. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

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Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

2013-01-01

Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude

Study on role structure in social planning systems

International Nuclear Information System (INIS)

Kimata, Noboru

1984-01-01

New proposals are attended with a new set of role-expectation. If we lack attention to this aspect of any proposal, we face a serious difficulty in its implementation stage. The system called as Public Hearring shows us this fact. In this paper, introducing ABC model of communication by Westley and Maclean, we try to describe a set of role-expectation for particitants in social planning systems. And also introducing analytical concepts of role enactment process, we reveal two important problems for any proposal as a subsystem of social planning systems: (i) importance of role negotiation process for role-consensus, and (ii) necessity of supporting systems for role-adaptation. Especially for role-adaptation to Channel-Roles, we indicate the potential of VISMS as its supporting system. (author)

Potential for tree rings to reveal spatial patterns of past drought variability across western Australia

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O'Donnell, Alison J.; Cook, Edward R.; Palmer, Jonathan G.; Turney, Chris S. M.; Grierson, Pauline F.

2018-02-01

Proxy records have provided major insights into the variability of past climates over long timescales. However, for much of the Southern Hemisphere, the ability to identify spatial patterns of past climatic variability is constrained by the sparse distribution of proxy records. This is particularly true for mainland Australia, where relatively few proxy records are located. Here, we (1) assess the potential to use existing proxy records in the Australasian region—starting with the only two multi-century tree-ring proxies from mainland Australia—to reveal spatial patterns of past hydroclimatic variability across the western third of the continent, and (2) identify strategic locations to target for the development of new proxy records. We show that the two existing tree-ring records allow robust reconstructions of past hydroclimatic variability over spatially broad areas (i.e. > 3° × 3°) in inland north- and south-western Australia. Our results reveal synchronous periods of drought and wet conditions between the inland northern and southern regions of western Australia as well as a generally anti-phase relationship with hydroclimate in eastern Australia over the last two centuries. The inclusion of 174 tree-ring proxy records from Tasmania, New Zealand and Indonesia and a coral record from Queensland did not improve the reconstruction potential over western Australia. However, our findings suggest that the addition of relatively few new proxy records from key locations in western Australia that currently have low reconstruction skill will enable the development of a comprehensive drought atlas for the region, and provide a critical link to the drought atlases of monsoonal Asia and eastern Australia and New Zealand.

A potential role for Drosophila mucins in development and physiology.

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Zulfeqhar A Syed

Full Text Available Vital vertebrate organs are protected from the external environment by a barrier that to a large extent consists of mucins. These proteins are characterized by poorly conserved repeated sequences that are rich in prolines and potentially glycosylated threonines and serines (PTS. We have now used the characteristics of the PTS repeat domain to identify Drosophila mucins in a simple bioinformatics approach. Searching the predicted protein database for proteins with at least 4 repeats and a high ST content, more than 30 mucin-like proteins were identified, ranging from 300-23000 amino acids in length. We find that Drosophila mucins are present at all stages of the fly life cycle, and that their transcripts localize to selective organs analogous to sites of vertebrate mucin expression. The results could allow for addressing basic questions about human mucin-related diseases in this model system. Additionally, many of the mucins are expressed in selective tissues during embryogenesis, thus revealing new potential functions for mucins as apical matrix components during organ morphogenesis.

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

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Priscila Daniele Ramos Cirilo

Full Text Available Uterine Leiomyomas (ULs are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs. Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC and gene expression microarrays (SAM. The CONEXIC algorithm was applied to integrate the data.The integrated analysis identified the top 30 significant genes (P<0.01, which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively and IGFBP5 (P = 0.0002 and P = 0.006, respectively were up-regulated in the tumours when compared with the adjacent normal myometrium.The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

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Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

2016-01-01

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Opening the Learning Process: The Potential Role of Feature Film in Teaching Employment Relations

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Lafferty, George

2016-01-01

This paper explores the potential of feature film to encourage more inclusive, participatory and open learning in the area of employment relations. Evaluations of student responses in a single postgraduate course over a five-year period revealed how feature film could encourage participatory learning processes in which students reexamined their…

High-resolution GPS tracking reveals habitat selection and the potential for long-distance seed dispersal by Madagascan flying foxes Pteropus rufus

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Ryszard Oleksy

2015-01-01

Full Text Available Long-distance seed dispersal can be important for the regeneration of forested habitats, especially in regions where deforestation has been severe. Old World fruit bats (Pteropodidae have considerable potential for long-distance seed dispersal. We studied the movement patterns and feeding behaviour of the endemic Madagascan flying fox Pteropus rufus, in Berenty Reserve, southeast Madagascar. Between July and September 2012 (the dry season nine males and six females were tagged with customised GPS loggers which recorded fixes every 2.5 min between 18.00 and 06.00 h. The combined home range of all of the tagged bats during 86 nights exceeded 58,000 ha. Females had larger home ranges and core foraging areas and foraged over longer distances (average 28.1 km; median 26.7 km than males (average 15.4 km; median 9.5 km. Because the study was conducted during the gestation period, the increased energy requirements of females may explain their greater mean foraging area. Compositional analysis revealed that bats show strong preferences for overgrown sisal (Agave sisalana plantations (a mix of shrub, trees and sisal plants and remnant riverside forest patches. Sisal nectar and pollen were abundant food sources during the tracking period and this probably contributed to the selective use of overgrown sisal plantations. The bats also ate large quantities of figs (Ficus grevei during the study, and dispersed seeds of this important pioneer species. The bats flew at an average speed of 9.13 m/s, perhaps to optimise gliding performance. The study confirms that P. rufus has the potential to be a long-distance seed disperser, and is able to fly over a large area, often crossing cleared parts of its habitat. It potentially plays an important role in the regeneration of threatened forest habitats in this biodiversity hotspot.

Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

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Michael Poulsen

2011-02-01

Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

The Potential Role(s) of Writing in Second Language Development

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Williams, Jessica

2012-01-01

Writing is often seen as having a minor role in second language learning. This article explores recent research that suggests that writing can have a facilitative role in language development. In particular, it focuses on three features of writing: (1) its slower pace, and (2) the enduring record that it leaves, both of which can encourage…

A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response.

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Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-03-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP-chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response.

A ChIP–chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response

Science.gov (United States)

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-01-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP–chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response. PMID:19129219

Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

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Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

2016-01-01

Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

Science.gov (United States)

Schell, Michael J.; Yang, Mingli; Teer, Jamie K.; Lo, Fang Yin; Madan, Anup; Coppola, Domenico; Monteiro, Alvaro N. A.; Nebozhyn, Michael V.; Yue, Binglin; Loboda, Andrey; Bien-Willner, Gabriel A.; Greenawalt, Danielle M.; Yeatman, Timothy J.

2016-01-01

Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC. PMID:27302369

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat

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Shumayla

2017-06-01

Full Text Available Long non-coding RNAs (lncRNAs are a family of regulatory RNAs that play essential role in the various developmental processes and stress responses. Recent advances in sequencing technology and computational methods enabled identification and characterization of lncRNAs in certain plant species, but they are less known in Triticum aestivum (bread wheat. Herein, we analyzed 52 RNA seq data (>30 billion reads and identified 44,698 lncRNAs in T. aestivum genome, which were characterized in comparison to the coding sequences (mRNAs. Similar to the mRNAs, lncRNAs were also derived from each sub-genome and chromosome, and showed tissue developmental stage specific and differential expression, as well. The modulated expression of lncRNAs during abiotic stresses like heat, drought, and salt indicated their putative role in stress response. The co-expression of lncRNAs with vital mRNAs including various transcription factors and enzymes involved in Abscisic acid (ABA biosynthesis, and gene ontology mapping inferred their regulatory roles in numerous biological processes. A few lncRNAs were predicted as precursor (19 lncRNAs, while some as target mimics (1,047 lncRNAs of known miRNAs involved in various regulatory functions. The results suggested numerous functions of lncRNAs in T. aestivum, and unfolded the opportunities for functional characterization of individual lncRNA in future studies.

Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity

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Hozeifa M. Hassan

2018-03-01

Full Text Available Tuberculosis (TB is one of the oldest infectious diseases that affected humankind and remains one of the world’s deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression

Crystal structure of the adenosine A _2A receptor bound to an antagonist reveals a potential allosteric pocket

Energy Technology Data Exchange (ETDEWEB)

Sun, Bingfa; Bachhawat, Priti; Chu, Matthew Ling-Hon; Wood, Martyn; Ceska, Tom; Sands, Zara A.; Mercier, Joel; Lebon, Florence; Kobilka, Tong Sun; Kobilka, Brian K. (Stanford-MED); (ConfometRx); (UCB Pharma)

2017-02-06

The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson’s disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A2A receptor bound to compound 1 (Cmpd-1), a novel A2AR/N-methyl D-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3.5 Å resolution. The A2A receptor with a cytochrome b562-RIL (BRIL) fusion (A2AR–BRIL) in the intracellular loop 3 (ICL3) was crystallized in detergent micelles using vapor-phase diffusion. Whereas A2AR–BRIL bound to the antagonist ZM241385 has previously been crystallized in lipidic cubic phase (LCP), structural differences in the Cmpd-1–bound A2AR–BRIL prevented formation of the lattice observed with the ZM241385–bound receptor. The crystals grew with a type II crystal lattice in contrast to the typical type I packing seen from membrane protein structures crystallized in LCP. Cmpd-1 binds in a position that overlaps with the native ligand adenosine, but its methoxyphenyl group extends to an exosite not previously observed in other A2AR structures. Structural analysis revealed that Cmpd-1 binding results in the unique conformations of two tyrosine residues, Tyr91.35 and Tyr2717.36, which are critical for the formation of the exosite. The structure reveals insights into antagonist binding that are not observed in other A2AR structures, highlighting flexibility in the binding pocket that may facilitate the development of A2AR-selective compounds for the treatment of Parkinson’s disease.

The role and potential of information technology in agricultural improvement

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Milovanović Slavoljub

2014-01-01

Full Text Available The agro-industrial sector in developing countriesis faced with challenges, such as requirement for increase of food production and yield and creation of opportunity for employment of rural and poor population. In addition, the agricultural sector is influenced by global factors and fast changes. These facts indicate that there is great need for information and information technologies (IT, which can be used to cope with the challenges and changes and to improve agricultural production and marketing. However, the potential of IT is not fully utilized in agriculture. Implementation of IT in agricultural sector and rural areas is relatively slow in comparison to the other sectors of the economy where contemporary IT has been implemented at high speed. The aim of the paper is to analyze role, potential and contribution of IT in agribusiness and to explain opportunities for use of IT in many fields of agricultural sector. Our findings are based on economic theory and available literature, and they suggest that IT has great potential for supporting farmers and the other stakeholders in improvement of efficiency, effectiveness and productivity of agriculture. However, the stakeholders have to cope with many limitations and problems in IT implementation and use.

The structure of SSO2064, the first representative of Pfam family PF01796, reveals a novel two-domain zinc-ribbon OB-fold architecture with a potential acyl-CoA-binding role

International Nuclear Information System (INIS)

Krishna, S. Sri; Aravind, L.; Bakolitsa, Constantina; Caruthers, Jonathan; Carlton, Dennis; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structure of SSO2064, the first structural representative of Pfam family PF01796 (DUF35), reveals a two-domain architecture comprising an N-terminal zinc-ribbon domain and a C-terminal OB-fold domain. Analysis of the domain architecture, operon organization and bacterial orthologs combined with the structural features of SSO2064 suggests a role involving acyl-CoA binding for this family of proteins. SSO2064 is the first structural representative of PF01796 (DUF35), a large prokaryotic family with a wide phylogenetic distribution. The structure reveals a novel two-domain architecture comprising an N-terminal, rubredoxin-like, zinc ribbon and a C-terminal, oligonucleotide/oligosaccharide-binding (OB) fold domain. Additional N-terminal helical segments may be involved in protein–protein interactions. Domain architectures, genomic context analysis and functional evidence from certain bacterial representatives of this family suggest that these proteins form a novel fatty-acid-binding component that is involved in the biosynthesis of lipids and polyketide antibiotics and that they possibly function as acyl-CoA-binding proteins. This structure has led to a re-evaluation of the DUF35 family, which has now been split into two entries in the latest Pfam release (v.24.0)

Schistosomiasis elimination strategies and potential role of a vaccine in achieving global health goals.

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Mo, Annie X; Agosti, Jan M; Walson, Judd L; Hall, B Fenton; Gordon, Lance

2014-01-01

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.

Science.gov (United States)

Naboulsi, Wael; Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Turewicz, Michael; Eisenacher, Martin; Voss, Don Marvin; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

2016-01-04

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

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Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Potential role of aromatase inhibitors in the treatment of endometriosis

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Abu Hashim H

2014-07-01

Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

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Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

2016-03-29

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.

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Zapotoczna, Marta; McCarthy, Hannah; Rudkin, Justine K; O'Gara, James P; O'Neill, Eoghan

2015-12-15

High-level resistance to antimicrobial drugs is a major factor in the pathogenesis of chronic Staphylococcus aureus biofilm-associated, medical device-related infections. Antimicrobial susceptibility analysis revealed that biofilms grown for ≤ 24 hours on biomaterials conditioned with human plasma under venous shear in iron-free cell culture medium were significantly more susceptible to antistaphylococcal antibiotics. Biofilms formed under these physiologically relevant conditions were regulated by SaeRS and dependent on coagulase-catalyzed conversion of fibrinogen into fibrin. In contrast, SarA-regulated biofilms formed on uncoated polystyrene in nutrient-rich bacteriological medium were mediated by the previously characterized biofilm factors poly-N-acetyl glucosamine, fibronectin-binding proteins, or autolytic activity and were antibiotic resistant. Coagulase-mediated biofilms exhibited increased antimicrobial resistance over time (>48 hours) but were always susceptible to dispersal by the fibrinolytic enzymes plasmin or nattokinase. Biofilms recovered from infected central venous catheters in a rat model of device-related infection were dispersed by nattokinase, supporting the important role of the biofilm phenotype and identifying a potentially new therapeutic approach with antimicrobials and fibrinolytic drugs, particularly during the early stages of device-related infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gene expression profiles of prohibitin in testes of Octopus tankahkeei (ot-phb) revealing its possible role during spermiogenesis.

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Mao, Hai-Tao; Wang, Da-Hui; Lan, Zhou; Zhou, Hong; Yang, Wan-Xi

2012-05-01

Prohibitin is essential for intracellular homeostasis and stabilization of mitochondrial respiratory chain complexes. To explore its functions during spermiogenesis of Octopus tankahkeei (O. tankahkeei), we have cloned and sequenced the cDNA of this mammalian PHB homologue (termed ot-PHB) from the testes of O. tankahkeei. The 1165 bp ot-phb cDNA contains a 100 bp 5' UTR, a 882 bp open reading frame and a 183 bp 3' UTR. The putative ot-PHB protein owns a transmembrane domain from 6 to 31 amino acid (aa) and a putative PHB domain from 26 to 178 aa. Protein alignment demonstrated that ot-PHB had 73.3, 73.6, 74.0, 75.1, and 45.4% identity with its homologues in Homo sapiens, Mus muculus, Danio rerio, Xenopus tropicalis and Trypanosoma brucei, respectively. Tissue distribution profile analysis revealed its presence in all the tissues examined. In situ hybridization in spermiogenic cells demonstrated that ot-phb was expressed moderately at the beginning of the spermiogenesis. The abundance of transcripts increased in intermediate spermatids and in drastically remodeling final spermatids. In mature spermatozoa, the residuary transcripts concentrated around the chondriosomal mantle where mitochondria assemble around. In summary, the expression of ot-phb during spermiogenesis implicates a potential function of this protein during mitochondrial ubiquitination. It is the first time to implicate the role of prohibitin in cephalopod spermiogenesis.

Cartilaginous Metabolomic Study Reveals Potential Mechanisms of Osteophyte Formation in Osteoarthritis.

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Xu, Zhongwei; Chen, Tingmei; Luo, Jiao; Ding, Shijia; Gao, Sichuan; Zhang, Jian

2017-04-07

Osteophyte is one of the inevitable consequences of progressive osteoarthritis with the main characteristics of cartilage degeneration and endochondral ossification. The pathogenesis of osteophyte formation is not fully understood to date. In this work, metabolomic approaches were employed to explore potential mechanisms of osteophyte formation by detecting metabolic variations between extracts of osteophyte cartilage tissues (n = 32) and uninvolved control cartilage tissues (n = 34), based on the platform of ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, as well as the use of multivariate statistic analysis and univariate statistic analysis. The osteophyte group was significantly separated from the control group by the orthogonal partial least-squares discriminant analysis models, indicating that metabolic state of osteophyte cartilage had been changed. In total, 28 metabolic variations further validated by mass spectrum (MS) match, tandom mass spectrum (MS/MS) match, and standards match mainly included amino acids, sulfonic acids, glycerophospholipids, and fatty acyls. These metabolites were related to some specific physiological or pathological processes (collagen dissolution, boundary layers destroyed, self-restoration triggered, etc.) which might be associated with the procedure of osteophyte formation. Pathway analysis showed phenylalanine metabolism (PI = 0.168, p = 0.004) was highly correlative to this degenerative process. Our findings provided a direction for targeted metabolomic study and an insight into further reveal the molecular mechanisms of ostophyte formation.

Exploring the Impact of Role-Playing on Peer Feedback in an Online Case-Based Learning Activity

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Ching, Yu-Hui

2014-01-01

This study explored the impact of role-playing on the quality of peer feedback and learners' perception of this strategy in a case-based learning activity with VoiceThread in an online course. The findings revealed potential positive impact of role-playing on learners' generation of constructive feedback as role-playing was associated with higher…

The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers.

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Jin, H; Wu, Y; Tan, X

2017-08-01

Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.

The potential protective role of taurine against experimental allergic inflammation.

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Nam, Sun-Young; Kim, Hyung-Min; Jeong, Hyun-Ja

2017-09-01

Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown. The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR) animal models. Here, the obtained results showed that taurine dose-dependently inhibited the production and mRNA expression of TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover, taurine brought a significant inhibition of the activities of NF-κB and caspase-1. In an OVA-induced AR animal model, the increased levels of nose rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1β were dramatically reduced by the administration of taurine. In summary, taurine could serve as potential novel remedy of allergic inflammatory disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxytocin--its role in male reproduction and new potential therapeutic uses.

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Thackare, Hemlata; Nicholson, Helen D; Whittington, Kate

2006-01-01

Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.

RNA Sequencing of Contaminated Seeds Reveals the State of the Seed Permissive for Pre-Harvest Aflatoxin Contamination and Points to a Potential Susceptibility Factor

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Josh Clevenger

2016-11-01

Full Text Available Pre-harvest aflatoxin contamination (PAC is a major problem facing peanut production worldwide. Produced by the ubiquitous soil fungus, Aspergillus flavus, aflatoxin is the most naturally occurring known carcinogen. The interaction between fungus and host resulting in PAC is complex, and breeding for PAC resistance has been slow. It has been shown that aflatoxin production can be induced by applying drought stress as peanut seeds mature. We have implemented an automated rainout shelter that controls temperature and moisture in the root and peg zone to induce aflatoxin production. Using polymerase chain reaction (PCR and high performance liquid chromatography (HPLC, seeds meeting the following conditions were selected: infected with Aspergillus flavus and contaminated with aflatoxin; and not contaminated with aflatoxin. RNA sequencing analysis revealed groups of genes that describe the transcriptional state of contaminated vs. uncontaminated seed. These data suggest that fatty acid biosynthesis and abscisic acid (ABA signaling are altered in contaminated seeds and point to a potential susceptibility factor, ABR1, as a repressor of ABA signaling that may play a role in permitting PAC.

RNA Sequencing of Contaminated Seeds Reveals the State of the Seed Permissive for Pre-Harvest Aflatoxin Contamination and Points to a Potential Susceptibility Factor

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Clevenger, Josh; Marasigan, Kathleen; Liakos, Vasileios; Sobolev, Victor; Vellidis, George; Holbrook, Corley; Ozias-Akins, Peggy

2016-01-01

Pre-harvest aflatoxin contamination (PAC) is a major problem facing peanut production worldwide. Produced by the ubiquitous soil fungus, Aspergillus flavus, aflatoxin is the most naturally occurring known carcinogen. The interaction between fungus and host resulting in PAC is complex, and breeding for PAC resistance has been slow. It has been shown that aflatoxin production can be induced by applying drought stress as peanut seeds mature. We have implemented an automated rainout shelter that controls temperature and moisture in the root and peg zone to induce aflatoxin production. Using polymerase chain reaction (PCR) and high performance liquid chromatography (HPLC), seeds meeting the following conditions were selected: infected with Aspergillus flavus and contaminated with aflatoxin; and not contaminated with aflatoxin. RNA sequencing analysis revealed groups of genes that describe the transcriptional state of contaminated vs. uncontaminated seed. These data suggest that fatty acid biosynthesis and abscisic acid (ABA) signaling are altered in contaminated seeds and point to a potential susceptibility factor, ABR1, as a repressor of ABA signaling that may play a role in permitting PAC. PMID:27827875

Helicobacter pylori Biofilm Formation and Its Potential Role in Pathogenesis.

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Hathroubi, Skander; Servetas, Stephanie L; Windham, Ian; Merrell, D Scott; Ottemann, Karen M

2018-06-01

Despite decades of effort, Helicobacter pylori infections remain difficult to treat. Over half of the world's population is infected by H. pylori , which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection, H. pylori localizes within the gastric mucosal layer, including deep within invaginations called glands; thanks to its impressive ability to survive despite the harsh acidic environment, it can persist for the host's lifetime. This ability to survive and persist in the stomach is associated with urease production, chemotactic motility, and the ability to adapt to the fluctuating environment. Additionally, biofilm formation has recently been suggested to play a role in colonization. Biofilms are surface-associated communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances. Biofilms pose a substantial health risk and are key contributors to many chronic and recurrent infections. This link between biofilm-associated bacteria and chronic infections likely results from an increased tolerance to conventional antibiotic treatments as well as immune system action. The role of this biofilm mode in antimicrobial treatment failure and H. pylori survival has yet to be determined. Furthermore, relatively little is known about the H. pylori biofilm structure or the genes associated with this mode of growth. In this review, therefore, we aim to highlight recent findings concerning H. pylori biofilms and the molecular mechanism of their formation. Additionally, we discuss the potential roles of biofilms in the failure of antibiotic treatment and in infection recurrence. Copyright © 2018 American Society for Microbiology.

Developing Effective Earthquake Risk Reduction Strategies: The Potential Role of Academic Institutions in Lebanon

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Baytiyeh, Hoda

2015-01-01

Lebanon faces the risk of powerful earthquakes with potentially devastating effects. However, the Lebanese people in general have not yet recognized this risk, as current educational programs and government officials have failed to inform them about it. This article discusses the essential role that Lebanese institutions of higher education should…

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

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Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy

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Vito Cucchiara

2017-01-01

Full Text Available Androgen receptor (AR signaling remains the major oncogenic pathway in prostate cancer (PCa. Androgen-deprivation therapy (ADT is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC. Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles involved in AR expression and their possible role as therapeutic targets.

TCGA bladder cancer study reveals potential drug targets

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Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

Role of potential scattering in the Shiba-Rusinov theory of the magnetic impurities in superconductors

International Nuclear Information System (INIS)

Okabe, Y.; Nagi, A.D.S.

1983-01-01

The Shiba-Rusinov theory of magnetic impurities in a superconductor is investigated, with special attention paid to the role of the potential scattering term in the electron-impurity interaction. The meaning of Anderson's theorem in the Shiba-Rusinov theory is discussed

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

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Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen

2016-08-01

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

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

Science.gov (United States)

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

2016-01-01

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

Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession.

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Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

2015-05-06

The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth's biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession.

Identification of metalloprotease/disintegrins in Xenopus laevis testis with a potential role in fertilization.

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Shilling, F M; Krätzschmar, J; Cai, H; Weskamp, G; Gayko, U; Leibow, J; Myles, D G; Nuccitelli, R; Blobel, C P

1997-06-15

Proteins containing a membrane-anchored metalloprotease domain, a disintegrin domain, and a cysteine-rich region (MDC proteins) are thought to play an important role in mammalian fertilization, as well as in somatic cell-cell interactions. We have identified PCR sequence tags encoding the disintegrin domain of five distinct MDC proteins from Xenopus laevis testis cDNA. Four of these sequence tags (xMDC9, xMDC11.1, xMDC11.2, and xMDC13) showed strong similarity to known mammalian MDC proteins, whereas the fifth (xMDC16) apparently represents a novel family member. Northern blot analysis revealed that the mRNA for xMDC16 was only expressed in testis, and not in heart, muscle, liver, ovaries, or eggs, whereas the mRNAs corresponding to the four other PCR products were expressed in testis and in some or all somatic tissues tested. The xMDC16 protein sequence, as predicted from the full-length cDNA, contains a metalloprotease domain with the active-site sequence HEXXH, a disintegrin domain, a cysteine-rich region, an EGF repeat, a transmembrane domain, and a short cytoplasmic tail. To study a potential role for these xMDC proteins in fertilization, peptides corresponding to the predicted integrin-binding domain of each protein were tested for their ability to inhibit X. laevis fertilization. Cyclic and linear xMDC16 peptides inhibited fertilization in a concentration-dependent manner, whereas xMDC16 peptides that were scrambled or had certain amino acid replacements in the predicted integrin-binding domain did not affect fertilization. Cyclic and linear xMDC9 peptides and linear xMDC13 peptides also inhibited fertilization similarly to xMDC16 peptides, whereas peptides corresponding to the predicted integrin-binding site of xMDC11.1 and xMDC11.2 did not. These results are discussed in the context of a model in which multiple MDC protein-receptor interactions are necessary for fertilization to occur.

The potential role of biomarkers in predicting gestational diabetes

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Huguette S Brink

2016-08-01

Full Text Available Gestational diabetes (GD is a frequent complication during pregnancy and is associated with maternal and neonatal complications. It is suggested that a disturbing environment for the foetus, such as impaired glucose metabolism during intrauterine life, may result in enduring epigenetic changes leading to increased disease risk in adult life. Hence, early prediction of GD is vital. Current risk prediction models are based on maternal and clinical parameters, lacking a strong predictive value. Adipokines are mainly produced by adipocytes and suggested to be a link between obesity and its cardiovascular complications. Various adipokines, including adiponectin, leptin and TNFα, have shown to be dysregulated in GD. This review aims to outline biomarkers potentially associated with the pathophysiology of GD and discuss the role of integrating predictive biomarkers in current clinical risk prediction models, in order to enhance the identification of those at risk.

Compressed-air energy storage: Commercialization potential and EPRI roles in the commercialization process

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Boyd, D. W.; Buckley, O. E.; Clark, C. E.

1982-12-01

This report describes an assessment of potential roles that EPRI might take to facilitate the commercial acceptance of compressed air energy storage (CAES) systems. The assessment is based on (1) detailed analyses of the market potential of utility storage technologies, (2) interviews with representatives of key participants in the CAES market, and (3) a decision analysis synthesizing much of the information about market and technology status. The results indicate a large potential market for CAES systems if the overall business environment for utilities improves. In addition, it appears that EPRI can have a valuable incremental impact in ensuring that utilities realize the potential of CAES by (1) continuing an aggressive information dissemination and technology transfer program, (2) working to ensure the success of the first United States CAES installation at Soyland Power Cooperative, (3) developing planning methods to allow utilities to evaluate CAES and other storage options more effectively and more realistically, and (4) supporting R and D to resolve residual uncertainties in first-generation CAES cost and performance characteristics.

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

International Nuclear Information System (INIS)

Teutschbein, Janka; Haydn, Johannes M; Samans, Birgit; Krause, Michael; Eilers, Martin; Schartl, Manfred; Meierjohann, Svenja

2010-01-01

Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

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Krause Michael

2010-07-01

Full Text Available Abstract Background Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1, early growth response 1 (Egr1, osteopontin (Opn, insulin-like growth factor binding protein 3 (Igfbp3, dual-specificity phosphatase 4 (Dusp4, and tumor-associated antigen L6 (Taal6. Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute

Potential role of nuclear power in developing and transition economies

International Nuclear Information System (INIS)

Ganiage, D.; Dierstein, P.

1995-01-01

The potential role of nuclear power is different in developing or in transition economies; in developing countries such as China, the growth of electricity consumption is high and the construction of several standardized plants is economically justified; in transitional economies, such as Ukraine, the needs are uncertain, old and unsafe plants have to be decommissioned and uncompleted nuclear plants (due to financial problems) should be completed. Nuclear power may provide the developing and transition economies with several advantages such as energy independence and fuel supply security, minimal environmental pollution, support to local industry and employment. It also means the support of national authorities and the development of a suitable infrastructure for plant safety and waste management, financial help and local population acceptance

The potential role of sclerostin in the development of osteoarthritis

DEFF Research Database (Denmark)

Shen, Jianlin; Lin, S.; Dong, Q

2016-01-01

Osteoarthritis (OA), a debilitating degenerative joint disease which is greatly influenced by alterations in the local mechanical loading environment in the joint. The exact aetiology of OA remains unknown, but loss of articular cartilage, subchondral sclerosis, and bone remodeling has been known...... and cartilage/subchondral in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients. © 2016, E-Century Publishing Corporation. All rights reserved....... of literatures have reported about the relation between Sclerostin and OA. In this review we have tried to summarize the current knowledge on the effect of Sclerostin and to explore the potential role of Sclerostin during the process of OA. A better understanding of the relationship between Sclerostin...

The potential role of carbon labeling in a green economy

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Cohen, Mark A.; Vandenbergh, Michael P.

2012-01-01

Over the past several years, labeling schemes that focus on a wide range of environmental and social metrics have proliferated. Although little empirical evidence has been generated yet with respect to carbon footprint labels, much can be learned from our experience with similar product labels. We first review the theory and evidence on the role of product labeling in affecting consumer and firm behavior. Next, we consider the role of governments and nongovernmental organizations, concluding that international, multistakeholder organizations have a critical part to play in setting protocols and standards. We argue that it is important to consider the entire life cycle of a product being labeled and develop an international standard for measurement and reporting. Finally, we examine the potential impact of carbon product labeling, discussing methodological and trade challenges and proposing a framework for choosing products best suited for labeling. - Highlights: ► Economic theory provides rationale for product information on carbon footprint. ► Small but growing evidence that labels will affect demand and product choice. ► International protocol using multi-stakeholder process is needed. ► Product priority should be based on life-cycle emissions and likely behavior changes. ► International trade law poses low risk for voluntary private carbon footprint labels.

Flavonoids and Wnt/β-Catenin Signaling: Potential Role in Colorectal Cancer Therapies

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Nathália G. Amado

2014-07-01

Full Text Available It is now well documented that natural products have played an important role in anticancer therapy. Many studies focus on the ability of these natural compounds to modulate tumor-related signaling pathways and the relationship of these properties to an anticancer effect. According to the World Health Organization (WHO, colorectal cancer (CRC is the third most common cancer and the fourth leading cause of cancer death among men and women. Therefore, finding strategies to fight against CRC is an emergent health problem. CRC has a strong association with deregulation of Wnt/β-catenin signaling pathway. As some types of natural compounds are capable of modulating the Wnt/β-catenin signaling, one important question is whether they could counteract CRC. In this review, we discuss the role of flavonoids, a class of natural compounds, on Wnt/β-catenin regulation and its possible potential for therapeutic usage on colorectal cancer.

Selenium: its potential role in male infertility

International Nuclear Information System (INIS)

Oguntibeju, O.O.; Esterhuyse, J.S.; Truter, E.J.

2009-01-01

Currently, biomedical research is showing interest in the anti-oxidant activity of selenium. This could be due to compelling evidence that reported that oxidative damage to cells and cell membranes is one of the causative agents in the pathogenesis of many disease states including male infertility. Selenium is a trace element which may be found in soil, water and some foods and is considered to be an essential element which plays an active role in several metabolic pathways and is believed to perform several important roles in the human body. These roles include anti-oxidative activities at cellular level and participating in different enzyme systems. Selenium also serves as a vital component in the maintenance of muscle cell and red blood cell integrity, playing a role in the synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It has also been reported that selenium is essential in the detoxification of toxic metals in the human system, foetal respiration and energy transfer reactions as well as in the production of sperm cells. It is thought that male infertility can be the result of a selenium deficiency as the absence of selenium in the testicular tissues induces degeneration which results in the active impairment of sperm motility as the first indication of impending infertility. This review paper investigates the role of selenium in male infertility. (author)

Potential Role of Metabolic Intervention in the Management of Advanced Differentiated Thyroid Cancer

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Sri Harsha Tella

2017-07-01

Full Text Available Well-differentiated thyroid carcinoma (DTC is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies. The role of vitamin C has been of interest again after a preclinical mice study showed that high-dose vitamin C is selectively lethal to KRAS and BRAF mutant colorectal cancer cells by targeting the glutathione pathway. This raises the possibility of utilizing high-doses of vitamin C in the treatment of aDTC where KRAS and BRAF mutations are common. Similarly, alteration of cellular metabolism by low-carbohydrate ketogenic diets can be an important therapeutic strategy to selectively kill cancer cells that mainly survive on glycolysis. Among the potential adjuvant therapies proposed in this paper, metformin is the only agent that has shown benefit in human model of aDTC, the others have shown benefit but in preclinical/animal studies only and need to be further evaluated in large clinical trials. In conclusion, in addition to concurrent chemotherapy options, these metabolic interventions may have a great potential as co-adjuvant therapy in the management of aDTC.

Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

International Nuclear Information System (INIS)

Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; Bedem, Henry van den; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis

When proteomics reveals unsuspected roles: the plastoglobule example

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Claire eBréhélin

2013-04-01

Full Text Available Plastoglobules are globular compartments found in plastids. Before initial proteomic studies were published, these particles were often viewed as passive lipid droplets whose unique role was to store lipids coming from the thylakoid turn-over, or to accumulate carotenoids in the chromoplasts. Yet, two proteomic studies, published concomitantly, suggested for the first time that plastoglobules are more than "junk cupboards" for lipids. Indeed, both studies demonstrated that plastoglobules do not only include structural proteins belonging to the plastoglobulin / fibrillin family, but also contain active enzymes. The specific plastoglobule localization of these enzymes has been confirmed by different approaches such as immunogold localization and GFP protein fusions, thus providing evidence that plastoglobules actively participate in diverse pathways of plastid metabolism. These proteomic studies have been the basis for numerous recent works investigating plastoglobule function. However, a lot still needs to be discovered about the molecular composition and the role of plastoglobules. In this chapter, we will describe how the proteomic approaches have launched new perspectives on plastoglobule functions.

Potential relationship between phenotypic and molecular characteristics in revealing livestock-associated Staphylococcus aureus in Chinese humans without occupational livestock contact

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Yanping Fan

2016-09-01

Full Text Available While some studies have defined Staphylococcus aureus based on its clonal complex and resistance pattern, few have explored the relations between the genetic lineages and antibiotic resistance patterns and immune evasion cluster (IEC genes. Our aim was to investigate the potential relationship between phenotypic and molecular characteristics so as to reveal livestock-associated S. aureus in humans. The study participants were interviewed, and they provided two nasal swabs for S. aureus analysis. All S. aureus and methicillin-resistant S. aureus (MRSA were tested for antibiotic susceptibility, multilocus sequence type and IEC genes. Of the 1162 participants, 9.3% carried S. aureus, including MRSA (1.4% and multidrug-resistant S. aureus (MDRSA, 2.8%. The predominant multidrug-resistant pattern among MDRSA isolates was nonsusceptibility to erythromycin, clindamycin and tetracycline. The most common S. aureus genotypes were ST7, ST6, ST188 and ST59, and the predominant MRSA genotype was ST7. Notably, the livestock-associated S. aureus isolates (IEC-negative CC9, IEC-negative tetracycline-resistant CC398, and IEC-negative tetracycline-resistant CC5 were found in people with no occupational livestock contact. These findings reveal a potential relationship between S. aureus CCs and IEC genes and antibiotic resistance patterns in defining livestock-associated S. aureus in humans and support growing concern about the potential livestock-to-human transmission of livestock-associated S. aureus by non-occupational livestock contact.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

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Annibali, Daniela; Whitfield, Jonathan R; Favuzzi, Emilia; Jauset, Toni; Serrano, Erika; Cuartas, Isabel; Redondo-Campos, Sara; Folch, Gerard; Gonzàlez-Juncà, Alba; Sodir, Nicole M; Massó-Vallés, Daniel; Beaulieu, Marie-Eve; Swigart, Lamorna B; Mc Gee, Margaret M; Somma, Maria Patrizia; Nasi, Sergio; Seoane, Joan; Evan, Gerard I; Soucek, Laura

2014-08-18

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

Movement patterns and dispersal potential of Pecos bluntnose shiner (Notropis simus pecosensis) revealed using otolith microchemistry

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Chase, Nathan M.; Caldwell, Colleen A.; Carleton, Scott A.; Gould, William R.; Hobbs, James A.

2015-01-01

Natal origin and dispersal potential of the federally threatened Pecos bluntnose shiner (Notropis simus pecosensis) were successfully characterized using otolith microchemistry and swimming performance trials. Strontium isotope ratios (87Sr:86Sr) of otoliths within the resident plains killifish (Fundulus zebrinus) were successfully used as a surrogate for strontium isotope ratios in water and revealed three isotopically distinct reaches throughout 297 km of the Pecos River, New Mexico, USA. Two different life history movement patterns were revealed in Pecos bluntnose shiner. Eggs and fry were either retained in upper river reaches or passively dispersed downriver followed by upriver movement during the first year of life, with some fish achieving a minimum movement of 56 km. Swimming ability of Pecos bluntnose shiner confirmed upper critical swimming speeds (Ucrit) as high as 43.8 cm·s−1 and 20.6 body lengths·s−1 in 30 days posthatch fish. Strong swimming ability early in life supports our observations of upriver movement using otolith microchemistry and confirms movement patterns that were previously unknown for the species. Understanding patterns of dispersal of this and other small-bodied fishes using otolith microchemistry may help redirect conservation and management efforts for Great Plains fishes.

RAS in the central nervous system: Potential role in neuropsychiatric disorders.

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Rocha, Natalia Pessoa; Simões e Silva, Ana Cristina; Prestes, Thiago Ruiz Rodrigues; Feracin, Victor; Machado, Caroline Amaral; Ferreira, Rodrigo Novaes; Teixeira, Antonio Lucio; de Miranda, Aline Silva

2018-02-25

The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders of the modulation of RAS. We carried out an extensive literature search in PubMed central. Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and haemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist communities of potential significance in biofouling.

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Liébana, Raquel; Arregui, Lucía; Belda, Ignacio; Gamella, Luis; Santos, Antonio; Marquina, Domingo; Serrano, Susana

2015-01-01

The yeast community was studied in a municipal full-scale membrane bioreactor wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts indicated that the activated sludge formed a suitable environment for them to proliferate, with cellular concentrations of 2.2 ± 0.8 × 10(3) CFU ml(-1). Sixteen species of seven genera were present in the biological reactor, with Ascomycetes being the most prevalent group (93%). Most isolates were able to grow in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop biofilms of variable complexity. The relationship between yeast populations and the protists in the MBR-WWTP was also studied, revealing that some protist species preyed on and ingested yeasts. These results suggest that yeast populations may play a role in the food web of a WWTP and, to some extent, contribute to membrane biofouling in MBR systems.

Poly(ADP-ribose polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

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Prashanth Komirishetty

2016-01-01

Full Text Available Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose polymerase (PARP upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.

Science.gov (United States)

Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2016-10-01

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Potential Role of Honey in Learning and Memory

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Zahiruddin Othman

2015-04-01

Full Text Available The composition and physicochemical properties of honey are variable depending on its floral source and often named according to the geographical location. The potential medicinal benefits of Tualang honey, a multifloral jungle honey found in Malaysia, have recently been attracting attention because of its reported beneficial effects in various diseases. This paper reviews the effects of honey, particularly Tualang honey, on learning and memory. Information regarding the effects of Tualang honey on learning and memory in human as well as animal models is gleaned to hypothesize its underlying mechanisms. These studies show that Tualang honey improves morphology of memory-related brain areas, reduces brain oxidative stress, increases brain-derived neurotrophic factor (BDNF and acetylcholine (ACh concentrations, and reduces acetylcholinesterase (AChE in the brain homogenates. Its anti-inflammatory roles in reducing inflammatory trigger and microglial activation have yet to be investigated. It is hypothesized that the improvement in learning and memory following Tualang honey supplementation is due to the significant improvement in brain morphology and enhancement of brain cholinergic system secondary to reduction in brain oxidative damage and/or upregulation of BDNF concentration. Further studies are imperative to elucidate the molecular mechanism of actions.

Heterogeneity of Systemic Oxidative Stress Profiles in COPD: A Potential Role of Gender

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Jonathan Maury

2015-01-01

Full Text Available Oxidative stress (OS plays a key role in the muscle impairment and exercise capacity of COPD patients. However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation. This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles. We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP levels in 54 stable COPD patients referred for a rehabilitation program. The main systemic antioxidant deficits in these patients concerned vitamins and trace elements. Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them. Interestingly, two patient profiles (clusters 3 and 4 had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx. Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity. Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses.

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance.

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Kos, Mark Z; Carless, Melanie A; Peralta, Juan; Curran, Joanne E; Quillen, Ellen E; Almeida, Marcio; Blackburn, August; Blondell, Lucy; Roalf, David R; Pogue-Geile, Michael F; Gur, Ruben C; Göring, Harald H H; Nimgaonkar, Vishwajit L; Gur, Raquel E; Almasy, Laura

2017-12-01

Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR < 0.1, association was detected for rs10941112 (p = 2.1 × 10 -5 ; q-value = 0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (p = 5.5 × 10 -4 ), including brain tissue data from the Genotype-Tissue Expression project (minimum p = 6.0 × 10 -5 ). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (p = 2.8 × 10 -5 ; q-value = 0.073). PPIs among our top gene-based association results (p < 0.05; n = 359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (p = 3.0 × 10 -5 ), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance. © 2017 Wiley Periodicals, Inc.

The Potential Role of Cache Mechanism for Complicated Design Optimization

International Nuclear Information System (INIS)

Noriyasu, Hirokawa; Fujita, Kikuo

2002-01-01

This paper discusses the potential role of cache mechanism for complicated design optimization While design optimization is an application of mathematical programming techniques to engineering design problems over numerical computation, its progress has been coevolutionary. The trend in such progress indicates that more complicated applications become the next target of design optimization beyond growth of computational resources. As the progress in the past two decades had required response surface techniques, decomposition techniques, etc., any new framework must be introduced for the future of design optimization methods. This paper proposes a possibility of what we call cache mechanism for mediating the coming challenge and briefly demonstrates some promises in the idea of Voronoi diagram based cumulative approximation as an example of its implementation, development of strict robust design, extension of design optimization for product variety

Beyond Gender Stereotypes in Language Comprehension: Self Sex-Role Descriptions Affect the Brain's Potentials Associated with Agreement Processing.

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Canal, Paolo; Garnham, Alan; Oakhill, Jane

2015-01-01

We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as "king" or "engineer") or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the Event Related Potential response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more "feminine" or "expressive" self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less "expressive" participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent.

Separable roles of UFO during floral development revealed by conditional restoration of gene function.

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Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

2003-02-01

The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy.

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Zhang, Jinlong; Lu, Xiaohui; Feng, Guijuan; Gu, Zhifeng; Sun, Yuyu; Bao, Guofeng; Xu, Guanhua; Lu, Yuanzhou; Chen, Jiajia; Xu, Lingfeng; Feng, Xingmei; Cui, Zhiming

2016-10-01

Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.

The Potential Role of Direct and Indirect Contacts on Infection Spread in Dairy Farm Networks.

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Gianluigi Rossi

2017-01-01

Full Text Available Animals' exchanges are considered the most effective route of between-farm infectious disease transmission. However, despite being often overlooked, the infection spread due to contaminated equipment, vehicles, or personnel proved to be important for several livestock epidemics. This study investigated the role of indirect contacts in a potential infection spread in the dairy farm network of the Province of Parma (Northern Italy. We built between-farm contact networks using data on cattle exchange (direct contacts, and on-farm visits by veterinarians (indirect contacts. We compared the features of the contact structures by using measures on static and temporal networks. We assessed the disease spreading potential of the direct and indirect network structures in the farm system by using data on the infection state of farms by paratuberculosis. Direct and indirect networks showed non-trivial differences with respect to connectivity, contact distribution, and super-spreaders identification. Furthermore, our analyses on paratuberculosis data suggested that the contributions of direct and indirect contacts on diseases spread are apparent at different spatial scales. Our results highlighted the potential role of indirect contacts in between-farm disease spread and underlined the need for a deeper understanding of these contacts to develop better strategies for prevention of livestock epidemics.

THE ROLE OF THE COMMERCIAL BANKS' CAPITAL IN REALIZATION OF INVESTMENT POTENTIAL OF BANKING SYSTEM OF UKRAINE

Directory of Open Access Journals (Sweden)

I. Lyutiy

2015-03-01

Full Text Available The article studies modern trends in investment corporate lending in Ukraine and the ultimate role of banking system in context of capital investments funding in Ukraine. The impact of structure and dynamics of commercial banks’ financial resources on realization of investment potential of Ukrainian banking system is analyzed. The role of banks’ capital adequacy as a precondition for expansion of investment corporate lending is determined.

Sex-role reversal of a monogamous pipefish without higher potential reproductive rate in females.

Science.gov (United States)

Sogabe, Atsushi; Yanagisawa, Yasunobu

2007-12-07

In monogamous animals, males are usually the predominant competitors for mates. However, a strictly monogamous pipefish Corythoichthys haematopterus exceptionally exhibits a reversed sex role. To understand why its sex role is reversed, we measured the adult sex ratio and the potential reproductive rate (PRR), two principal factors influencing the operational sex ratio (OSR), in a natural population of southern Japan. The adult sex ratio was biased towards females throughout the breeding season, but the PRR, which increased with water temperature, did not show sexual difference. We found that an alternative index of the OSR (Sf/Sm: sex ratio of 'time in') calculated from the monthly data was consistently biased towards females. The female-biased OSR associated with sex-role reversal has been reported in some polyandrous or promiscuous pipefish, but factors biasing the OSR differed between these pipefish and C. haematopterus. We concluded that the similar PRR between the sexes in C. haematopterus does not confer reproductive benefit of polygamous mating on either sex, resulting in strict monogamous mating, and its female-biased adult sex ratio promotes female-female competition for a mate, resulting in sex-role reversal.

Nonstructural leaf carbohydrates dynamics of Pinus edulis during drought-induced tree mortality reveal role for carbon metabolism in mortality mechanism

Science.gov (United States)

Adams, Henry D.; Germino, Matthew J.; Breshears, David D.; Barron-Gafford, Greg A.; Guardiola-Claramonte, Maite; Zou, Chris B.; Huxman, Travis E.

2013-01-01

* Vegetation change is expected with global climate change, potentially altering ecosystem function and climate feedbacks. However, causes of plant mortality, which are central to vegetation change, are understudied, and physiological mechanisms remain unclear, particularly the roles of carbon metabolism and xylem function.

Metal and Isotope Analysis of Bird Feathers in a Contaminated Estuary Reveals Bioaccumulation, Biomagnification, and Potential Toxic Effects.

Science.gov (United States)

Einoder, L D; MacLeod, C K; Coughanowr, C

2018-07-01

The Derwent estuary, in south east Tasmania, is highly contaminated with heavy metals, mainly due to past industrial pollution. This study sought to determine the extent of contamination, bioaccumulation, and biomagnification in the resident bird community and therefore to infer the potential for adverse effects in birds. Thirteen metals were measured from breast feathers (n = 51 individuals) of eight sympatric species of aquatic bird. Stable carbon (δ 13 C) and nitrogen (δ 15 N) isotopes were used to identify dietary sources of contaminants, trophic level, and potential biomagnification through food chains. Generalised linear models revealed that metal burdens were often poorly correlated with δ 13 C, indicating their uptake from a range of freshwater, brackish, and marine carbon sources-not surprising due to widespread contamination across the tidal estuary. Feather mercury increased significantly with trophic level (inferred from δ 15 N). White-bellied Sea-eagle Haliaeetus leucogaster samples contained 240 times more mercury than feral Goose Anser cygnoides. Feather arsenic and copper concentrations were significantly higher in birds feeding lower in the food chain. For several piscivorous species, both chick and adults were sampled revealing significantly higher feather mercury, zinc, and selenium in adults. Feathers from birds found dead along the banks of the estuary had significantly higher lead loads than from live birds, and numerous individuals had levels of mercury, zinc, and lead above toxic thresholds reported in other studies. These results highlight the need to include biota from higher trophic levels in contaminant monitoring programs to understand fully the fate and broader implications of contaminants in the environment.

The Potential Role of Yogurt in Weight Management and Prevention of Type 2 Diabetes.

Science.gov (United States)

Panahi, Shirin; Tremblay, Angelo

2016-01-01

Yogurt is a semisolid fermented milk product that originated centuries ago and is viewed as an essential food and important source of nutrients in the diet of humans. Over the last 30 years, overweight and obesity have become characteristic of Western and developing countries, which has led to deleterious health outcomes, including cardiovascular disease, type 2 diabetes, hypertension, and other chronic conditions. Recent epidemiological and clinical evidence suggests that yogurt is involved in the control of body weight and energy homeostasis and may play a role in reducing the risk for type 2 diabetes partly via the replacement of less healthy foods in the diet, its food matrix, the effect of specific nutrients such as calcium and protein on appetite control and glycemia, and alteration in gut microbiota. This review will discuss the specific properties that make yogurt a unique food among the dairy products, epidemiological and clinical evidence supporting yogurt's role in body weight, energy balance, and type 2 diabetes, including its potential mechanisms of action and gaps that need to be explored. Key teaching points • Several epidemiological and clinical studies have suggested a beneficial effect of yogurt consumption in the control of body weight and energy homeostasis, although this remains controversial. • Yogurt possesses unique properties, including its nutritional composition; lactic acid bacteria, which may affect gut microbiota; and food matrix, which may have a potential role in appetite and glycemic control. • Potential mechanisms of action of yogurt include an increase in body fat loss, decrease in food intake and increase in satiety, decrease in glycemic and insulin response, altered gut hormone response, replacement of less healthy foods, and altered gut microbiota. • The relative energy and nutrient content and contribution of a standard portion of yogurt to the overall diet suggest that the percentage daily intake of these nutrients

Sex-biased miRNAs in gonad and their potential roles for testis development in yellow catfish.

Science.gov (United States)

Jing, Jing; Wu, Junjie; Liu, Wei; Xiong, Shuting; Ma, Wenge; Zhang, Jin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

2014-01-01

Recently, YY super-male yellow catfish had been created by hormonal-induced sex reversal and sex-linked markers, which provides a promising research model for fish sex differentiation and gonad development, especially for testis development. MicroRNAs (miRNAs) have been revealed to play crucial roles in the gene regulation and gonad development in vertebrates. In this study, three small RNA libraries constructed from gonad tissues of XX female, XY male and YY super-male yellow catfish were sequenced. The sequencing data generated a total of 384 conserved miRNAs and 113 potential novel miRNAs, among which 23, 30 and 14 miRNAs were specifically detected in XX ovary, XY testis, and YY testis, respectively. We observed relative lower expression of several miR-200 family members, including miR-141 and miR-429 in YY testis compared with XY testis. Histological analysis indicated a higher degree of testis maturity in YY super-males compared with XY males, as shown by larger spermatogenic cyst, more spermatids and fewer spermatocytes in the spermatogenic cyst. Moreover, five miR-200 family members were significantly up-regulated in testis when treated by 17α-ethinylestradiol (EE2), high dose of which will impair testis development and cell proliferation. The down-regulation of miR-141 and 429 coincides with the progression of testis development in both yellow catfish and human. At last, the expression pattern of nine arbitrarily selected miRNAs detected by quantitative RT-PCR was consistent with the Solexa sequencing results. Our study provides a comprehensive miRNA transcriptome analysis for gonad of yellow catfish with different sex genotypes, and identifies a number of sex-biased miRNAs, some of that are potentially involved in testis development and spermatogenesis.

The role of social media in schizophrenia: evaluating risks, benefits, and potential.

Science.gov (United States)

Torous, John; Keshavan, Matcheri

2016-05-01

Patients with schizophrenia suffer from numerous social problems often because of negative symptoms of the illness and impairments in social cognition. Social media and social networks now offer a novel tool to engage and help patients navigate and potentially improve social functioning. In this review, we aim to explore how impaired neural networks in schizophrenia impair social functioning, examine the evidence base for social networks and social media to help in the role, consider the evidence for current risks and benefits of use, and discuss the future of social media and social networks for schizophrenia. Patients with schizophrenia are increasingly connected to and engaged with social media. There is strong evidence that they own, use, and accept digital tools like smartphones and already use social media services like Facebook at high rates, especially among those who are younger. Less is known about the clinical risks and benefits of social media use in schizophrenia, although there are increasingly more social networking platforms being designed specifically for those with mental illness. Social media tools have the potential to offer a plethora of new services to patients with schizophrenia, although the clinical evidence base for such is still nascent. It is important to ensure that both clinicians and patients are aware of and educated about the risks of using social media. Going forward, it is likely that social media will have an expanding role in care, with social media offering new pathways to address negative symptoms and impairments in social cognition in schizophrenia.

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

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Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

2015-10-13

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses

DEFF Research Database (Denmark)

Brok, J.; Thorlund, K.; Gluud, C.

2008-01-01

in 80% (insufficient information size). TSA(15%) and TSA(LBHIS) found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses had evidence of lack of effect. CONCLUSION: TSA reveals insufficient information size and potentially false positive results in many meta......OBJECTIVES: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries...... analogous to interim monitoring boundaries in a single trial. STUDY DESIGN AND SETTING: We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated information sizes and monitoring boundaries with three different anticipated intervention effects of 30% relative risk reduction (TSA...

Electrophysiological potentials reveal cortical mechanisms for mental imagery, mental simulation, and grounded (embodied cognition

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Haline E. Schendan

2012-09-01

Full Text Available Grounded cognition theory proposes that cognition, including meaning, is grounded in sensorimotor processing. The mechanism for grounding cognition is mental simulation, which is a type of mental imagery that re-enacts modal processing. To reveal top-down, cortical mechanisms for mental simulation of shape, event-related potentials were recorded to face and object pictures preceded by mental imagery of a picture. Mental imagery of the identical face or object (congruous condition facilitated not only categorical perception (VPP/N170 but also later visual knowledge (N3[00] complex and linguistic knowledge (N400 for faces more than objects, and strategic semantic analysis (late positive complex between 200 and 700 ms. The later effects resembled semantic congruity effects with pictures. Mental imagery also facilitated category decisions, as a P3(00 peaked earlier for congruous than incongruous (other category pictures, resembling the case when identical pictures repeat immediately. Thus mental imagery mimics semantic congruity and immediate repetition priming processes with pictures. Perception control results showed the opposite for faces and were in the same direction for objects: Perceptual repetition adapts (and so impairs processing of perceived faces from categorical perception onwards, but primes processing of objects during categorical perception, visual knowledge processes, and strategic semantic analysis. For both imagery and perception, differences between faces and objects support domain-specificity and indicate that cognition is grounded in modal processing. Altogether, this direct neural evidence reveals that top-down processes of mental imagery sustain an imagistic representation that mimics perception well enough to prime subsequent perception and cognition. This also suggests that automatic mental simulation of the visual shape of faces and objects operates between 200 and 400 ms, and strategic mental simulation operates between

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

Science.gov (United States)

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Potential role of propagule banks in the development of aquatic vegetation in backwaters along navigation canals

NARCIS (Netherlands)

Boedeltje, G; Bakker, JP; ter Heerdt, GNJ

The diversity and abundance of plant species in propagule banks of backwaters along two navigation canals in The Netherlands were studied in order to assess the relationship with the standing vegetation and the potential role of propagule banks in the establishment of (submerged) aquatic vegetation.

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

Science.gov (United States)

Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.;

Evaluating the potential of automated telephony systems in rural communities: Field assessment for project Lwazi of HLT Meraka

CSIR Research Space (South Africa)

Gumede, T

2008-11-01

Full Text Available the potential role automated telephony services in the improving access to important government information and services. Our interviews, focus groups and surveys revealed that an automated telephony service could be greatly support current government efforts...

The role of hypoxia in oral cancer and potentially malignant disorders: a review.

Science.gov (United States)

Kujan, Omar; Shearston, Kate; Farah, Camile S

2017-04-01

Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

Science.gov (United States)

Chen, Si; Knight, Walter E; Yan, Chen

2018-04-23

Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

Science.gov (United States)

Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

2014-12-01

2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression Patterns and Potential Biological Roles of Dip2a.

Directory of Open Access Journals (Sweden)

Luqing Zhang

Full Text Available Disconnected (disco-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles.

Exploring current and potential roles of Australian community pharmacists in gout management: a qualitative study.

Science.gov (United States)

Counsell, Allyce B; Nguyen, Amy D; Baysari, Melissa T; Kannangara, Diluk R W; McLachlan, Andrew J; Day, Richard O

2018-05-09

Gout is an increasingly prevalent form of inflammatory arthritis. Although effective treatments for gout exist, current management is suboptimal due to low medication adherence rates and treatments that are non-concordant with guidelines. Medications are the mainstay and most effective form of gout management. Thus, there is potential for community pharmacists to play an important primary health care role in gout management, however their current role and their potential to improve management of gout treatment is currently unclear. The purpose of the study is to explore the views of Australian pharmacists on their roles in gout management and to identify factors influencing their involvement in gout management. A convenience sample of community pharmacists were invited to participate using a snowballing recruitment strategy. Semi-structured, face-to-face interviews were conducted with 15 pharmacists of varying age, gender and pharmacy experience. Interviews focused on pharmacists' experiences of managing gout, interactions with people living with gout and their perceived roles and responsibilities in gout management. Interviews were transcribed verbatim and independently analysed by two reviewers to identify themes. The main role of pharmacists reported in gout management was providing patient education. The greatest facilitator to pharmacists involvement in gout management was identified to be pharmacists' good understanding of gout and its management. Barriers to pharmacists involvement were identified to be difficulties in monitoring adherence to gout medications, low priority given to gout in the pharmacy compared to other chronic health conditions, and lack of specific training and/or continuing education in gout prevention and management. Pharmacists can expand their primary health care role in gout management, particularly in the area of ongoing provision of education to people living with gout and in monitoring medication adherence in patients. However, a

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

Directory of Open Access Journals (Sweden)

Robin Hellerstedt

Full Text Available Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple. Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?. We investigated the event-related potential (ERP correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__ and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist. The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials

Science.gov (United States)

Hellerstedt, Robin; Johansson, Mikael

2016-01-01

Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit—Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit—Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks—Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation—Dentist). The participants’ memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

Science.gov (United States)

Hellerstedt, Robin; Johansson, Mikael

2016-01-01

Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist). The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring

Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

Science.gov (United States)

Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

2015-05-01

Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role Playing Game (RPG on nursing undergraduate course: educational potentials

Directory of Open Access Journals (Sweden)

Amanda Nathale Soares

2016-12-01

Full Text Available The objective of this study was to evaluate the potential of a Role Playing Game as an educational strategy in Undergraduate Nursing course, emphasizing its subjective implications in understanding aspects of the profession. This is a qualitative study, conducted through an evaluative research, of deployment analysis type. Nursing students of the 3rd period participated. The instrument to collection was Memories of Game, reports prepared by students after game sessions. The game is a non-traditional educational strategy that enabled approach to students through professional practice, active participation, self-reflection and reflection on professional practice. This strategy favored individualization processes, allowing students to experience situations similar to the nursing practice and exercise skills such as teamwork and creativity. The expansion of studies that address the subjective processes in higher education, through simulation games, can contribute to better design of health development processes.

Relationship of C-reactive protein, metabolic syndrome and diabetes mellitus: potential role of statins.

Science.gov (United States)

Nash, David T

2005-12-01

Atherosclerosis and the metabolic derangements of insulin resistance, metabolic syndrome and diabetes mellitus are all associated with underlying inflammatory processes. C-reactive protein (CRP), a marker of inflammation, has been shown to be a strong independent predictor of vascular events. It adds to cardiovascular disease risk at all levels of low-density-lipoprotein cholesterol and Framingham risk scores, and elevated levels are also associated with increasing severity of the metabolic syndrome. The development of a simple, stable, noninvasive test to measure high-sensitivity CRP has provided a clinical tool that may have an important role in the identification and assessment of individuals likely to develop cardiovascular or metabolic disease. The role of CRP in predicting cardiovascular risk is less clear in African Americans, however, than in white populations. Statins and thiazolidinediones are being investigated for their potential role in the prevention and treatment of the inflammatory processes involved in the metabolic syndrome and cardiovascular disease. In the future, assessment of CRP levels may contribute importantly to clinical decision-making in reducing cardiovascular risk.

Comparative analysis of CDPK family in maize, Arabidopsis, rice and sorghum revealed potential targets for drought tolerance improvement

Science.gov (United States)

Mittal, Shikha; Mallikarjuna, Mallana Gowdra; Rao, Atmakuri R.; Jain, Prashant A.; Dash, Prasanta K.; Thirunavukkarasu, Nepolean

2017-12-01

Calcium dependent protein kinases (CDPKs) play major role in regulation of plant growth and development in response to various stresses including drought. A set of 32 CDPK genes identified in maize were further used for searching of orthologs in the model plant Arabidopsis (72) and major food crops such as rice (78) and sorghum (91). We comprehensively investigated the phylogenetic relationship, annotations, gene duplications, gene structure, divergence time, 3-D protein structures and tissue-specific drought induced expression of CDPK genes in all four species. Variation in intron frequency among these species likely contributed to the functional diversity of CDPK genes to various stress responses. Protein kinase and protein kinase C phosphorylation site domains were the most conserved motifs identified in all species. Four groups were identified from the sequence-based phylogenetic analysis, in which maize CDPKs were clustered in group III. The time of divergence (Ka/Ks) analysis revealed that the CDPKs were evolved through stabilizing selection. Expression data showed that the CDPK genes were highly expressed in leaf of maize, rice, and sorghum whereas in Arabidopsis the maximum expression was observed in root. 3-D protein structure were predicted for the nine genes (Arabidopsis: 2, maize: 2, rice: 3 and sorghum: 2) showing differential expression in at least three species. The predicted 3-D structures were further evaluated and validated by Ramachandran plot, ANOLEA, ProSA and Verify-3D. The superimposed 3-D structure of drought-related orthologous proteins retained similar folding pattern owing to their conserved nature. Functional annotation revealed the involvement of CDPK genes in various pathways such as osmotic homeostasis, cell protection and root growth. The interactions of CDPK genes in various pathways play crucial role in imparting drought tolerance through different ABA and MAPK signalling cascades. Our studies suggest that these selected candidate

Analyses of Catharanthus roseus and Arabidopsis thaliana WRKY transcription factors reveal involvement in jasmonate signaling.

Science.gov (United States)

Schluttenhofer, Craig; Pattanaik, Sitakanta; Patra, Barunava; Yuan, Ling

2014-06-20

To combat infection to biotic stress plants elicit the biosynthesis of numerous natural products, many of which are valuable pharmaceutical compounds. Jasmonate is a central regulator of defense response to pathogens and accumulation of specialized metabolites. Catharanthus roseus produces a large number of terpenoid indole alkaloids (TIAs) and is an excellent model for understanding the regulation of this class of valuable compounds. Recent work illustrates a possible role for the Catharanthus WRKY transcription factors (TFs) in regulating TIA biosynthesis. In Arabidopsis and other plants, the WRKY TF family is also shown to play important role in controlling tolerance to biotic and abiotic stresses, as well as secondary metabolism. Here, we describe the WRKY TF families in response to jasmonate in Arabidopsis and Catharanthus. Publically available Arabidopsis microarrays revealed at least 30% (22 of 72) of WRKY TFs respond to jasmonate treatments. Microarray analysis identified at least six jasmonate responsive Arabidopsis WRKY genes (AtWRKY7, AtWRKY20, AtWRKY26, AtWRKY45, AtWRKY48, and AtWRKY72) that have not been previously reported. The Catharanthus WRKY TF family is comprised of at least 48 members. Phylogenetic clustering reveals 11 group I, 32 group II, and 5 group III WRKY TFs. Furthermore, we found that at least 25% (12 of 48) were jasmonate responsive, and 75% (9 of 12) of the jasmonate responsive CrWRKYs are orthologs of AtWRKYs known to be regulated by jasmonate. Overall, the CrWRKY family, ascertained from transcriptome sequences, contains approximately 75% of the number of WRKYs found in other sequenced asterid species (pepper, tomato, potato, and bladderwort). Microarray and transcriptomic data indicate that expression of WRKY TFs in Arabidopsis and Catharanthus are under tight spatio-temporal and developmental control, and potentially have a significant role in jasmonate signaling. Profiling of CrWRKY expression in response to jasmonate treatment

Genome-Resolved Metagenomic Analysis Reveals Roles for Candidate Phyla and Other Microbial Community Members in Biogeochemical Transformations in Oil Reservoirs.

Science.gov (United States)

Hu, Ping; Tom, Lauren; Singh, Andrea; Thomas, Brian C; Baker, Brett J; Piceno, Yvette M; Andersen, Gary L; Banfield, Jillian F

2016-01-19

Oil reservoirs are major sites of methane production and carbon turnover, processes with significant impacts on energy resources and global biogeochemical cycles. We applied a cultivation-independent genomic approach to define microbial community membership and predict roles for specific organisms in biogeochemical transformations in Alaska North Slope oil fields. Produced water samples were collected from six locations between 1,128 m (24 to 27°C) and 2,743 m (80 to 83°C) below the surface. Microbial community complexity decreased with increasing temperature, and the potential to degrade hydrocarbon compounds was most prevalent in the lower-temperature reservoirs. Sulfate availability, rather than sulfate reduction potential, seems to be the limiting factor for sulfide production in some of the reservoirs under investigation. Most microorganisms in the intermediate- and higher-temperature samples were related to previously studied methanogenic and nonmethanogenic archaea and thermophilic bacteria, but one candidate phylum bacterium, a member of the Acetothermia (OP1), was present in Kuparuk sample K3. The greatest numbers of candidate phyla were recovered from the mesothermic reservoir samples SB1 and SB2. We reconstructed a nearly complete genome for an organism from the candidate phylum Parcubacteria (OD1) that was abundant in sample SB1. Consistent with prior findings for members of this lineage, the OD1 genome is small, and metabolic predictions support an obligately anaerobic, fermentation-based lifestyle. At moderate abundance in samples SB1 and SB2 were members of bacteria from other candidate phyla, including Microgenomates (OP11), Atribacteria (OP9), candidate phyla TA06 and WS6, and Marinimicrobia (SAR406). The results presented here elucidate potential roles of organisms in oil reservoir biological processes. The activities of microorganisms in oil reservoirs impact petroleum resource quality and the global carbon cycle. We show that bacteria

Linearized potential vorticity mode and its role in transition to baroclinic instability

International Nuclear Information System (INIS)

Pieri, Alexandre; Salhi, Aziz; Cambon, Claude; Godeferd, Fabien

2011-01-01

Stratified shear flows have been studied using Rapid Distortion Theory (RDT) and DNS. If this flow is in addition subjected to vertical rotation, a slaved horizontal stratification is forced and baroclinic instability can occur. In this context, the RDT analysis shows an extention of the unstable domain up to a Richardson number Ri of 1. This work is completed here with new results on transition to baroclinic instability. Especially, the role of k x ≈ 0 modes (small streamwise wavenumbers) and the importance of coupling with the potential vorticity mode u (Ω pot ) is shown to be determinant for dramatic transient growth at intermediate times.

Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes

OpenAIRE

Zhou, Dongbo; Xie, Mingxuan; He, Baimei; Gao, Ying; Yu, Qiao; He, Bixiu; Chen, Qiong

2017-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non-coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re-annotation of NSCLC microarray data analysis profiling. The potential func...

Potential role of a cognitive rehabilitation program following left temporal lobe epilepsy surgery

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Camila de Vasconcelos Geraldi

Full Text Available ABSTRACT Research into memory and epilepsy has focused on measuring problems and exploring causes with limited attention directed at the role of neuropsychological rehabilitation in alleviating post-operative memory difficulties. Objectives To assess the effects of a memory rehabilitation program in patients with left temporal lobe epilepsy following surgery. Methods Twenty-four patients agreed to participate and 18 completed the study; nine received memory rehabilitation while nine had no input and were designated as controls. Verbal learning efficiency, naming abilities, memory subjective ratings, ecological activity measures and a language fMRI paradigm were used as outcome measures. Results Improved verbal learning and naming test performance, increase in memory strategy use and improved self-perception were observed following the rehabilitation. Changes in fMRI activation patterns were seen in the rehabilitation group over the long term. Conclusion The findings support the potential role of a cognitive rehabilitation program following left temporal lobe surgery.

The retail store managers' role: Evidence from Greece

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Zairis, A.

2013-03-01

Full Text Available Despite the fact that the retail manager's role is determinant for a store's performance, and there is abundant wisdom about how to be an outstanding manager or what are the characteristics of a successful retail manager, there is no detailed description about the store managers' role or their actual work. Furthermore, the continuous developments in the retail sector have established different roles and created higher levels of responsibility for store managers. The aim of the present paper is to empirically investigate the role of retail store managers in Greece and identify any potential differences in terms of personal characteristics, tasks and various job-related factors. For the purposes of this research a survey was conducted focusing on the sectors of apparel/footwear and food, in an attempt to explore any potential differences within the two divisions. The results revealed the profile of the Greek store managers (male, over the age of 40, with a secondary level of education and more than five years of work experience and their multi-factor role. The three major roles that they perform were labeled as: sales oriented, supervisor, and customer experience oriented. The research also indicated that the two most popular sub-sectors in the Greek retail industry employ different profile managers. The issues of work experience, job satisfaction and security were also analysed.

Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

Science.gov (United States)

Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

Science.gov (United States)

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

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Sheng-Chun Chiu

2014-09-01

Full Text Available Tanshinone IIA (Tan-IIA, one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

Potential role of a pharmacist to enhance medication-related aspects of clinical trials conducted in a dedicated clinical research unit

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Kimberly A. Redic, PharmD

2017-06-01

Conclusions: This pilot study showed potential roles for pharmacy personnel involvement in medication reconciliation in the clinical research setting. Pharmacists have the opportunity to ensure that IDs are accurately included in patient medication lists and to identify the use of potential protocol prohibited concomitant medications.

Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh

2016-01-01

is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose...... uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate...... kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed...

Long-Term Live Cell Imaging Reveals New Roles For Salmonella Effector Proteins SseG and SteA

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McQuate, Sarah E.; Young, Alexandra M.; Silva-Herzog, Eugenia; Bunker, Eric; Hernandez, Mateo; de Chaumont, Fabrice; Liu, Xuedong; Detweiler, Corrella S.; Palmer, Amy E.

2016-01-01

Summary Salmonella Typhimurium is an intracellular bacterial pathogen that infects both epithelial cells and macrophages. Salmonella effector proteins, which are translocated into the host cell and manipulate host cell components, control the ability to replicate and/or survive in host cells. Due to the complexity and heterogeneity of Salmonella infections, there is growing recognition of the need for single cell and live-cell imaging approaches to identify and characterize the diversity of cellular phenotypes and how they evolve over time. Here we establish a pipeline for long-term (16 hours) live-cell imaging of infected cells and subsequent image analysis methods. We apply this pipeline to track bacterial replication within the Salmonella-containing vacuole in epithelial cells, quantify vacuolar replication versus survival in macrophages, and investigate the role of individual effector proteins in mediating these parameters. This approach revealed that dispersed bacteria can coalesce at later stages of infection, that the effector protein SseG influences the propensity for cytosolic hyperreplication in epithelial cells, and that while SteA only has a subtle effect on vacuolar replication in epithelial cells, it has a profound impact on infection parameters in immunocompetent macrophages, suggesting differential roles for effector proteins in different infection models. PMID:27376507

Safeguards decision making in the public and regulatory environment, and the potential role of quantitative approaches

International Nuclear Information System (INIS)

Sherr, T.S.

1981-01-01

This paper briefly examines the nature of the safeguards program's objectives and constraints, and the inherent limitations on comprehensive quantification. It discusses the nature of the public and regulatory processes employed in safeguards decision making, and examines their implications regarding the potential role of quantitative approaches to safeguards policy and operational decision making

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

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Arzu Tatar

Full Text Available Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione and an oxidative product (malondialdehyde were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Development of the human potential in Russian and foreign countries

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Mikhail Ivanovich Maslennikov

2013-09-01

Full Text Available In the article, theoretical and methodical approaches to human development in Russia and foreign countries are analyzed. The contribution of the various countries to its formation and development is revealed. The indicators showing a level of development of human potential and components forming it in the creation of gross domestic product are analyzed. The alternative options of development of education, health care and science, expenses and benefit from their commercialization are revealed. The role of the state, federal regions and local authorities in management and development of health care, education, science during periods of crises, depressions and increases of economic activity is investigated. The interrelation of levels of development of the economy and human potential, with the levels and the population living conditions are revealed. The reasons of close attention of the governments of the developed countries to human development, and also the measures undertaken on minimization of interregional disproportions in its development become clear. Mechanisms and tools of development of health care, education, science in various regions of the world, a way of use of transfers, subsidies and grants on their development are investigated

Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of Keratinocyte

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Yunlu Gao

2017-01-01

Full Text Available RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs, pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.

Role of methylglyoxal as a transient receptor potential ankyrin 1 agonist in colon motility disturbances associated with diabetes

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Abdulmohsen Assiri

2017-01-01

Full Text Available Introduction: Evidence has been found to suggest that methylglyoxal (MG plays a mediating role in diabetes-related gastrointestinal conditions, and a possible mechanism relating to these conditions could be revealed by determining MG as a transient receptor potential ankyrin 1 (TRPA1 channel agonist. Methods: Muscle strips from the distal colon of male Wistar rats were used, and organ bath was employed to gain insight into the impact of MG + TRPA1 antagonist (HC-030031. Results: Considerable rise of spontaneous contractions for longitudinal muscle strips subjected to pre-treatment with MG were observed. The potentiation of the contractile response of control longitudinal muscle strips to electric field stimulation (EFS took place as a consequence of pre-treatment with 10 mM MG, and maximum response values displayed a rise from 2.16 g ± 0.323 to 3.64 g ± 0.421. 10 μM HC-030031 was observed to block the improvement of EFS responses by MG, and regarding circular muscle strips, a considerable decline in the maximum relaxation response was facilitated by 10 mM MG. Specifically, this was achieved at 20 Hz from 0.26 g ± 0.036 to 0.055 g ± 0.046. Conclusion: MG has been found to directly contract the distal colons of Wistar rats while enhancing the responses initiated as a result of carbachol and EFS. After blockading the impacts using HC-030031, evidence was found to suggest that the mediation of the impacts takes place through the activation of the TRPA1 channel, which occurs from the excretion of excitatory neurotransmitters. The findings also implicate MG in the blocking of inhibitory neurotransmission.

The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer.

Science.gov (United States)

Li, Xiaoduan; Wang, Xipeng

2017-05-15

Ovarian cancer (OC) is one of the three types of malignant tumors in the female reproductive system, and epithelial ovarian cancer (EOC) is its most typical form. Due to the asymptomatic nature of the early stages and resistance to chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current treatments for OC are very limited, and the 5-years survival rate is approximately 30%. Exosomes, which are microvesicles ranging from approximately 30-100 nm in size that are secreted by living cells, can be produced from different cell types and detected in various body fluids. Cancer cells can secrete more exosomes than healthy cells, and more importantly, the content of cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells are considered to be involved in tumor progression and metastasis. As such, exosomes are expected to be potential tools for tumor diagnosis and treatment. In this review, we briefly present the emerging roles of exosomes in OC and summarize related articles about their roles as diagnostic or prognostic biomarkers and in the treatment and drug resistance of OC.

The Role of the Transcriptional Response to DNA Replication Stress.

Science.gov (United States)

Herlihy, Anna E; de Bruin, Robertus A M

2017-03-02

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

The Role of the Transcriptional Response to DNA Replication Stress

Science.gov (United States)

Herlihy, Anna E.; de Bruin, Robertus A.M.

2017-01-01

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

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Dan Jiang

Full Text Available Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1 show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1, nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division.

THE ROLE OF THE INNOVATION POTENTIAL IN THE MANAGEMENT SYSTEM OF ECONOMIC SECURITY OF ENTERPRISES

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Y. P. Anisimov

2015-01-01

Full Text Available The article explores the theoretical foundations of innovative potential of the enterprise and its role for sustainable development and economic security. The urgency of the problem of sustainable development innovative capacity, low level of theoretical and practical elaboration, poor methodological and conceptual basis for the development of economic security, increasing competitiveness and strengthening market situation of enterprises, determined the choice of the research topic. Scientific awareness of the key problems of the economy determined the significance of the research topic, the relevance of which is determined by the need for new theoretical concepts, methodological developments and practical recommendations on the role of innovation potential in the management system of economic security of enterprises. The system of economic security management is the basis of the successful functioning and development of enterprises. In market conditions, the economic security of organizations is directly outside-the implementation of innovations into the production process, which is an effective means of increasing competitiveness, improving the quality of products. The innovative capacity of enterprises consists of a unique ability to increase such components as material and investment, information, personnel that will help the organization to achieve new strategic goals. It should be noted that not all products are offered by organizations on the existing market, generates potential, but only one that is potentially profitable. That is, the products created on the basis of innovative technologies, from-while a high quality and should demand amongst consumers. Economic security policy is a system of views, different measures, methods of solutions, specific actions in the area of economic security, which determine the conditions for achieving business goals. Thus, the implemented security policy allocates the organization to carry out economic

Immunonutrition: the role of taurine.

LENUS (Irish Health Repository)

Redmond, H P

2012-02-03

Taurine is a sulfonated beta amino acid derived from methionine and cysteine metabolism. It is present in high concentrations in most tissues and in particular in proinflammatory cells such as polymorphonuclear phagocytes. Initial investigation into the multifaceted properties of this non-toxic physiologic amino acid revealed a link between retinal dysfunction and dietary deficiency. Since then a role for this amino acid has been found in membrane stabilization, bile salt formation, antioxidation, calcium homeostasis, growth modulation, and osmoregulation. Our own group has demonstrated a key role for taurine in modulation of apoptosis in a variety of cell types. This review summarizes our current knowledge of taurine in nutrition, host proinflammatory cell homeostasis, therapeutic applications, and its potential immunoregulatory properties. It is our belief that taurine, similar to arginine and glutamine, is now more than worthy of critical clinical analysis.

An analysis of the potential role of chest tomosynthesis in optimising imaging resources in thoracic radiology

International Nuclear Information System (INIS)

Petersson, Cecilia; Baath, Magnus; Vikgren, Jenny; Allansdotter Johnsson, Aase

2016-01-01

The aim of the study was to investigate the potential role of chest tomosynthesis (CTS) at a tertiary referral centre by exploring to what extent CTS could substitute chest radiography (CXR) and computed tomography (CT). The study comprised 1433 CXR, 523 CT and 216 CTS examinations performed 5 years after the introduction of CTS. For each examination, it was decided if CTS would have been appropriate instead of CXR (CXR cases), if CTS could have replaced the performed CT (CT cases) or if CT would have been performed had CTS not been available (CTS cases). It was judged that (a) CTS had been appropriate in 15 % of the CXR examinations, (b) CTS could have replaced additionally 7 % of the CT examinations and (c) CT would have been carried out in 63 % of the performed CTS examinations, had CTS not been available. In conclusion, the potential role for CTS to substitute other modalities during office hours at a tertiary referral centre may be in the order of 20 and 25 % of performed CXR and chest CT, respectively. (authors)

AN ANALYSIS OF THE POTENTIAL ROLE OF CHEST TOMOSYNTHESIS IN OPTIMISING IMAGING RESOURCES IN THORACIC RADIOLOGY

Science.gov (United States)

Petersson, Cecilia; Båth, Magnus; Vikgren, Jenny; Johnsson, Åse Allansdotter

2016-01-01

The aim of the study was to investigate the potential role of chest tomosynthesis (CTS) at a tertiary referral centre by exploring to what extent CTS could substitute chest radiography (CXR) and computed tomography (CT). The study comprised 1433 CXR, 523 CT and 216 CTS examinations performed 5 years after the introduction of CTS. For each examination, it was decided if CTS would have been appropriate instead of CXR (CXR cases), if CTS could have replaced the performed CT (CT cases) or if CT would have been performed had CTS not been available (CTS cases). It was judged that (a) CTS had been appropriate in 15 % of the CXR examinations, (b) CTS could have replaced additionally 7 % of the CT examinations and (c) CT would have been carried out in 63 % of the performed CTS examinations, had CTS not been available. In conclusion, the potential role for CTS to substitute other modalities during office hours at a tertiary referral centre may be in the order of 20 and 25 % of performed CXR and chest CT, respectively. PMID:26979807

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

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Faure Claudine

2007-10-01

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

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

NK cell recruitment and exercise: Potential immunotherapeutic role of shear stress and endothelial health.

Science.gov (United States)

Evans, William

2017-11-01

Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium. Additionally, shear stress may play a role in improving NK cell function by decreasing oxidative stress. The relationship between shear stress and NK cell count and function can be tested by utilizing exercise and local heating with cuff inflation. If shear stress does play an important role, NK cell count and function will be improved in the non-cuffed exercise group, but not the cuffed limb. This paper will explore the mechanisms potentially explaining exercise-induced improvements in NK cell count and function, and propose a model for investigating these mechanisms. This mechanistic insight could aid in providing a novel, safe, relatively inexpensive, and non-invasive target for immunotherapy in cancer patients. Copyright © 2017. Published by Elsevier Ltd.

Liberating the potential: the role of non-nurses in adding value to nurse education.

Science.gov (United States)

Dickinson, Julie

2006-01-01

In this paper, I have attempted to explore the role of non-nurse lecturers in adding value to nurse education programmes. In measuring "added-value" in higher education, I have embraced a more comprehensive approach including investigating the views of "Experts"; including the nurse and non-nurse lecturers themselves, and various United Kingdom stakeholders such as the Government, the Nursing and Midwifery Council and the Quality Assurance Agency. The students' views are also taken into account, when considering both the content of the programmes and how they are delivered. The complexity of "objective measurement" is considered, and the requirements of a "good" teaching experience. The potential areas for adding value include: health and social care policy priorities which encourage partnership working, the blurring of professional boundaries, and inter-professional working. Professional-specific changes embracing extended and enhanced roles and the concepts of specialist and assistant practitioners. Other areas include the Higher Education agendas including transferable skills and adult and student-centred learning. I conclude by discussing the latest policy changes and suggest that the role of the non-nurse lecturer needs more exploration to provide the best value for all.

Revealing Fundamental Interactions: the Role of Polarized Positrons and Electrons at the Linear Collider

International Nuclear Information System (INIS)

Moortgat-Pick, G.; CERN, Durham U. IPPP; Abe, T.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke, J.; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, T.; Eberl, H.; Ellis, John R.; Flottman, K.; Frass, H.

2005-01-01

The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization

Revealing Fundamental Interactions: the Role of Polarized Positrons and Electrons at the Linear Collider

Energy Technology Data Exchange (ETDEWEB)

Moortgat-Pick, G.; /CERN /Durham U., IPPP; Abe, T.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke,; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, T.; Eberl, H.; Ellis, John R.; Flottman, K.; Frass, H.; /CERN /Durham U., IPPP /Colorado U. /Tel-Aviv

2005-07-06

The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.

Comprehensive RNA Polymerase II Interactomes Reveal Distinct and Varied Roles for Each Phospho-CTD Residue

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Kevin M. Harlen

2016-06-01

Full Text Available Transcription controls splicing and other gene regulatory processes, yet mechanisms remain obscure due to our fragmented knowledge of the molecular connections between the dynamically phosphorylated RNA polymerase II (Pol II C-terminal domain (CTD and regulatory factors. By systematically isolating phosphorylation states of the CTD heptapeptide repeat (Y1S2P3T4S5P6S7, we identify hundreds of protein factors that are differentially enriched, revealing unappreciated connections between the Pol II CTD and co-transcriptional processes. These data uncover a role for threonine-4 in 3′ end processing through control of the transition between cleavage and termination. Furthermore, serine-5 phosphorylation seeds spliceosomal assembly immediately downstream of 3′ splice sites through a direct interaction with spliceosomal subcomplex U1. Strikingly, threonine-4 phosphorylation also impacts splicing by serving as a mark of co-transcriptional spliceosome release and ensuring efficient post-transcriptional splicing genome-wide. Thus, comprehensive Pol II interactomes identify the complex and functional connections between transcription machinery and other gene regulatory complexes.

Beyond gender stereotypes in language comprehension: self sex-role descriptions affect the brain's potentials associated with agreement processing

OpenAIRE

Paolo eCanal; Paolo eCanal; Alan eGarnham; Jane eOakhill

2015-01-01

We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as king or engineer) or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a P60...

On the Potential Role of Species Separation in DT Fuels on Implosion Performance

Science.gov (United States)

Amendt, Peter; Bellei, Claudio; Wilks, Scott; Haines, Malcolm; Casey, Dan; Li, C. K.; Petrasso, Richard

2012-10-01

The measurement of strong, self-generated electric fields (1-10 GVolts/m) in imploding capsules [1], their attribution to polarized (plasma) shock fronts [2], and the identification of plasma-enhanced binary species diffusion from barodiffusion and electrodiffusion [3] have led to a growing interest in the potential role of species separation in inertial-confinement-fusion (ICF) thermonuclear fuels. The potential for anomalous heating from transient frictional or resistive drag between D and T across a finite thickness shock front will be assessed and applied towards ignition thresholds and understanding some outstanding anomalies in the Omega implosion database.[4pt] [1] J.R. Rygg et al., Science 319, 1223 (2008); C.K. Li et al., Phys. Rev. Lett. 100, 225001 (2008).[0pt] [2] P.A. Amendt, J.L. Milovich, S.C. Wilks, C.K. Li, R.D. Petrasso and F.H. S'eguin, Plasma Phys. Control. Fusion 51, 124048 (2009).[0pt] [3] P. Amendt, C. Bellei and S.C. Wilks, Phys. Rev. Lett. (to appear).

The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease.

Science.gov (United States)

Amaral, Marta; Outeiro, Tiago F; Scrutton, Nigel S; Giorgini, Flaviano

2013-06-01

Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds.

Estimation of Polar Cap Potential and the Role of PC Index

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Ga-Hee Moon

2012-09-01

Full Text Available Polar cap potential has long been considered as an indicator for the amount of energy flowing in the magnetosphere-ionosphere system. Thus, the estimation of polar cap potential is important to understand the physical process of the magnetosphere. To estimate the polar cap potential in the Northern Hemisphere, merging electric field by Kan & Lee (1979 is adopted. Relationships between the PC index and calculated merging electric field (E* are examined during full-time and storm-time periods separately. For this purpose Dst, AL, and PC indices and solar wind data are utilized during the period from 1996-2003. From this linear relationship, polar cap potential (Φ* is estimated using the formula by Doyle & Burke (1983. The values are represented as 58.1 ± 26.9 kV for the full-time period and 123.7 ± 84.1 kV for a storm-time period separately. Considering that the average value of polar cap potential of Doyle & Burke (1983 is about 47 kV during moderately quiet intervals with the S3-2 measurements, these results are similar to such. The monthly averaged variation of Dst, AL, and PC indices are then compared. The Dst and AL indices show distinct characteristics with peaks during equinoctial season whereas the average PC index according to the month shows higher values in autumn than in spring. The monthly variations of the linear correlation coefficients between solar wind parameters and geomagnetic indices are also examined. The PC-AL linear correlation coefficient is highest, being 0.82 with peaks during the equinoctial season. As with the AL index, the PC index may also prove useful for predicting the intensity of an auroral substorm. Generally, the linear correlation coefficients are shown low in summer due to conductance differences and other factors. To assess the role of the PC index during the recovery phase of a storm, the relation between the cumulative PC index and the duration is examined. Although the correlation coefficient lowers

Introduction to the role of the immune system in melanoma.

Science.gov (United States)

Margolin, Kim

2014-06-01

The concept of immunosurveillance of cancer has been widely accepted for many years, but only recently have the precise mechanisms of tumor-host immune interactions been revealed. Inflammatory and immune reactions play a role in melanomagenesis, and may contribute to the eradication of tumor as well as potentiating its growth and proliferation. Studies of the role of tumor-immune system interactions are providing insights into the pathogenesis and opportunities for highly effective therapeutic strategies. Some patients, even with advanced disease, are now cured with immunotherapy, and increasing numbers of such cures are likely in future. Copyright © 2014 Elsevier Inc. All rights reserved.

Management simulations for Lean healthcare: exploiting the potentials of role-playing.

Science.gov (United States)

Barnabè, Federico; Giorgino, Maria Cleofe; Guercini, Jacopo; Bianciardi, Caterina; Mezzatesta, Vincenzo

2018-04-09

Purpose The purpose of this paper is to investigate the potentials of role-playing (RP) both in training healthcare (HC) professionals to implement tools and improvement actions based on Lean principles, and in supporting group discussion and the sharing of different competencies for the development of Lean HC. Design/methodology/approach The paper presents the case study of an RP simulation called LEAN HEALTHCARE LAB, which is used to train HC professionals at Siena University Hospital. The paper reports and discusses the results of a specific two-day simulation session and of a questionnaire that was distributed to gather feedback from the participants. Findings The paper verifies the potentials of RP to be a powerful educational and training tool that is able to stimulate the HC participants to apply Lean thinking principles and share their competencies in collaborative decision-making processes. Research limitations/implications The study provides data in reference to one single simulation session, although the game has already been applied several times in different HC organizations with very similar outcomes. Moreover, a more in-depth analysis of players' perceptions and decisions could be performed using different tools in addition to the adopted questionnaire. Practical implications RP games (RPGs) are effective training and educational tools for HC professionals. They offer benefits and learning conditions which are definitely different if compared with more conventional education programs for HC professionals. Originality/value While previous studies have extensively discussed the potentialities of RPG and simulations in training programs, only a few articles have discussed the RP adoption for Lean thinking and even less to educate HC professionals on Lean principles and tools.

The potential role of stethoscopes as a source of nosocomial infection

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Neetu Gupta

2014-01-01

Full Text Available Background: Infectious diseases can be transmitted in various ways . Indirect transmission or vehicle-borne transmission of infection can occur through various agents like instruments, utensils, water, or food. In hospital settings, transmission of infection through contaminated medical devices is always a possibility. Stethoscope is the symbol of health professionals. However, the diaphragm and bells of the stethoscopes have been shown to harbor pathogenic and nonpathogenic microorganisms. Aims: 1 To determine the degree of contamination of stethoscopes used by clinicians and nurses. 2 To identify various microbes from such contaminated stethoscopes and to assess their role as potential pathogens. 3 To determine the effectiveness of 70% ethanol as a disinfecting agent. Materials and Methods: Stethoscopes of 50 healthcare workers from different departments were included in the study. Bacteriological cultures of the samples were done on blood agar and MacConkey agar plates. Organisms were identified by conventional phenotypic methods. Antibiotic sensitivity test (ABST of the microorganisms was performed by Kirby-Bauer disk diffusion method. Results: Average number of colonies on each stethoscope was 30 . Pathogenic microorganisms including Staphylococcus aureus, Acinetobacter species, Citrobacter species, Pseudomonas stutzeri, Bacillus species, and Aspergillus fumigatus were identified. Among the potential pathogenic organisms, coagulase-negative staphylococci were isolated. Numbers of colonies were highest among the stethoscopes sampled from surgery ward and Medical Intensive Care Unit MICU. Conclusion: Stethoscopes harbor potential pathogens capable of surviving on their surfaces. Despite their best intentions, health professionals can act as a vector for transmission of disease. Disinfecting procedures may be necessary between consecutive patients. Attention to simple preventive strategies can reduce the disease transmission rate.

Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer

International Nuclear Information System (INIS)

Kim, Dong Wook; Choy, Hak

2004-01-01

There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy ± surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Science.gov (United States)

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

2003-01-01

Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P＜0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

Comparative assessment of different energy sources and their potential role in long-term sustainable energy mix

International Nuclear Information System (INIS)

Kagramanian, V.S.

2001-01-01

In the debate on sustainable energy future, the role of nuclear power is a contentious issue. Many, who are outside of the nuclear community, do not even consider nuclear, because of public concerns on nuclear safety, radioactive waste and non-proliferation issues. For example, the United Nations Development Program, in its document Energy After Rio does not suggest a specific role for nuclear power except in the most doubtful of terms. On the contrary, most nuclear organisations and related industries see nuclear power as the only mature carbon-free electricity generating option that can be deployed even on a much larger scale than today. This paper analyses the potential role of nuclear power in the context of the global sustainable energy future. The fundamental features of sustainable energy development are examined in terms of the following compatibility constraints: Demand driven compatibility; Natural resource compatibility; Environmental compatibility; Geopolitical compatibility; and Economic compatibility

The potential role of omega-3 fatty acids supplements in increasing athletic performance

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Șerban GLIGOR

2017-03-01

Full Text Available Polyunsaturated omega-3 and omega-6 fatty acids are essential fatty acids that cannot be produced by the body itself and therefore must be provided through nutrition. Omega-6 and particularly omega-3 fatty acids have important roles in the organism, contributing to the maintenance and promotion of health. The optimal proportion of omega-6/omega-3 fatty acids is 2:1, or even better 1:1. They are involved in normal growth and development, play a role in the prevention of coronary and cardiovascular diseases, of diabetes mellitus, of arterial hypertension, arthritis and cancer. Omega-3 fatty acids mainly have an anti-inflammatory effect, but also act as hypolipidemic and antithrombotic agents. A potential role of omega-3 fatty acids is that of increasing physical performance. Their role in the physical activity refers on one side to the global health of athletes and on the other side to their anti-inflammatory effect, as high intensity physical exercise induces increased free-radical production and microtraumas, with the induction of an inflammatory status. The anti-inflammatory effect of these fatty acids manifests through an increased production of endogenous antioxidant enzymes, through decreasing the production of prostaglandins metabolites, decreasing the production of leukotriene B4, etc. They are also effective on reducing muscle pain post eccentric exercise and on decreasing the severity of bronchoconstriction induced by exercise, as well as improving pulmonary function variables. In conclusion it seems that supplementing diets with omega-3 fatty acids, apart from having benefic effects on health and on the prevention and management of certain affections, proves to be a beneficial for physical activity and athletic performance.

Hostage (crisis) negotiation: the potential role of negotiator personality, decision-making style, coping style and emotional intelligence on negotiator success.

Science.gov (United States)

Grubb, Amy; Brown, Sarah

2012-01-01

This article explores the potential role of hostage negotiator characteristics and the impact of psychological constructs on negotiator success. It explores the role of Personality, Decision-Making Style, Coping Style, Cognitive Coping Style and Emotion Regulation and Emotional Intelligence within high stress environments and occupations. The findings suggest that certain individual traits and characteristics may play a role in negotiator success, via the mediation of specific styles, which are conducive to effective crisis negotiation skills. It is proposed that these findings have application within the field of hostage/crisis negotiation in the format of guidance regarding the recruitment and selection of hostage negotiators and the identification of potential training needs within individual negotiators in order to maximize their efficacy within the field. In line with this, it is argued that a psychometric tool that assesses these constructs is developed in order to aid the process of hostage negotiation selection.

The link between otitis media with effusion and allergy: a potential role for intranasal corticosteroids.

Science.gov (United States)

Lack, Gideon; Caulfield, Helen; Penagos, Martin

2011-05-01

We reviewed the evidence linking otitis media with effusion (OME) and atopy, with the goal of clarifying the possible role of intranasal corticosteroids (INSs) in OME treatment. In August 2009, the MEDLINE database was searched for primary studies on OME epidemiology, pathophysiology, and treatment. Relevant clinical guidelines were obtained. Interpreting OME research is complicated by variable disease definitions, patient populations, methodologies, and outcomes assessments, along with the possibility of spontaneous resolution. However, evidence links OME with atopic conditions including allergic rhinitis; observed prevalence of allergic rhinitis in patients with chronic or recurrent OME ranges from 24% to 89%. Such findings have prompted evaluations of common allergy medications for OME treatment. While short-term use of INSs alone or combined with antibiotics has shown benefit in some studies, more prolonged treatment protocols and long-term clinical outcomes will require critical assessment. Evidence suggesting epidemiologic and pathophysiologic links between allergy and OME has prompted investigation into a potential role for INSs in OME management, with promising initial results. Benefits of considering medical treatment in patients with OME prior to surgery include both the potential reductions in allergic inflammation and the naturally occurring spontaneous resolution of OME in these patients. © 2011 John Wiley & Sons A/S.

Characterization of the sebocyte lipid droplet proteome reveals novel potential regulators of sebaceous lipogenesis.

Science.gov (United States)

Dahlhoff, Maik; Fröhlich, Thomas; Arnold, Georg J; Müller, Udo; Leonhardt, Heinrich; Zouboulis, Christos C; Schneider, Marlon R

2015-03-01

Lipid metabolism depends on lipid droplets (LD), cytoplasmic structures surrounded by a protein-rich phospholipid monolayer. Although lipid synthesis is the hallmark of sebaceous gland cell differentiation, the LD-associated proteins of sebocytes have not been evaluated systematically. The LD fraction of SZ95 sebocytes was collected by density gradient centrifugation and associated proteins were analyzed by nanoliquid chromatography/tandem mass spectrometry. 54 proteins were significantly enriched in LD fractions, and 6 of them have not been detected previously in LDs. LD fractions contained high levels of typical LD-associated proteins as PLIN2/PLIN3, and most proteins belonged to functional categories characteristic for LD-associated proteins, indicating a reliable dataset. After confirming expression of transcripts encoding the six previously unidentified proteins by qRT-PCR in SZ95 sebocytes and in another sebocyte line (SebE6E7), we focused on two of these proteins, ALDH1A3 and EPHX4. While EPHX4 was localized almost exclusively on the surface of LDs, ALDH1A3 showed a more widespread localization that included additional cytoplasmic structures. siRNA-mediated downregulation revealed that depletion of EPHX4 increases LD size and sebaceous lipogenesis. Further studies on the roles of these proteins in sebocyte physiology and sebaceous lipogenesis may indicate novel strategies for the therapy of sebaceous gland-associated diseases such as acne. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of depth and location of minima of a double-well potential on vibrational resonance

International Nuclear Information System (INIS)

Rajasekar, S; Jeyakumari, S; Chinnathambi, V; Sanjuan, M A F

2010-01-01

We report our investigation into the role of depth and location of minima of a double-well potential on vibrational resonance in both underdamped and overdamped Duffing oscillators. The systems are driven by both low- and high-frequency periodic forces. We obtain theoretical expressions for the amplitude g of the high-frequency force at which resonances occur. The depth and location of the minima of the potential wells have a distinct effect on vibrational resonance in the underdamped and overdamped cases. In the underdamped system at least one resonance and at most two resonances occur and the number of resonances can be altered by varying the depth and location of the minima of the potential wells. We show that in the overdamped system there is always one and only one resonance, and the value of g at which resonance occurs is independent of the depth of the wells, but varies linearly with the locations of the minima of the wells.

Socio-motivational moderators—two sides of the same coin? Testing the potential buffering role of socio-motivational relationships on achievement drive and test anxiety among German and Canadian secondary school students

Science.gov (United States)

Hoferichter, Frances; Raufelder, Diana; Eid, Michael

2015-01-01

The current cross-national study investigates the potential buffering role of socio-motivational relationships for the association of achievement drive (AD) and test anxiety (TX) in secondary school students from Canada and Germany. One thousand and eighty-eight students (54% girls, Mage = 13.71, SD = 0.53, age span 12–15 years) from the state of Brandenburg and 389 students from Quebéc (55.9% girls, Mage = 13.43, SD = 0.82, age span 12–16 years) were asked about their socio-motivational relationships with their teachers and peers, their drive for achievement, and TX. Multigroup latent moderated structural equations were conducted to test for the moderator role of socio-motivational relationships that would buffer feelings of TX related to the drive for achievement. The analyses revealed the two-sided role socio-motivational relationships can have for students with different levels of AD; intensifying or mitigating feelings of TX. Thereby, the results of this study extend the buffering hypothesis by Cohen and Wills (1985). Cross-national differences between Canada and Germany were found concerning the studied moderators on the association of AD and TX: While for German students teacher–student relationships acted as moderator, for Canadian students student–student relationships and teachers acting as positive motivators displayed a moderator role. PMID:26583000

Socio-motivational moderators-two sides of the same coin? Testing the potential buffering role of socio-motivational relationships on achievement drive and test anxiety among German and Canadian secondary school students.

Science.gov (United States)

Hoferichter, Frances; Raufelder, Diana; Eid, Michael

2015-01-01

The current cross-national study investigates the potential buffering role of socio-motivational relationships for the association of achievement drive (AD) and test anxiety (TX) in secondary school students from Canada and Germany. One thousand and eighty-eight students (54% girls, M age = 13.71, SD = 0.53, age span 12-15 years) from the state of Brandenburg and 389 students from Quebéc (55.9% girls, M age = 13.43, SD = 0.82, age span 12-16 years) were asked about their socio-motivational relationships with their teachers and peers, their drive for achievement, and TX. Multigroup latent moderated structural equations were conducted to test for the moderator role of socio-motivational relationships that would buffer feelings of TX related to the drive for achievement. The analyses revealed the two-sided role socio-motivational relationships can have for students with different levels of AD; intensifying or mitigating feelings of TX. Thereby, the results of this study extend the buffering hypothesis by Cohen and Wills (1985). Cross-national differences between Canada and Germany were found concerning the studied moderators on the association of AD and TX: While for German students teacher-student relationships acted as moderator, for Canadian students student-student relationships and teachers acting as positive motivators displayed a moderator role.

Epigenetic Alterations in Fanconi Anaemia: Role in Pathophysiology and Therapeutic Potential.

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Hélio Belo

Full Text Available Fanconi anaemia (FA is an inherited disorder characterized by chromosomal instability. The phenotype is variable, which raises the possibility that it may be affected by other factors, such as epigenetic modifications. These play an important role in oncogenesis and may be pharmacologically manipulated. Our aim was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. We compared expression of epigenetic genes and DNA methylation profile of tumour suppressor genes between FA and normal samples. FA samples exhibited decreased expression levels of genes involved in epigenetic regulation and hypomethylation in the promoter regions of tumour suppressor genes. Treatment of FA cells with histone deacetylase inhibitor Vorinostat increased the expression of DNM3Tβ and reduced the levels of CIITA and HDAC9, PAK1, USP16, all involved in different aspects of epigenetic and immune regulation. Given the ability of Vorinostat to modulate epigenetic genes in FA patients, we investigated its functional effects on the FA phenotype. This was assessed by incubating FA cells with Vorinostat and quantifying chromosomal breaks induced by DNA cross-linking agents. Treatment of FA cells with Vorinostat resulted in a significant reduction of aberrant cells (81% on average. Our results suggest that epigenetic mechanisms may play a role in oncogenesis in FA. Epigenetic agents may be helpful in improving the phenotype of FA patients, potentially reducing tumour incidence in this population.

Nuclear power in developing countries: Its potential role and strategies for its deployment. Proceedings

International Nuclear Information System (INIS)

2000-01-01

The demand for energy, especially electricity, in developing countries is expected to grow rapidly in the coming decades as these countries seek to improve the living standards of their growing populations. Substantial growth in developing country energy demand plus a continued heavy reliance of the power sector on fossil fuels is likely to result in an increased dependence of these countries on energy imports and thus to potential deterioration of their terms-of-trade, reduced energy security and, in the absence of costly mitigation measures, severe degradation of the environment and public health, and will also lead to increasing emissions of greenhouse gases. If supply security, health and environmental protection and climate change become pressing policy issues, nuclear power is, in the short to medium term, the only viable non-fossil base load electricity generating alternative (other than hydro where growth potential is limited) that is already meeting 17% of global electricity needs and contributing more than 30% of electricity supplies in 14 countries. It is in the above context that the International Atomic Energy Agency organized this seminar to explore the role of nuclear power in meeting the growing demand for electricity in the developing world, and to identify and discuss suitable ways and means for proper implementation of nuclear power programmes in these countries. Several issues were discussed, in particular, the need and role of nuclear power; economic and financial aspects; technology transfer and national participation; safety, regulation and safeguards; and public acceptance

Nuclear power in developing countries: Its potential role and strategies for its deployment. Proceedings

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-08-01

The demand for energy, especially electricity, in developing countries is expected to grow rapidly in the coming decades as these countries seek to improve the living standards of their growing populations. Substantial growth in developing country energy demand plus a continued heavy reliance of the power sector on fossil fuels is likely to result in an increased dependence of these countries on energy imports and thus to potential deterioration of their terms-of-trade, reduced energy security and, in the absence of costly mitigation measures, severe degradation of the environment and public health, and will also lead to increasing emissions of greenhouse gases. If supply security, health and environmental protection and climate change become pressing policy issues, nuclear power is, in the short to medium term, the only viable non-fossil base load electricity generating alternative (other than hydro where growth potential is limited) that is already meeting 17% of global electricity needs and contributing more than 30% of electricity supplies in 14 countries. It is in the above context that the International Atomic Energy Agency organized this seminar to explore the role of nuclear power in meeting the growing demand for electricity in the developing world, and to identify and discuss suitable ways and means for proper implementation of nuclear power programmes in these countries. Several issues were discussed, in particular, the need and role of nuclear power; economic and financial aspects; technology transfer and national participation; safety, regulation and safeguards; and public acceptance.

Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.

Directory of Open Access Journals (Sweden)

Xiao-Xiao Qin

2018-04-01

Full Text Available The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce (Lactuca sativa L. cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole–Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.).

Science.gov (United States)

Qin, Xiao-Xiao; Zhang, Ming-Yue; Han, Ying-Yan; Hao, Jing-Hong; Liu, Chao-Jie; Fan, Shuang-Xi

2018-04-11

The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce ( Lactuca sativa L.) cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

Roles of protein kinase R in cancer: Potential as a therapeutic target.

Science.gov (United States)

Watanabe, Takao; Imamura, Takeshi; Hiasa, Yoichi

2018-04-01

Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune antiviral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor as a result of its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant disease, such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus (HCV) is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In the present review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The development of psychotic disorders in adolescence: a potential role for hormones.

Science.gov (United States)

Trotman, Hanan D; Holtzman, Carrie W; Ryan, Arthur T; Shapiro, Daniel I; MacDonald, Allison N; Goulding, Sandra M; Brasfield, Joy L; Walker, Elaine F

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Deployed communication between the Role 3 and Role 1.

Science.gov (United States)

Parsons, Iain T

2015-06-01

The discharge summary is the most common method for documenting a patient's diagnostic findings, hospital management and arrangements for post-discharge follow up. After being discharged from hospital, patients are routinely reviewed without a discharge summary being available. A recent review revealed that a significant proportion of patients discharged from the Role 3 had no evidence of their admission on their permanent medical record. The aim of this audit was to assess the transition of discharge summaries from Role 3 to Role 1 during Op HERRICK 18. The intention was to review where errors in the transfer of discharge information between Role 3 and Role 1 might be occurring with a view to implementing improvements. Two audits assessed the delivery of discharge information. A re-audit was performed 1 month after a system was implemented. The transfer of discharge information was poor with only 1/40 (2.5%) summaries arriving from R3 to R1. Following implementation of a system the transfer of discharge information improved to 24/30 (80%). The adoption of a system to transit discharge information from R3 to R1 resulted in a drastic improvement. Ideally, a future electronic patient record system used by all facets of Defence Medical Services would limit the potential for future adverse events due to communication failure. Regular audits assessing the transfer of discharge information should form part of standard audit cycles in future contingency operations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

AN ANALYSIS OF THE POTENTIAL ROLE OF CHEST TOMOSYNTHESIS IN OPTIMISING IMAGING RESOURCES IN THORACIC RADIOLOGY.

Science.gov (United States)

Petersson, Cecilia; Båth, Magnus; Vikgren, Jenny; Johnsson, Åse Allansdotter

2016-06-01

The aim of the study was to investigate the potential role of chest tomosynthesis (CTS) at a tertiary referral centre by exploring to what extent CTS could substitute chest radiography (CXR) and computed tomography (CT). The study comprised 1433 CXR, 523 CT and 216 CTS examinations performed 5 years after the introduction of CTS. For each examination, it was decided if CTS would have been appropriate instead of CXR (CXR cases), if CTS could have replaced the performed CT (CT cases) or if CT would have been performed had CTS not been available (CTS cases). It was judged that (a) CTS had been appropriate in 15 % of the CXR examinations, (b) CTS could have replaced additionally 7 % of the CT examinations and (c) CT would have been carried out in 63 % of the performed CTS examinations, had CTS not been available. In conclusion, the potential role for CTS to substitute other modalities during office hours at a tertiary referral centre may be in the order of 20 and 25 % of performed CXR and chest CT, respectively. © The Author 2016. Published by Oxford University Press.

A short overview of the microbial population in clouds: Potential roles in atmospheric chemistry and nucleation processes

Science.gov (United States)

Delort, Anne-Marie; Vaïtilingom, Mickael; Amato, Pierre; Sancelme, Martine; Parazols, Marius; Mailhot, Gilles; Laj, Paolo; Deguillaume, Laurent

2010-11-01

Recent studies showed that living microorganisms, including bacteria, fungi and yeasts, are present in the atmospheric water phase (fog and clouds) and their role in chemical processes may have been underestimated. At the interface between atmospheric science and microbiology, information about this field of science suffers from the fact that not all recent findings are efficiently conveyed to both scientific communities. The purpose of this paper is therefore to provide a short overview of recent work linked to living organisms in the atmospheric water phase, from their activation to cloud droplets and ice crystal, to their potential impact on atmospheric chemical processes. This paper is focused on the microorganisms present in clouds and on the role they could play in atmospheric chemistry and nucleation processes. First, the life cycle of microorganisms via the atmosphere is examined, including their aerosolization from sources, their integration into clouds and their wet deposition on the ground. Second, special attention is paid to the possible impacts of microorganisms on liquid and ice nucleation processes. Third, a short description of the microorganisms that have been found in clouds and their variability in numbers and diversity is presented, emphasizing some specific characteristics that could favour their occurrence in cloud droplets. In the last section, the potential role of microbial activity as an alternative route to photochemical reaction pathways in cloud chemistry is discussed.

Genome and metagenome enabled analyses reveal new insight into the global biogeography and potential urea utilization in marine Thaumarchaeota.

Science.gov (United States)

Ahlgren, N.; Parada, A. E.; Fuhrman, J. A.

2016-02-01

Marine Thaumarchaea are an abundant, important group of marine microbial communities as they fix carbon, oxidize ammonium, and thus contribute to key N and C cycles in the oceans. From an enrichment culture, we have sequenced the complete genome of a new Thaumarchaeota strain, SPOT01. Analysis of this genome and other Thaumarchaeal genomes contributes new insight into its role in N cycling and clarifies the broader biogeography of marine Thaumarchaeal genera. Phylogenomics of Thaumarchaeota genomes reveal coherent separation into clusters roughly equivalent to the genus level, and SPOT01 represents a new genus of marine Thaumarchaea. Competitive fragment recruitment of globally distributed metagenomes from TARA, Ocean Sampling Day, and those generated from a station off California shows that the SPOT01 genus is often the most abundant genus, especially where total Thaumarchaea are most abundant in the overall community. The SPOT01 genome contains urease genes allowing it to use an alternative form of N. Genomic and metagenomic analysis also reveal that among planktonic genomes and populations, the urease genes in general are more frequently found in members of the SPOT01 genus and another genus dominant in deep waters, thus we predict these two genera contribute most significantly to urea utilization among marine Thaumarchaea. Recruitment also revealed broader biogeographic and ecological patterns of the putative genera. The SPOT01 genus was most abundant at colder temperatures (45 degrees). The genus containing Nitrosopumilus maritimus had the highest temperature range, and the genus containing Candidatus Nitrosopelagicus brevis was typically most abundant at intermediate temperatures and intermediate latitudes ( 35-45 degrees). Together these genome and metagenome enabled analyses provide significant new insight into the ecology and biogeochemical contributions of marine archaea.

The Arabidopsis nox mutant lacking carotene hydroxylase activity reveals a critical role for xanthophylls in photosystem I biogenesis.

Science.gov (United States)

Dall'Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

2013-02-01

Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth.

Embedding the assistant practitioner role within the clinical department: A qualitative study

International Nuclear Information System (INIS)

Bennion, Colette M.; Irvine, Fiona

2011-01-01

Aim: To evaluate the Assistant Practitioner (AP) role in terms of service delivery and gain insight into the improvements that could be made in embedding this role effectively. This evaluation was timely as the role had been established in radiography for several years and there was limited research which explored its success in practice. Method: A qualitative approach was used to examine the perceptions of radiology managers using a regional focus group (n = 10) and follow up interviews (n = 4). These were designed to gain an understanding of the managers' views. Focus groups and interviews were audio recorded and transcribed. Data were analysed using a framework analysis approach to reveal salient issues. Results: Three main themes representing the perceptions of the role were uncovered and these related to organisational issues, the educational perspective and the individual perspective. This paper is restricted to in depth reporting and analyses of the organisational and individual perspectives only. Analysis revealed several factors facilitated the role in practice but equally other factors inhibited its effectiveness. Conclusions: There is potential for the AP role to support the work of radiographers and more importantly enhance the care of patients. However, certain individual views should be addressed and the identified changes in departmental organisation attended to, if the role is to develop successfully and become firmly embedded in the radiography service structure.

Role of L-Type Ca[superscript 2+] Channel Isoforms in the Extinction of Conditioned Fear

Science.gov (United States)

Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J.; Striessnig, Jorg; Singewald, Nicolas

2008-01-01

Dihydropyridine (DHP) L-type Ca[superscript 2+] channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the…

Review: MicroRNAs in assisted reproduction and their potential role in IVF failure.

Science.gov (United States)

Siristatidis, Charalampos; Vogiatzi, Paraskevi; Brachnis, Nikos; Liassidou, Aspasia; Iliodromiti, Zoe; Bettocchi, Stefano; Chrelias, Charalampos

2015-01-01

MicroRNAs (miRNAs) have recently emerged as important regulators of gene expression stability. In the endometrium, miRNAs are involved in the dynamic changes associated with the menstrual cycle, implicated in implantation and in reproductive disorders. We performed a review in an attempt to assess the potential biological pathways linking altered miRNAs profiles with in vitro fertilisation (IVF) failure. Crucially, as miRNAs appear to have a significant role in the course of reproduction, they are excellent research candidates with the potential to enable a better understanding over the underlying molecular activities that prevent implantation and further progression of the embryo. Further steps include in-depth pathway mapping of the implantation process and the characterization of the respective miRNAs and associated links. The efficiency of any intervention should determine whether miRNA profiling could possibly be adopted in routine practice to substantially improve the diagnostic accuracy and, in parallel, the directed treatment of the next-generation IVF. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

International Nuclear Information System (INIS)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao

2013-01-01

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

Energy Technology Data Exchange (ETDEWEB)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin, E-mail: jqin710@vip.sina.com; Yan, Biao, E-mail: yanbiao1982@hotmail.com

2013-09-06

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.

Beyond Gender Stereotypes in Language Comprehension: Self Sex-Role Descriptions Affect the Brain’s Potentials Associated with Agreement Processing

OpenAIRE

Canal, Paolo; Garnham, Alan; Oakhill, Jane

2015-01-01

We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as “king” or “engineer”) or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a...

The role of CDX2 in intestinal homeostasis and inflammation

DEFF Research Database (Denmark)

Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

2011-01-01

a causal role in a large number of diseases and developmental disorders. Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa caused by dysregulation of the intestinal immune homeostasis. The aetiology of IBD is thought to be a combination of genetic and environmental factors......, including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...... of the intestinal homeostasis and further to reveal its potential role in inflammation....

Infinite potential: what quantum physics reveals about how we should live

CERN Document Server

Schafer, Lothar

2013-01-01

A hopeful and controversial view of the universe and ourselves based on the principles of quantum physics, offering a way of making our lives and the world better, with a foreword by Deepak Chopra     In Infinite Potential, physical chemist Lothar Schäfer presents a stunning view of the universe as interconnected, nonmaterial, composed of a field of infinite potential, and conscious. With his own research as well as that of some of the most distinguished scientists of our time, Schäfer moves us from a reality of Darwinian competition to cooperation, a meaningless universe to a meaningful one, and a disconnected, isolated existence to an interconnected one. In so doing, he shows us that our potential is infinite and calls us to live in accordance with the order of the universe, creating a society based on the cosmic principle of connection, emphasizing cooperation and community.

Physiological roles revealed by ghrelin and ghrelin receptor deficient mice

Science.gov (United States)

Ghrelin is a hormone made in the stomach and known primarily for its growth hormone releasing and orexigenic properties. Nevertheless, ghrelin through its receptor, the GHS-R1a, has been shown to exert many roles including regulation of glucose homeostasis, memory & learning, food addiction and neur...

In situ camera observations reveal major role of zooplankton in modulating marine snow formation during an upwelling-induced plankton bloom

Science.gov (United States)

Taucher, Jan; Stange, Paul; Algueró-Muñiz, María; Bach, Lennart T.; Nauendorf, Alice; Kolzenburg, Regina; Büdenbender, Jan; Riebesell, Ulf

2018-05-01

Particle aggregation and the consequent formation of marine snow alter important properties of biogenic particles (size, sinking rate, degradability), thus playing a key role in controlling the vertical flux of organic matter to the deep ocean. However, there are still large uncertainties about rates and mechanisms of particle aggregation, as well as the role of plankton community structure in modifying biomass transfer from small particles to large fast-sinking aggregates. Here we present data from a high-resolution underwater camera system that we used to observe particle size distributions and formation of marine snow (aggregates >0.5 mm) over the course of a 9-week in situ mesocosm experiment in the Eastern Subtropical North Atlantic. After an oligotrophic phase of almost 4 weeks, addition of nutrient-rich deep water (650 m) initiated the development of a pronounced diatom bloom and the subsequent formation of large marine snow aggregates in all 8 mesocosms. We observed a substantial time lag between the peaks of chlorophyll a and marine snow biovolume of 9-12 days, which is much longer than previously reported and indicates a marked temporal decoupling of phytoplankton growth and marine snow formation during our study. Despite this time lag, our observations revealed substantial transfer of biomass from small particle sizes (single phytoplankton cells and chains) to marine snow aggregates of up to 2.5 mm diameter (ESD), with most of the biovolume being contained in the 0.5-1 mm size range. Notably, the abundance and community composition of mesozooplankton had a substantial influence on the temporal development of particle size spectra and formation of marine snow aggregates: While higher copepod abundances were related to reduced aggregate formation and biomass transfer towards larger particle sizes, the presence of appendicularia and doliolids enhanced formation of large marine snow. Furthermore, we combined in situ particle size distributions with

Attributing Increased River Flooding in the Future: Hydrodynamic Downscaling Reveals Role of Plant Physiological Responses to Increased CO2 is First Order

Science.gov (United States)

Fowler, M. D.; Kooperman, G. J.; Pritchard, M. S.; Randerson, J. T.

2017-12-01

River flooding events, which are the most frequently occurring natural disaster today, are expected to become more frequent and intense in response to climate change. However, the magnitude of these changes remains debated, in part due to uncertainty in our understanding of the physical processes that contribute to these events and their representation in global climate models. While the intensification of precipitation has been shown to be a primary driver of increased flooding, plant physiological responses to increasing CO2 may also play an important role. As the atmospheric concentration of CO2 increases, plants may respond by reducing the width of their stomata (i.e. stomatal conductance), which can decrease water lost through transpiration and in turn maintain higher soil moisture levels. On long timescales, reduced transpiration has been shown to increase average runoff, but on short timescales elevated soil moisture can also increase instantaneous runoff by limiting the rate at which water is able to infiltrate the soil surface. Here, through hydrodynamic downscaling, we isolate the portion of flooding amplification that can be attributed to the physiological response to increasing CO2. This builds on a new analysis that has revealed such physiological effects can rival changes caused by the atmospheric response alone in the tails of the runoff distribution. We use a set of four simulations run with the Community Earth System Model: one pre-industrial control simulation and three others that are forced with four times CO2. In the three climate change simulations, the increased CO2 is applied only to the land-surface, only to the atmosphere, and to both, respectively. Thirty years of daily runoff from these experiments are used as input for the hydrodynamic CaMa-Flood model. Our results reveal that both the radiative and physiological responses to climate change contribute significantly to future changes in flood return period and inundated area. This

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Directory of Open Access Journals (Sweden)

Nelson S. Yee

2015-10-01

Full Text Available The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8 in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca²⁺ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

Potential adjunctive role of radiosynovectomy in primary synovial osteochondromatosis of the knee: A case report

International Nuclear Information System (INIS)

Vadi, Shelvin Kumar; Chouhan, Devendra Kumar; Gorla, Arun Kumar Reddy; Shukla, Jaya; Sood, Ashwani; Mittal, Bhagwant Rai

2017-01-01

Primary synovial osteochondromatosis (PSOC) is a rare but clinically significant cause of morbidity especially in the male population. Surgery is the primary treatment of choice, but the recurrence rate is reported to be high. Moreover, the presence of widespread loose bodies makes it a cumbersome procedure. The complete removal of the disease is tough at times and results in early recurrence. Radiosynovectomy is an established technique for treating various joint arthropathies. The role of radiosynovectomy in case of PSOC has not yet been explored. This case report described the case of a young male with PSOC of the knee joint who was treated with radiosynovectomy for pain relief. The patient reported complete relief from the pain along with significant improvement in joint mobility. The post-therapy three-phase bone scan also validated the reduction in joint inflammation. The patient was taken for surgical removal of the redundant loose bodies after a significant improvement in the pain and reduction in inflammation. Post-therapy radiation fibrosis of the synovium also helped in the en bloc removal of the disease. The role of radiosynovectomy in PSOC needs to be further explored concerning its potential role as an adjuvant to surgical procedures

Potential adjunctive role of radiosynovectomy in primary synovial osteochondromatosis of the knee: A case report

Energy Technology Data Exchange (ETDEWEB)

Vadi, Shelvin Kumar; Chouhan, Devendra Kumar; Gorla, Arun Kumar Reddy; Shukla, Jaya; Sood, Ashwani; Mittal, Bhagwant Rai [Postgraduate Institute of Medical Education and Research, Chandigarh (India)

2017-09-15

Primary synovial osteochondromatosis (PSOC) is a rare but clinically significant cause of morbidity especially in the male population. Surgery is the primary treatment of choice, but the recurrence rate is reported to be high. Moreover, the presence of widespread loose bodies makes it a cumbersome procedure. The complete removal of the disease is tough at times and results in early recurrence. Radiosynovectomy is an established technique for treating various joint arthropathies. The role of radiosynovectomy in case of PSOC has not yet been explored. This case report described the case of a young male with PSOC of the knee joint who was treated with radiosynovectomy for pain relief. The patient reported complete relief from the pain along with significant improvement in joint mobility. The post-therapy three-phase bone scan also validated the reduction in joint inflammation. The patient was taken for surgical removal of the redundant loose bodies after a significant improvement in the pain and reduction in inflammation. Post-therapy radiation fibrosis of the synovium also helped in the en bloc removal of the disease. The role of radiosynovectomy in PSOC needs to be further explored concerning its potential role as an adjuvant to surgical procedures.

Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

Directory of Open Access Journals (Sweden)

Chu Justin

2010-02-01

Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

Molecular characterization and expression of Rab7 from Clonorchis sinensis and its potential role in autophagy.

Science.gov (United States)

Jia, Feifei; Li, Ye; Huang, Yan; Chen, Tingjin; Li, Shan; Xu, Yanquan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2013-07-01

Accumulating evidences suggest that Rab7 GTPase is important for the normal progression of autophagy. However, the role of Rab7 GTPase in regulation of autophagy in Clonorchis sinensis is not known. In this study, a gene encoding Rab7 was isolated from C. sinensis adult cDNA. Recombinant CsRab7 was expressed and purified from Escherichia coli. CsRab7 transcripts were detected in the cDNA of adult worm, metacercaria, cercaria, and egg of C. sinensis, and were highly expressed in the metacercaria. Immunohistochemical localization results revealed that CsRab7 was specifically deposited on the vitellarium and eggs of adult worm. Furthermore, EGFP signal of CsRab7WT and the active mutant CsRab7Q67L were associated with autophagic vesicles in transiently transfected 293T cells. It is concluded from the present study that CsRab7 GTPase possibly contributes to the development of C. sinensis and that the autophagy pathway could be an important site of action with respect to the developmental role of CsRab7 in C. sinensis.

Curcumin and treatment of melanoma: The potential role of microRNAs.

Science.gov (United States)

Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

2017-04-01

Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Smoker identity and its potential role in young adults' smoking behavior: A meta-ethnography.

Science.gov (United States)

Tombor, Ildiko; Shahab, Lion; Herbec, Aleksandra; Neale, Joanne; Michie, Susan; West, Robert

2015-10-01

Identity is an important influence on behavior. To identify potential targets for smoking cessation interventions in young adults, we synthesized findings from qualitative studies on smoker identity and potential influences on smoking and smoking cessation. A systematic search of 4 electronic databases up to September 19, 2013, was conducted to identify qualitative studies on smoker identity in smokers and ex-smokers aged 16-34. Key concepts were extracted from individual studies and synthesized into higher-order interpretations by following the principles of meta-ethnography. Seventeen relevant papers were identified. At the highest level of interpretation, we identified 4 types of findings: (a) contributory factors to identity, (b) identity in relation to smoking, (c) contextual and temporal patterning, and (d) behavior in relation to smoking. Contributory factors included the desire to establish aspirational individual and social identities, enact a smoker identity appropriate to the momentary social context, and alter personal nonsmoking rules when consuming alcohol. Smoker identity was multifaceted and incorporated individuals' defensive rationalizations, and both positive and negative feelings attached to it. Smoker identities took time to develop, were subject to change, and were context dependent. Identity was found to play a role in quit attempts. Qualitative research into the identity of young adult smokers has established it as a multifaceted phenomenon serving important functions but also involving conflict and defensive rationalizations. It develops over time and contextual factors influence its expression. The nature of a smoker's identity can play an important role in smoking cessation. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species.

Science.gov (United States)

Brandt, Christian; Braun, Sascha D; Stein, Claudia; Slickers, Peter; Ehricht, Ralf; Pletz, Mathias W; Makarewicz, Oliwia

2017-02-24

The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics.

Assessment of the Bacteriocinogenic Potential of Marine Bacteria Reveals Lichenicidin Production by Seaweed-Derived Bacillus spp.

Directory of Open Access Journals (Sweden)

Gillian E. Gardiner

2012-10-01

Full Text Available The objectives of this study were (1 to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2 to identify at least some of the bacteriocins produced, if any and (3 to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins.

The Role of polarized positrons and electrons in revealing fundamental interactions at the linear collider

CERN Document Server

Moortgat-Pick, G.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke, J.; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, Tyler McMillan; Dreiner, H.K.; Eberl, H.; Ellis, John R.; Flottmann, K.; Fraas, H.; Franco-Sollova, F.; Franke, F.; Freitas, A.; Goodson, J.; Gray, J.; Han, A.; Heinemeyer, S.; Hesselbach, S.; Hirose, T.; Hohenwarter-Sodek, K.; Juste, A.; Kalinowski, J.; Kernreiter, T.; Kittel, O.; Kraml, S.; Langenfeld, U.; Majerotto, W.; Martinez, A.; Martyn, H.U.; Mikhailichenko, A.; Milstene, C.; Menges, W.; Meyners, N.; Monig, K.; Moffeit, K.; Moretti, S.; Nachtmann, O.; Nagel, F.; Nakanishi, T.; Nauenberg, U.; Nowak, H.; Omori, T.; Osland, P.; Pankov, A.A.; Paver, N.; Pitthan, R.; Poschl, R.; Porod, W.; Proulx, J.; Richardson, P.; Riemann, S.; Rindani, S.D.; Rizzo, T.G.; Schalicke, A.; Schuler, P.; Schwanenberger, C.; Scott, D.; Sheppard, J.; Singh, R.K.; Sopczak, A.; Spiesberger, H.; Stahl, A.; Steiner, H.; Wagner, A.; Weber, A.M.; Weiglein, G.; Wilson, G.W.; Woods, M.; Zerwas, P.; Zhang, J.; Zomer, F.

2008-01-01

The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.

The Role of polarized positrons and electrons in revealing fundamental interactions at the linear collider

Energy Technology Data Exchange (ETDEWEB)

Moortgat-Pick, G.; /CERN /Durham U., IPPP; Abe, T.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke,; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, T.; Eberl, H.; Ellis, John R.; Flottman, K.; Frass, H.; /CERN /Durham U., IPPP /Colorado U. /Tel-Aviv

2005-07-01

The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.

Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin

Directory of Open Access Journals (Sweden)

Rebecca Yee

2015-12-01

Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

Science.gov (United States)

Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uncovering middle managers' role in healthcare innovation implementation.

Science.gov (United States)

Birken, Sarah A; Lee, Shoou-Yih Daniel; Weiner, Bryan J

2012-04-03

Middle managers have received little attention in extant health services research, yet they may have a key role in healthcare innovation implementation. The gap between evidence of effective care and practice may be attributed in part to poor healthcare innovation implementation. Investigating middle managers' role in healthcare innovation implementation may reveal an opportunity for improvement. In this paper, we present a theory of middle managers' role in healthcare innovation implementation to fill the gap in the literature and to stimulate research that empirically examines middle managers' influence on innovation implementation in healthcare organizations. Extant healthcare innovation implementation research has primarily focused on the roles of physicians and top managers. Largely overlooked is the role of middle managers. We suggest that middle managers influence healthcare innovation implementation by diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation. Teamwork designs have become popular in healthcare organizations. Because middle managers oversee these team initiatives, their potential to influence innovation implementation has grown. Future research should investigate middle managers' role in healthcare innovation implementation. Findings may aid top managers in leveraging middle managers' influence to improve the effectiveness of healthcare innovation implementation.

Streaming potential revisited: the influence of convection on the surface conductivity.

Science.gov (United States)

Saini, Rakesh; Garg, Abhinandan; Barz, Dominik P J

2014-09-16

Electrokinetic phenomena play an important role in the electrical characterization of surfaces. In terms of planar or porous substrates, streaming potential and/or streaming current measurements can be used to determine the zeta potential of the substrates in contact with aqueous electrolytes. In this work, we perform electrical impedance spectroscopy measurements to infer the electrical resistance in a microchannel with the same conditions as for a streaming potential experiment. Novel correlations are derived to relate the streaming current and streaming potential to the Reynolds number of the channel flow. Our results not only quantify the influence of surface conductivity, and here especially the contribution of the stagnant layer, but also reveal that channel resistance and therefore zeta potential are influenced by the flow in the case of low ionic strengths. We conclude that convection can have a significant impact on the electrical double layer configuration which is reflected by changes in the surfaces conductivity.

Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.

Science.gov (United States)

Sartawi, Ziad; Schipani, Ernestina; Ryan, Katie B; Waeber, Christian

2017-11-01

The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential role of ABC-assisted repositories in U.S. plutonium and high-level waste disposition

Energy Technology Data Exchange (ETDEWEB)

Berwald, D.; Favale, A.; Myers, T. [Grumman Aerospace Corporation, Bethpage, NY (United States)] [and others

1995-10-01

This paper characterizes the issues involving deep geologic disposal of LWR spent fuel rods, then presents results of an investigation to quantify the potential role of Accelerator-Based Conversion (ABC) in an integrated national nuclear materials and high level waste disposition strategy. The investigation used the deep geological repository envisioned for Yucca Mt., Nevada as a baseline and considered complementary roles for integrated ABC transmutation systems. The results indicate that although a U.S. geologic waste repository will continue to be required, waste partitioning and accelerator transmutation of plutonium, the minor actinides, and selected long-lived fission products can result in the following substantial benefits: plutonium burndown to near zero levels, a dramatic reduction of the long term hazard associated with geologic repositories, an ability to place several-fold more high level nuclear waste in a single repository, electricity sales to compensate for capital and operating costs.

Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

Directory of Open Access Journals (Sweden)

David Juan

2016-02-01

Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth*

Science.gov (United States)

Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin

2015-01-01

The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508

Set potential regulation reveals additional oxidation peaks of Geobacter sulfurreducens anodic biofilms

KAUST Repository

Zhu, Xiuping; Yates, Matthew D.; Logan, Bruce E.

2012-01-01

larger range of set potentials was used to acclimate electroactive biofilms. The potentials of oxidation peaks obtained with G. sulfurreducens biofilms acclimated at 0.60 V (vs. Ag/AgCl) were different from those that developed at - 0.46 V, and both

A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study.

Science.gov (United States)

Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan

2015-06-01

Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. © 2015 Wiley Periodicals, Inc.

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1998-06-01

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

Transcriptomic variation in a coral reveals pathways of clonal organisation

DEFF Research Database (Denmark)

K Bay, Line; Nielsen, Henrik Bjørn; Jarmer, Hanne Østergaard

2009-01-01

A microarray study was undertaken to examine the potential for clonal gene expression variation in a branching reef building coral, Acropora millepora. The role of small-scale gradients in light and water flow was examined by comparing gene expression levels between branch elevation (tip and base......) and position (centre and edge) of replicate coral colonies (n=3). Analyses of variance revealed that almost 60% of variation in gene expression was present between colonies and 34 genes were considered differentially expressed between colonies (minimum P=6.5 x 10(-4)). These genes are associated with energy...... of corymbose-like branching coral colonies such as A. millepora. Four genes were differentially expressed between the tip and base of branches (P=3.239 x 10(-4)) and were associated with lysosome lipase activity and fluorescence, suggesting that branch tips may encounter higher pathogen loads or levels...

Potential role of green tea catechins in the management of oxidative stress-associated infertility.

Science.gov (United States)

Roychoudhury, Shubhadeep; Agarwal, Ashok; Virk, Gurpriya; Cho, Chak-Lam

2017-05-01

Reactive oxygen species (ROS) are present in low concentrations in the genital tracts of males and females. Excessive ROS lead to oxidative stress, which damages DNA, lipids and proteins. Such molecular changes result in compromised vitality, increased morphological defects and decreased sperm motility in the male. In the female, oxidative stress interferes with oocyte maturation, and may inhibit in-vitro maturation of the oocyte. Recently, green tea supplementation has been reported to possess properties that may improve the quality of male and female gametes largely due to the ability of catechin polyphenols to quench ROS. Epigallocatechin-3-gallate (EGCG) is considered the most promising bioactive compound in green tea due to its strong antioxidant activity. The unique property of green tea catechins may potentially improve reproductive health and pose an important research area. We present a comprehensive overview on the effects and potential roles of green tea catechins on oxidative stress in male and female reproduction and fertility. In this review, possible mechanisms of action are highlighted to better understand the potential use of green tea catechins in the reduction of oxidative stress and its associated beneficial effects in the clinical setting. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The current and potential impact of genetics and genomics on neuropsychopharmacology.

Science.gov (United States)

Harrison, Paul J

2015-05-01

One justification for the major scientific and financial investments in genetic and genomic studies in medicine is their therapeutic potential, both for revealing novel targets for drugs which treat the disease process, as well as allowing for more effective and safe use of existing medications. This review considers the extent to which this promise has yet been realised within psychopharmacology, how things are likely to develop in the foreseeable future, and the key issues involved. It draws primarily on examples from schizophrenia and its treatments. One observation is that there is evidence for a range of genetic influences on different aspects of psychopharmacology in terms of discovery science, but far less evidence that meets the standards required before such discoveries impact upon clinical practice. One reason is that results reveal complex genetic influences that are hard to replicate and usually of very small effect. Similarly, the slow progress being made in revealing the genes that underlie the major psychiatric syndromes hampers attempts to apply the findings to identify novel drug targets. Nevertheless, there are some intriguing positive findings of various kinds, and clear potential for genetics and genomics to play an increasing and major role in psychiatric drug discovery. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Analysis reveals potential rangeland impacts if Williamson Act eliminated

Directory of Open Access Journals (Sweden)

William C. Wetzel

2012-10-01

Full Text Available California budget cuts have resulted in dramatic reductions in state funding for the Williamson Act, a land protection program that reduces property taxes for the owners of 15 million acres of California farms and rangeland. With state reimbursements to counties eliminated, the decision to continue Williamson Act contracts lies with individual counties. We investigated the consequences of eliminating the Williamson Act, using a geospatial analysis and a mail questionnaire asking ranchers for plans under a hypothetical elimination scenario. The geospatial analysis revealed that 72% of rangeland parcels enrolled in Williamson Act contracts contained habitat important for statewide conservation goals. Presented with the elimination scenario, survey respondents reported an intention to sell 20% of their total 496,889 acres. The tendency of survey participants to respond that they would sell land was highest among full-time ranchers with low household incomes and without off-ranch employment. A majority (76% of the ranchers who reported that they would sell land predicted that the buyers would develop it for nonagricultural uses, suggesting substantial changes to California's landscape in a future without the Williamson Act.

Third Year Medical School Students' Experiences of Revealing Patients' Stories through Role Playing.

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Cansever, Zeliha; Avsar, Zeynep; Tastan, Kenan

2015-02-01

Studying medicine is hard and it takes longer time compared to other majors. In addition, medical students find medical education boring. It is now necessary to turn medical education into an enjoyable and interesting way. The aim of this study is to evaluate the impact of an educational program related to how to learn taking medical history and how an effective patient-doctor interview should be. The program is structured in various scenarios, on the students learning skills, by the "role playing" method. A scenario prepared by the lecturer was employed in this study. While one of the students acted in a doctor role, the other one played in the role of patient's relative. The lecturer always played in the role of patient. After performing the role playing, students' written and oral feedbacks were gathered. Data were analysed by using SPSS 20.0 program. A total of 470 feedbacks (51.3% were given by the female students) were taken from the students. Thirty-three volunteer students, nineteen of them were male, took part in the role playing. In the patient-doctor interview, the field that students were best were greeting the patients and dealing only with patients during the examination. The mean scores were 3.81±0.95 and 3.79±0.94 respectively. The ability to "summarize" and to "address the patient with his/her name" had the lowest scores; the mean scores of the students in these areas were 2.94±1.11 and 2.70±1.31, respectively. Medical education is a long and tough process. Therefore, it should be interesting, attention getting and cheerful. Role playing can be effective in meeting that need.

Three-dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin in vivo.

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Schwarz, Mathias; Buehler, Andreas; Aguirre, Juan; Ntziachristos, Vasilis

2016-01-01

Optical imaging plays a major role in disease detection in dermatology. However, current optical methods are limited by lack of three-dimensional detection of pathophysiological parameters within skin. It was recently shown that single-wavelength optoacoustic (photoacoustic) mesoscopy resolves skin morphology, i.e. melanin and blood vessels within epidermis and dermis. In this work we employed illumination at multiple wavelengths for enabling three-dimensional multispectral optoacoustic mesoscopy (MSOM) of natural chromophores in human skin in vivo operating at 15-125 MHz. We employ a per-pulse tunable laser to inherently co-register spectral datasets, and reveal previously undisclosed insights of melanin, and blood oxygenation in human skin. We further reveal broadband absorption spectra of specific skin compartments. We discuss the potential of MSOM for label-free visualization of physiological biomarkers in skin in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential roles for uncoupling proteins in HIV lipodystrophy.

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Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

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Machado, Henrique; Gram, Lone

2017-01-01

Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

Integrated metagenomic and physiochemical analyses to evaluate the potential role of microbes in the sand filter of a drinking water treatment system.

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Yaohui Bai

Full Text Available While sand filters are widely used to treat drinking water, the role of sand filter associated microorganisms in water purification has not been extensively studied. In the current investigation, we integrated molecular (based on metagenomic and physicochemical analyses to elucidate microbial community composition and function in a common sand filter used to treat groundwater for potable consumption. The results revealed that the biofilm developed rapidly within 2 days (reaching ≈ 10(11 prokaryotes per gram in the sand filter along with abiotic and biotic particulates accumulated in the interstitial spaces. Bacteria (up to 90% dominated the biofilm microbial community, with Alphaproteobacteria being the most common class. Thaumarchaeota was the sole phylum of Archaea, which might be involved in ammonia oxidation. Function annotation of metagenomic datasets revealed a number of aromatic degradation pathway genes, such as aromatic oxygenase and dehydrogenase genes, in the biofilm, suggesting a significant role for microbes in the breakdown of aromatic compounds in groundwater. Simultaneous nitrification and denitrification pathways were confirmed as the primary routes of nitrogen removal. Dissolved heavy metals in groundwater, e.g. Mn(2+ and As(3+, might be biologically oxidized to insoluble or easily adsorbed compounds and deposited in the sand filter. Our study demonstrated that the role of the microbial community in the sand filter treatment system are critical to effective water purification in drinking water.

Integrated metagenomic and physiochemical analyses to evaluate the potential role of microbes in the sand filter of a drinking water treatment system.

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Bai, Yaohui; Liu, Ruiping; Liang, Jinsong; Qu, Jiuhui

2013-01-01

While sand filters are widely used to treat drinking water, the role of sand filter associated microorganisms in water purification has not been extensively studied. In the current investigation, we integrated molecular (based on metagenomic) and physicochemical analyses to elucidate microbial community composition and function in a common sand filter used to treat groundwater for potable consumption. The results revealed that the biofilm developed rapidly within 2 days (reaching ≈ 10(11) prokaryotes per gram) in the sand filter along with abiotic and biotic particulates accumulated in the interstitial spaces. Bacteria (up to 90%) dominated the biofilm microbial community, with Alphaproteobacteria being the most common class. Thaumarchaeota was the sole phylum of Archaea, which might be involved in ammonia oxidation. Function annotation of metagenomic datasets revealed a number of aromatic degradation pathway genes, such as aromatic oxygenase and dehydrogenase genes, in the biofilm, suggesting a significant role for microbes in the breakdown of aromatic compounds in groundwater. Simultaneous nitrification and denitrification pathways were confirmed as the primary routes of nitrogen removal. Dissolved heavy metals in groundwater, e.g. Mn(2+) and As(3+), might be biologically oxidized to insoluble or easily adsorbed compounds and deposited in the sand filter. Our study demonstrated that the role of the microbial community in the sand filter treatment system are critical to effective water purification in drinking water.

The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases

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Catia Dini

2012-01-01

Full Text Available INTRODUCTION: Vitamin D deficiency (VDD is a common condition among several populations in the world. VDD is associated with higher incidence of immune system disorders and faster progression of some infectious diseases. Vitamin D is known to be of physiological importance, it is considered an essential micronutrient for the bone health and plays a beneficial role in the prevention and/or treatment of a number of chronic diseases. Vitamin D has a complex action on the immune system. RESULTS: Evidence that vitamin D protects against tuberculosis has been supported by in vitro, epidemiological and some preliminary clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency virus and plays a crucial role in the defence against respiratory infections. CONCLUSIONS: Vitamin D supplementation could be a low-cost, practical method to protect groups of people with high incidence of those diseases. Public health education should stress the need for adequate dietary intake of vitamin D in those vulnerable groups.

The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases.

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Dini, Catia; Bianchi, Antonio

2012-01-01

Vitamin D deficiency (VDD) is a common condition among several populations in the world. VDD is associated with higher incidence of immune system disorders and faster progression of some infectious diseases. Vitamin D is known to be of physiological importance, it is considered an essential micronutrient for the bone health and plays a beneficial role in the prevention and/or treatment of a number of chronic diseases. Vitamin D has a complex action on the immune system. Evidence that vitamin D protects against tuberculosis has been supported by in vitro, epidemiological and some preliminary clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency virus) and plays a crucial role in the defence against respiratory infections. Vitamin D supplementation could be a low-cost, practical method to protect groups of people with high incidence of those diseases. Public health education should stress the need for adequate dietary intake of vitamin D in those vulnerable groups.

Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

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Ajeet Mandal

Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

KAUST Repository

Ichim-Moreno, Norú

2010-05-01

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently, glucocorticoids are the only available treatment for DMD, but they have been shown to result in serious side effects. The purpose of this research was to define a core signature of gene expression related to DMD via integrative analysis of mouse and human datasets. This core signature was subsequently used to screen for novel potential compounds that antagonistically affect the expression of signature genes. With this approach we were able to identify compounds that are 1) already used to treat DMD, 2) currently under investigation for treatment, and 3) so far unknown but promising candidates. Our study highlights the potential of meta-analyses through the combination of datasets to unravel previously unrecognized associations and reveal new relationships. © IEEE.

The role of information technologies in the development of school social education practice

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Selivanova Natalia L.

2016-01-01

Full Text Available The paper discusses various ways and specifics of applying information technologies in the process of school students’ social education and reveals the role of IT in the development of the student’s personality. Special attention is paid to the social education potential of network communities, the internet, virtual museums and mobile technologies. The paper also explains the risks of information technologies in social education.

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome

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Frédéric Pontvianne

2016-08-01

Full Text Available The nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS and identified nucleolus-associated chromatin domains (NADs by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1. NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs, sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance.

Identification of nucleolus-associated chromatin domains reveals the role of the nucleolus in the 3D organisation of the A. thaliana genome

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Pontvianne, Frédéric; Carpentier, Marie-Christine; Durut, Nathalie; Pavlištová, Veronika; Jaške, Karin; Schořová, Šárka; Parrinello, Hugues; Rohmer, Marine; Pikaard, Craig S; Fojtová, Miloslava; Fajkus, Jiří; Saez-Vasquez, Julio

2017-01-01

The nucleolus is the site of ribosomal RNA (rRNA) gene transcription, rRNA processing and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli by Fluorescence Activated Cell Sorting (FACS) and identified Nucleolus-Associated Chromatin Domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein, NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions and mostly inactive protein-coding genes. However, NADs also include active ribosomal RNA genes, and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance. PMID:27477271

Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome.

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Pontvianne, Frédéric; Carpentier, Marie-Christine; Durut, Nathalie; Pavlištová, Veronika; Jaške, Karin; Schořová, Šárka; Parrinello, Hugues; Rohmer, Marine; Pikaard, Craig S; Fojtová, Miloslava; Fajkus, Jiří; Sáez-Vásquez, Julio

2016-08-09

The nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS) and identified nucleolus-associated chromatin domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Historical forest baselines reveal potential for continued carbon sequestration

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Rhemtulla, Jeanine M.; Mladenoff, David J.; Clayton, Murray K.

2009-01-01

One-third of net CO2 emissions to the atmosphere since 1850 are the result of land-use change, primarily from the clearing of forests for timber and agriculture, but quantifying these changes is complicated by the lack of historical data on both former ecosystem conditions and the extent and spatial configuration of subsequent land use. Using fine-resolution historical survey records, we reconstruct pre-EuroAmerican settlement (1850s) forest carbon in the state of Wisconsin, examine changes in carbon after logging and agricultural conversion, and assess the potential for future sequestration through forest recovery. Results suggest that total above-ground live forest carbon (AGC) fell from 434 TgC before settlement to 120 TgC at the peak of agricultural clearing in the 1930s and has since recovered to approximately 276 TgC. The spatial distribution of AGC, however, has shifted significantly. Former savanna ecosystems in the south now store more AGC because of fire suppression and forest ingrowth, despite the fact that most of the region remains in agriculture, whereas northern forests still store much less carbon than before settlement. Across the state, continued sequestration in existing forests has the potential to contribute an additional 69 TgC. Reforestation of agricultural lands, in particular, the formerly high C-density forests in the north-central region that are now agricultural lands less optimal than those in the south, could contribute 150 TgC. Restoring historical carbon stocks across the landscape will therefore require reassessing overall land-use choices, but a range of options can be ranked and considered under changing needs for ecosystem services. PMID:19369213

Bovine mastitis disease/pathogenicity: evidence of the potential role of microbial biofilms.

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Gomes, Fernanda; Saavedra, Maria José; Henriques, Mariana

2016-04-01

Bovine mastitis (BM) is a disease with high incidence worldwide and one of the most relevant bovine pathologies and the most costly to the dairy industry. BM is an inflammation of the udder and represents one of the most difficult veterinary diseases to control. Biofilm formation is considered a selective advantage for pathogens causing mastitis, facilitating bacterial persistence in the udder. In fact, recently some authors drew attention to the biofilm formation ability presented by several mastitis causing pathogens and to its possible relation with recurrent mastitis infections and with the increased resistance to antimicrobial agents and host immune defence system. Actually, up to now, several researchers reported the potential role of cells in this mode of growth in the previous facts mentioned. As a consequence of the presence of biofilms, the infection here focused is more difficult to treat and eradicate, making this problem a more relevant pressing issue. Thus, we believe that a deeper knowledge of these structures in mastitis can help to determine the best control strategy to be used in veterinary practice in order to reduce losses in the dairy industry and to ensure milk safety and quality. The aim of this paper was to review the existing research and consequently to provide an overview of the role of biofilms in BM infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in Allo- and Autoimmunity

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Qi Zhang

2015-01-01

Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of cells that consists of myeloid progenitor cells and immature myeloid cells. They have been identified as a cell population that may affect the activation of CD4+ and CD8+ T-cells to regulate the immune response negatively, which makes them attractive targets for the treatment of transplantation and autoimmune diseases. Several studies have suggested the potential suppressive effect of MDSCs on allo- and autoimmune responses. Conversely, MDSCs have also been found at various stages of differentiation, accumulating during pathological situations, not only during tumor development but also in a variety of inflammatory immune responses, bone marrow transplantation, and some autoimmune diseases. These findings appear to be contradictory. In this review, we summarize the roles of MDSCs in different transplantation and autoimmune diseases models as well as the potential to target these cells for therapeutic benefit.

A Potential Role for Exosomal TCTP Export in Vascular Remodeling in Pulmonary Arterial Hypertension.

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Ferrer, Elisabet; Dunmore, Benjamin J; Hassan, Dhiya; Ormiston, Mark L; Moore, Stephen; Deighton, John; Long, Lu; Yang, Xu Dong; Stewart, Duncan J; Morrell, Nicholas W

2018-04-20

Pulmonary arterial hypertension (PAH) is characterized by increased proliferation and resistance to apoptosis of pulmonary vascular cells. Increased expression of translationally controlled tumor protein (TCTP), a pro-survival and anti-apoptotic mediator, has recently been demonstrated in patients with hereditary PAH (HPAH) although its role in the pathobiology of PAH remains unclear. Silencing of TCTP in blood outgrowth endothelial cells (BOECs) isolated from control subjects led to significant changes in morphology, cytoskeletal organization, increased apoptosis and decreased directionality during migration. As TCTP is also localized in extracellular vesicles (EVs), we isolated BOEC-derived EVs (exosomes and microparticles) by sequential ultracentrifugation. BOECs isolated from patients harboring BMPR2 mutations released more exosomes than controls in pro-apoptotic conditions. Furthermore, TCTP protein expression was significantly higher in exosomes compared to microparticles, indicating that TCTP is mainly exported via exosomes. Co-culture assays demonstrated that exosomes transferred TCTP from endothelial cells (ECs) to pulmonary artery smooth muscle cells (PASMCs) suggesting a role for endothelial-derived TCTP in conferring proliferation and apoptotic resistance. In an experimental model of PAH, rats treated with monocrotaline demonstrated increased concentrations of TCTP in the lung and plasma. Consistent with this finding, we observed increased circulating TCTP levels in patients with IPAH compared with controls. Therefore, our data suggests an important role for TCTP in regulating the critical vascular cell phenotypes implicated in the pathobiology of PAH. In addition, this research implicates TCTP as a potential biomarker for the onset and development of PAH.

Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

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Nirmal, J; Singh, S B; Biswas, N R; Thavaraj, V; Azad, R V; Velpandian, T

2013-01-01

Purpose We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. Methods New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70–100 μl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. Results Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. Conclusion OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics. PMID:23846373

Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

International Nuclear Information System (INIS)

Sun, Haiyan; Li, Ying; Feng, Shengqiu; Zou, Weihua; Guo, Kai; Fan, Chunfen; Si, Shengli

2013-01-01

Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid

Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

Energy Technology Data Exchange (ETDEWEB)

Sun, Haiyan [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); School of Biology and Food Engineering, Changshu Institute of Technology, Changshu 215500 (China); Li, Ying; Feng, Shengqiu; Zou, Weihua [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Guo, Kai [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Fan, Chunfen [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Si, Shengli [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); and others

2013-01-18

Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid.

Socio-motivational moderators – Two sides of the same coin?Testing the potential buffering role of socio-motivational relationships on achievement drive and test anxiety among German and Canadian secondary school students

Directory of Open Access Journals (Sweden)

Frances eHoferichter

2015-10-01

Full Text Available The current cross-national study investigates the potential buffering role of socio-motivational relationships for the association of achievement drive and test anxiety in secondary school students from Canada and Germany. One thousand eighty-eight students (54% girls, Mage = 13.71, SD = .53, age span 12–15 years from the state of Brandenburg and 389 students from Quebéc (55.9% girls, Mage = 13.43, SD = .82, age span 12–16 years were asked about their socio-motivational relationships with their teachers and peers, their drive for achievement, and test anxiety. Multigroup latent moderated structural equations (MGLMS were conducted to test for the moderator role of socio-motivational relationships that would buffer feelings of test anxiety related to the drive for achievement. The analyses revealed the two-sided role socio-motivational relationships can have for students with different levels of achievement drive; intensifying or mitigating feelings of test anxiety. Thereby, the results of this study extend the buffering hypothesis by Cohen and Wills (1985. Cross-national differences between Canada and Germany were found concerning the studied moderators on the association of achievement drive and test anxiety: While for German students teacher-student relationships acted as moderator, for Canadian students student-student relationships and teachers acting as positive motivators displayed a moderator role.

Nonstructural leaf carbohydrate dynamics of Pinus edulis during drought-induced tree mortality reveal role for carbon metabolism in mortality mechanism.

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Adams, Henry D; Germino, Matthew J; Breshears, David D; Barron-Gafford, Greg A; Guardiola-Claramonte, Maite; Zou, Chris B; Huxman, Travis E

2013-03-01

Vegetation change is expected with global climate change, potentially altering ecosystem function and climate feedbacks. However, causes of plant mortality, which are central to vegetation change, are understudied, and physiological mechanisms remain unclear, particularly the roles of carbon metabolism and xylem function. We report analysis of foliar nonstructural carbohydrates (NSCs) and associated physiology from a previous experiment where earlier drought-induced mortality of Pinus edulis at elevated temperatures was associated with greater cumulative respiration. Here, we predicted faster NSC decline for warmed trees than for ambient-temperature trees. Foliar NSC in droughted trees declined by 30% through mortality and was lower than in watered controls. NSC decline resulted primarily from decreased sugar concentrations. Starch initially declined, and then increased above pre-drought concentrations before mortality. Although temperature did not affect NSC and sugar, starch concentrations ceased declining and increased earlier with higher temperatures. Reduced foliar NSC during lethal drought indicates a carbon metabolism role in mortality mechanism. Although carbohydrates were not completely exhausted at mortality, temperature differences in starch accumulation timing suggest that carbon metabolism changes are associated with time to death. Drought mortality appears to be related to temperature-dependent carbon dynamics concurrent with increasing hydraulic stress in P. edulis and potentially other similar species. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

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Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

2016-01-01

The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.

Science.gov (United States)

Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

2014-09-12

Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects. Copyright © 2014 Elsevier Inc. All rights reserved.

The potential role of natural gas power plants with carbon capture and storage as a bridge to a low-carbon future

Data.gov (United States)

U.S. Environmental Protection Agency — This dataset represents the data underlying the figures presented in the manuscript "The potential role of natural gas power plants with carbon capture and storage...

Metabolomics reveals metabolic biomarkers of Crohn's disease

Energy Technology Data Exchange (ETDEWEB)

Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

2009-06-01

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

Beyond gender stereotypes in language comprehension: self sex-role descriptions affect the brain's potentials associated with agreement processing

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Paolo eCanal

2015-12-01

Full Text Available We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as king or engineer or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female, or stereotypical (a nurse is likely to be female. When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the ERP response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more feminine or expressive self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less expressive participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent.

Understanding Cortisol Reactivity across the Day at Child Care: The Potential Buffering Role of Secure Attachments to Caregivers

Science.gov (United States)

Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

2012-01-01

Full-day center-based child care has been repeatedly associated with rising cortisol across the child care day. This study addressed the potential buffering role of attachment to mothers and lead teachers in 110 preschoolers while at child care. Using multi-level modeling and controlling for a number of child, family, and child care factors,…

Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

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Couturier Marie

2012-02-01

Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

The potential roles of endogenous retroviruses in autoimmunity.

Science.gov (United States)

Nakagawa, K; Harrison, L C

1996-08-01

Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically

Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

Science.gov (United States)

Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

2017-09-01

Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancing the care navigation model: potential roles for health sciences librarians

Science.gov (United States)

Huber, Jeffrey T.; Shapiro, Robert M.; Burke, Heather J.; Palmer, Aaron

2014-01-01

This study analyzed the overlap between roles and activities that health care navigators perform and competencies identified by the Medical Library Association's (MLA's) educational policy statement. Roles and activities that health care navigators perform were gleaned from published literature. Once common roles and activities that health care navigators perform were identified, MLA competencies were mapped against those roles and activities to identify areas of overlap. The greatest extent of correspondence occurred in patient empowerment and support. Further research is warranted to determine the extent to which health sciences librarians might assume responsibility for roles and activities that health care navigators perform. PMID:24415921

The glossyhead1 allele of acc1 reveals a principal role for multidomain acetyl-coenzyme a carboxylase in the biosynthesis of cuticular waxes by Arabidopsis

KAUST Repository

Lu, Shiyou

2011-09-23

A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy inflorescence stems, postgenital fusion in floral organs, and reduced fertility, was isolated from an ethyl methanesulfonate-mutagenized population and designated glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to our knowledge, is the first mutant allele of ACC1 that does not cause lethality at the seed or early germination stage, allowing for the first time a detailed analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1 organs revealed a primary role for ACC1 in the biosynthesis of the very-long-chain fatty acids (C 20:0 or longer) associated with cuticular waxes and triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has limited impact on any lipid metabolic networks but instead has a large effect on environmental stress-responsive pathways, especially senescence and ethylene synthesis determinants, indicating a possible role for the cytosolic malonyl-coenzyme A-derived lipids in stress response signaling. © 2011 American Society of Plant Biologists. All Rights Reserved.

The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

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Chengcheng Liu

2017-06-01

Full Text Available Periodontitis is a chronic inflammatory disease that causes damage to periodontal tissues, which include the gingiva, periodontal ligament, and alveolar bone. The major cause of periodontal tissue destruction is an inappropriate host response to microorganisms and their products. Specifically, a homeostatic imbalance between reactive oxygen species (ROS and antioxidant defense systems has been implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as intracellular signal transducers result in autophagy, which plays a dual role in periodontitis by promoting cell death or blocking apoptosis in infected cells. Autophagy can also regulate ROS generation and scavenging. Investigations are ongoing to elucidate the crosstalk mechanisms between ROS and autophagy. Here, we review the physiological and pathological roles of ROS and autophagy in periodontal tissues. The redox-sensitive pathways related to autophagy, such as mTORC1, Beclin 1, and the Atg12-Atg5 complex, are explored in depth to provide a comprehensive overview of the crosstalk between ROS and autophagy. Based on the current evidence, we suggest that a potential linkage between ROS and autophagy is involved in the pathogenesis of periodontitis.

Genome-Resolved Metagenomic Analysis Reveals Roles for Candidate Phyla and Other Microbial Community Members in Biogeochemical Transformations in Oil Reservoirs

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Ping Hu

2016-01-01

Full Text Available Oil reservoirs are major sites of methane production and carbon turnover, processes with significant impacts on energy resources and global biogeochemical cycles. We applied a cultivation-independent genomic approach to define microbial community membership and predict roles for specific organisms in biogeochemical transformations in Alaska North Slope oil fields. Produced water samples were collected from six locations between 1,128 m (24 to 27°C and 2,743 m (80 to 83°C below the surface. Microbial community complexity decreased with increasing temperature, and the potential to degrade hydrocarbon compounds was most prevalent in the lower-temperature reservoirs. Sulfate availability, rather than sulfate reduction potential, seems to be the limiting factor for sulfide production in some of the reservoirs under investigation. Most microorganisms in the intermediate- and higher-temperature samples were related to previously studied methanogenic and nonmethanogenic archaea and thermophilic bacteria, but one candidate phylum bacterium, a member of the Acetothermia (OP1, was present in Kuparuk sample K3. The greatest numbers of candidate phyla were recovered from the mesothermic reservoir samples SB1 and SB2. We reconstructed a nearly complete genome for an organism from the candidate phylum Parcubacteria (OD1 that was abundant in sample SB1. Consistent with prior findings for members of this lineage, the OD1 genome is small, and metabolic predictions support an obligately anaerobic, fermentation-based lifestyle. At moderate abundance in samples SB1 and SB2 were members of bacteria from other candidate phyla, including Microgenomates (OP11, Atribacteria (OP9, candidate phyla TA06 and WS6, and Marinimicrobia (SAR406. The results presented here elucidate potential roles of organisms in oil reservoir biological processes.

Comparative genomics of neuroglobin reveals its early origins.

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Jasmin Dröge

Full Text Available Neuroglobin (Ngb is a hexacoordinated globin expressed mainly in the central and peripheral nervous system of vertebrates. Although several hypotheses have been put forward regarding the role of neuroglobin, its definite function remains uncertain. Ngb appears to have a neuro-protective role enhancing cell viability under hypoxia and other types of oxidative stress. Ngb is phylogenetically ancient and has a substitution rate nearly four times lower than that of other vertebrate globins, e.g. hemoglobin. Despite its high sequence conservation among vertebrates Ngb seems to be elusive in invertebrates.We determined candidate orthologs in invertebrates and identified a globin of the placozoan Trichoplax adhaerens that is most likely orthologous to vertebrate Ngb and confirmed the orthologous relationship of the polymeric globin of the sea urchin Strongylocentrotus purpuratus to Ngb. The putative orthologous globin genes are located next to genes orthologous to vertebrate POMT2 similarly to localization of vertebrate Ngb. The shared syntenic position of the globins from Trichoplax, the sea urchin and of vertebrate Ngb strongly suggests that they are orthologous. A search for conserved transcription factor binding sites (TFBSs in the promoter regions of the Ngb genes of different vertebrates via phylogenetic footprinting revealed several TFBSs, which may contribute to the specific expression of Ngb, whereas a comparative analysis with myoglobin revealed several common TFBSs, suggestive of regulatory mechanisms common to globin genes.Identification of the placozoan and echinoderm genes orthologous to vertebrate neuroglobin strongly supports the hypothesis of the early evolutionary origin of this globin, as it shows that neuroglobin was already present in the placozoan-bilaterian last common ancestor. Computational determination of the transcription factor binding sites repertoire provides on the one hand a set of transcriptional factors that are

POTENTIAL CLUSTERS IN BANAT AND THEIR ROLE IN REGIONAL ECONOMIC DEVELOPMENT

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Ramona IŞFĂNESCU

2010-06-01

Full Text Available The interest in the study of clusters and their role in the economic development of certain regions has constantly grown in the past years. This interest has also been emphasized by the emergence of successful clusters in many regions; these are clusters that have visibly and they have determined the increase in competitiveness of those particular regions. Clusters are geographic gatherings of firms and institutions, connected to each other and specialized in certain fields of activity. In Romania, due to the low cooperation level among enterprises we cannot say that proper clusters exists, but just some “spatial gatherings” of firms activating in certain domains, connected by the need of using certain natural resources and the existence of a specialized workforce in that particular domain. Natural “clusters” can be identified by means of quantitative analyses, these indicating the possibility to identify certain spatial assemblies of firms in a certain economic sector. Starting from these quantitative analyses, for Banat region have been identified some important spatial gatherings of firms activating in certain domains which could represent potential clusters in this area. As clusters function on the principle of cooperation among enterprises, a strong point of the region is the presence of foreign investors which promoted the model of enterprise cooperation through sub-contracting local enterprises. Among these, we mention the Italian investors which brought to Banat, especially to Timiş County the Italian cluster model. Are there in Banat premises for the emergence of clusters? Which are the fields of activity in which these clusters can emerge? What role will these clusters play in the economic development of the region? These are just some of the questions that we aim answering to through this study.

Selected soil enzymes: Examples of their potential roles in the ...

African Journals Online (AJOL)

SERVER

2008-02-05

Feb 5, 2008 ... Soil enzymes regulate ecosystem functioning and in particular play a key role in nutrient cycling. In ... A better understanding of the role of these soil enzyme- es activity ..... measure of any disruption caused by pesticides, trace.

Uncovering middle managers' role in healthcare innovation implementation

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Birken Sarah A

2012-04-01

Full Text Available Abstract Background Middle managers have received little attention in extant health services research, yet they may have a key role in healthcare innovation implementation. The gap between evidence of effective care and practice may be attributed in part to poor healthcare innovation implementation. Investigating middle managers' role in healthcare innovation implementation may reveal an opportunity for improvement. In this paper, we present a theory of middle managers' role in healthcare innovation implementation to fill the gap in the literature and to stimulate research that empirically examines middle managers' influence on innovation implementation in healthcare organizations. Discussion Extant healthcare innovation implementation research has primarily focused on the roles of physicians and top managers. Largely overlooked is the role of middle managers. We suggest that middle managers influence healthcare innovation implementation by diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation. Summary Teamwork designs have become popular in healthcare organizations. Because middle managers oversee these team initiatives, their potential to influence innovation implementation has grown. Future research should investigate middle managers' role in healthcare innovation implementation. Findings may aid top managers in leveraging middle managers' influence to improve the effectiveness of healthcare innovation implementation.

Uncovering middle managers' role in healthcare innovation implementation

Science.gov (United States)

2012-01-01

Background Middle managers have received little attention in extant health services research, yet they may have a key role in healthcare innovation implementation. The gap between evidence of effective care and practice may be attributed in part to poor healthcare innovation implementation. Investigating middle managers' role in healthcare innovation implementation may reveal an opportunity for improvement. In this paper, we present a theory of middle managers' role in healthcare innovation implementation to fill the gap in the literature and to stimulate research that empirically examines middle managers' influence on innovation implementation in healthcare organizations. Discussion Extant healthcare innovation implementation research has primarily focused on the roles of physicians and top managers. Largely overlooked is the role of middle managers. We suggest that middle managers influence healthcare innovation implementation by diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation. Summary Teamwork designs have become popular in healthcare organizations. Because middle managers oversee these team initiatives, their potential to influence innovation implementation has grown. Future research should investigate middle managers' role in healthcare innovation implementation. Findings may aid top managers in leveraging middle managers' influence to improve the effectiveness of healthcare innovation implementation. PMID:22472001

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

Science.gov (United States)

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

2015-06-17

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

The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy.

Science.gov (United States)

Ficarra, Vincenzo; Rossanese, Marta; Zazzara, Michele; Giannarini, Gianluca; Abbinante, Maria; Bartoletti, Riccardo; Mirone, Vincenzo; Scaglione, Francesco

2014-12-01

A chronic prostatic inflammation seems to play a crucial role in benign prostatic hyperplasia (BPH) pathogenesis and progression. Therefore, inflammation could represent a new potential target for medical therapy of lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH). This review article analyzes the evidence supporting the role of inflammation in the onset and progression of BPH, and it assesses the potential impact of previous mechanisms on medical therapy of LUTS/BPH. Literature data support the role of inflammation as a relevant factor in the pathogenesis of BPH. Indeed, several data favour the role of infiltrating lymphocytes in the development and progression of prostate adenoma as an effect of a self-maintaining remodeling process. Although available drugs commonly used in the treatment of LUTS/BPH do not exhibit an anti-inflammatory activity, it seems to be obvious considering the inflammation as a new target in the treatment of LUTS/BPH. Drugs currently investigated for the treatment of prostatic inflammation include the hexanic lipidosterolic extract of Serenoa repens, nonsteroidal anti-inflammatory drugs, and vitamin D receptor agonists.

The Role of Canonical Transient Receptor Potential Channels in Seizure and Excitotoxicity

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Fang Zheng

2014-04-01

Full Text Available Canonical transient receptor potential (TRPC channels are a family of polymodal cation channels with some degree of Ca2+ permeability. Although initially thought to be channels mediating store-operated Ca2+ influx, TRPC channels can be activated by stimulation of Gq-coupled G-protein coupled receptors, or by an increase in intracellular free Ca2+ concentration. Thus, activation of TRPC channels could be a common downstream event of many signaling pathways that contribute to seizure and excitotoxicity, such as N-methyl-D-aspartate (NMDA receptor-mediated Ca2+ influx, or metabotropic glutamate receptor activation. Recent studies with genetic ablation of various TRPC family members have demonstrated that TRPC channels, in particular heteromeric TRPC1/4 channels and homomeric TRPC5 channels, play a critical role in both pilocarpine-induced acute seizures and neuronal cell death. However, exact underlying mechanisms remain to be fully elucidated, and selective TRPC modulators and antibodies with better specificity are urgently needed for future research.

Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.

Science.gov (United States)

Khan, Mudassar Nawaz; Sakata, Katsumi; Hiraga, Susumu; Komatsu, Setsuko

2014-12-05

Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.

Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal transduction

International Nuclear Information System (INIS)

Han, Gye Won; Bakolitsa, Constantina; Miller, Mitchell D.; Kumar, Abhinav; Carlton, Dennis; Najmanovich, Rafael J.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ernst, Dustin; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Jaroszewski, Lukasz; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structures of SPO0140 and Sbal-2486 revealed a two-domain structure that adopts a novel fold. Analysis of the interdomain cleft suggests a nucleotide-based ligand with a genome context indicating signaling as a possible role for this family. The crystal structures of SPO0140 and Sbal-2486 were determined using the semiautomated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). The structures revealed a conserved core with domain duplication and a superficial similarity of the C-terminal domain to pleckstrin homology-like folds. The conservation of the domain interface indicates a potential binding site that is likely to involve a nucleotide-based ligand, with genome-context and gene-fusion analyses additionally supporting a role for this family in signal transduction, possibly during oxidative stress

Surface Complexation Modeling of Calcite Zeta Potential Measurement in Mixed Brines for Carbonate Wettability Characterization

Science.gov (United States)

Song, J.; Zeng, Y.; Biswal, S. L.; Hirasaki, G. J.

2017-12-01

We presents zeta potential measurements and surface complexation modeling (SCM) of synthetic calcite in various conditions. The systematic zeta potential measurement and the proposed SCM provide insight into the role of four potential determining cations (Mg2+, SO42- , Ca2+ and CO32-) and CO2 partial pressure in calcite surface charge formation and facilitate the revealing of calcite wettability alteration induced by brines with designed ionic composition ("smart water"). Brines with varying potential determining ions (PDI) concentration in two different CO2 partial pressure (PCO2) are investigated in experiments. Then, a double layer SCM is developed to model the zeta potential measurements. Moreover, we propose a definition for contribution of charged surface species and quantitatively analyze the variation of charged species contribution when changing brine composition. After showing our model can accurately predict calcite zeta potential in brines containing mixed PDIs, we apply it to predict zeta potential in ultra-low and pressurized CO2 environments for potential applications in carbonate enhanced oil recovery including miscible CO2 flooding and CO2 sequestration in carbonate reservoirs. Model prediction reveals that pure calcite surface will be positively charged in all investigated brines in pressurized CO2 environment (>1atm). Moreover, the sensitivity of calcite zeta potential to CO2 partial pressure in the various brine is found to be in the sequence of Na2CO3 > Na2SO4 > NaCl > MgCl2 > CaCl2 (Ionic strength=0.1M).

Role of natural antisense transcripts pertaining to tumor suppressor genes in human carcinomas

International Nuclear Information System (INIS)

Pelicci, G.; Pierotti, M.

2009-01-01

Overlapping transcripts in opposite orientations can potentially form perfect sense-antisense duplex RNA. Recently, several studies have revealed the extent of natural antisense transcripts (NATs) and their role in important biological phenomena also in higher organisms. In order to test the hypothesis that the function of NATs in man might represent an essential element in the regulation of gene expression, especially at transcriptional level, in this study we planned to look for, systematically examine, and characterize NATs belonging in the human genome to the tumour suppressor class of genes, so to identify physiological (and potentially pathological) modulators in this gene class

RENEWABLE ENERGY SOURCES AND THEIR POTENTIAL ROLE IN MITIGATION OF CLIMATE CHANGES AND AS A SUSTAINABLE DEVELOPMENT DRIVER IN BOSNIA AND HERZEGOVINA

Directory of Open Access Journals (Sweden)

Petar M Gvero

2010-01-01

Full Text Available Bosnia and Herzegovina have significant physical potential regarding to renewable energy sources. Hydro, biomass, geothermal, wind, and solar potential can play important role in the whole state economy. Bosnia and Herzegovina is Non-Annex I country according to UNFCCC and according to that it is obligated to participate in the global efforts in order to reduce green house gases emission. This paper gives some analysis of the physical, technological, economic, and market potential of renewable energy sources in Bosnia and Herzegovina and their potential role in mitigation of climate changes. Paper also gives the analysis of the potential connections between renewable energy sources and sustainable development of the economy, taking in to consideration specific political structure of the state. Bosnia and Herzegovina is consisting from two entities: Republic of Srpska and Federation of Bosnia and Herzegovina, and Brcko District; energy sector and climate changes mitigation measures are under their jurisdiction. According to that some of this paper results can be useful for the improvement of entity and state strategies with the final aim to place renewable energy sources on the right position, as some of the major economy drivers, not only in Bosnia and Herzegovina, but in whole region.

Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens.

Science.gov (United States)

El-Ela, Fatma I Abo; Shany, S A S; El-Deen, Manal B; El-Banna, H A; El-Gendy, A A; Hendy, K; Tohamy, M A

2016-10-01

Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony.

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Metzger, Julia; Gast, Alana Christina; Schrimpf, Rahel; Rau, Janina; Eikelberg, Deborah; Beineke, Andreas; Hellige, Maren; Distl, Ottmar

2017-04-01

The Miniature Shetland pony represents a horse breed with an extremely small body size. Clinical examination of a dwarf Miniature Shetland pony revealed a lowered size at the withers, malformed skull and brachygnathia superior. Computed tomography (CT) showed a shortened maxilla and a cleft of the hard and soft palate which protruded into the nasal passage leading to breathing difficulties. Pathological examination confirmed these findings but did not reveal histopathological signs of premature ossification in limbs or cranial sutures. Whole-genome sequencing of this dwarf Miniature Shetland pony and comparative sequence analysis using 26 reference equids from NCBI Sequence Read Archive revealed three probably damaging missense variants which could be exclusively found in the affected foal. Validation of these three missense mutations in 159 control horses from different horse breeds and five donkeys revealed only the aggrecan (ACAN)-associated g.94370258G>C variant as homozygous wild-type in all control samples. The dwarf Miniature Shetland pony had the homozygous mutant genotype C/C of the ACAN:g.94370258G>C variant and the normal parents were heterozygous G/C. An unaffected full sib and 3/5 unaffected half-sibs were heterozygous G/C for the ACAN:g.94370258G>C variant. In summary, we could demonstrate a dwarf phenotype in a miniature pony breed perfectly associated with a missense mutation within the ACAN gene.

Peace journalism where there is no war. Conflict-sensitive reporting on urban violence and public security in Brazil and its potential role in conflict transformation

Directory of Open Access Journals (Sweden)

Joice Biazoto

2011-10-01

Full Text Available The absence of war in a country like Brazil does not mean peace for its population. High murder rates, police killings, and violent urban conflict (in the favelas and beyond are part of Brazilians’ daily lives. The national media helps construct the discourses of violence which contribute to maintain the status quo – but can the media play a positive role in the conflict and become a force for peace? In attempting to determine whether Peace Journalism is a useful tool for reporting about urban violence in Brazil, this qualitative case study analyzes a special series in Rio de Janeiro newspaper O Globo about a novel public security model in the city – the Pacifier Police Units (UPP – by employing adapted De-Escalation-Oriented Conflict Coverage (DEOCC criteria. The analysis reveals a combination of escalation and de-escalation elements in the series, and while this particular example does not prove to be conflict sensitive, the Peace Journalism framework itself shows great potential if implemented to improve coverage of urban violence in Brazil.

A potential target for organophosphate insecticides leading to spermatotoxicity.

Science.gov (United States)

Suzuki, Himiko; Tomizawa, Motohiro; Ito, Yuki; Abe, Keisuke; Noro, Yuki; Kamijima, Michihiro

2013-10-16

Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.

Diversity and Structure of Diazotrophic Communities in Mangrove Rhizosphere, Revealed by High-Throughput Sequencing.

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Zhang, Yanying; Yang, Qingsong; Ling, Juan; Van Nostrand, Joy D; Shi, Zhou; Zhou, Jizhong; Dong, Junde

2017-01-01

Diazotrophic communities make an essential contribution to the productivity through providing new nitrogen. However, knowledge of the roles that both mangrove tree species and geochemical parameters play in shaping mangove rhizosphere diazotrophic communities is still elusive. Here, a comprehensive examination of the diversity and structure of microbial communities in the rhizospheres of three mangrove species, Rhizophora apiculata , Avicennia marina , and Ceriops tagal , was undertaken using high - throughput sequencing of the 16S rRNA and nifH genes. Our results revealed a great diversity of both the total microbial composition and the diazotrophic composition specifically in the mangrove rhizosphere. Deltaproteobacteria and Gammaproteobacteria were both ubiquitous and dominant, comprising an average of 45.87 and 86.66% of total microbial and diazotrophic communities, respectively. Sulfate-reducing bacteria belonging to the Desulfobacteraceae and Desulfovibrionaceae were the dominant diazotrophs. Community statistical analyses suggested that both mangrove tree species and additional environmental variables played important roles in shaping total microbial and potential diazotroph communities in mangrove rhizospheres. In contrast to the total microbial community investigated by analysis of 16S rRNA gene sequences, most of the dominant diazotrophic groups identified by nifH gene sequences were significantly different among mangrove species. The dominant diazotrophs of the family Desulfobacteraceae were positively correlated with total phosphorus, but negatively correlated with the nitrogen to phosphorus ratio. The Pseudomonadaceae were positively correlated with the concentration of available potassium, suggesting that diazotrophs potentially play an important role in biogeochemical cycles, such as those of nitrogen, phosphorus, sulfur, and potassium, in the mangrove ecosystem.

Diversity and Structure of Diazotrophic Communities in Mangrove Rhizosphere, Revealed by High-Throughput Sequencing

Directory of Open Access Journals (Sweden)

Yanying Zhang

2017-10-01

Full Text Available Diazotrophic communities make an essential contribution to the productivity through providing new nitrogen. However, knowledge of the roles that both mangrove tree species and geochemical parameters play in shaping mangove rhizosphere diazotrophic communities is still elusive. Here, a comprehensive examination of the diversity and structure of microbial communities in the rhizospheres of three mangrove species, Rhizophora apiculata, Avicennia marina, and Ceriops tagal, was undertaken using high-throughput sequencing of the 16S rRNA and nifH genes. Our results revealed a great diversity of both the total microbial composition and the diazotrophic composition specifically in the mangrove rhizosphere. Deltaproteobacteria and Gammaproteobacteria were both ubiquitous and dominant, comprising an average of 45.87 and 86.66% of total microbial and diazotrophic communities, respectively. Sulfate-reducing bacteria belonging to the Desulfobacteraceae and Desulfovibrionaceae were the dominant diazotrophs. Community statistical analyses suggested that both mangrove tree species and additional environmental variables played important roles in shaping total microbial and potential diazotroph communities in mangrove rhizospheres. In contrast to the total microbial community investigated by analysis of 16S rRNA gene sequences, most of the dominant diazotrophic groups identified by nifH gene sequences were significantly different among mangrove species. The dominant diazotrophs of the family Desulfobacteraceae were positively correlated with total phosphorus, but negatively correlated with the nitrogen to phosphorus ratio. The Pseudomonadaceae were positively correlated with the concentration of available potassium, suggesting that diazotrophs potentially play an important role in biogeochemical cycles, such as those of nitrogen, phosphorus, sulfur, and potassium, in the mangrove ecosystem.

Prokaryotic caspase homologs: phylogenetic patterns and functional characteristics reveal considerable diversity.

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Johannes Asplund-Samuelsson

Full Text Available Caspases accomplish initiation and execution of apoptosis, a programmed cell death process specific to metazoans. The existence of prokaryotic caspase homologs, termed metacaspases, has been known for slightly more than a decade. Despite their potential connection to the evolution of programmed cell death in eukaryotes, the phylogenetic distribution and functions of these prokaryotic metacaspase sequences are largely uncharted, while a few experiments imply involvement in programmed cell death. Aiming at providing a more detailed picture of prokaryotic caspase homologs, we applied a computational approach based on Hidden Markov Model search profiles to identify and functionally characterize putative metacaspases in bacterial and archaeal genomes. Out of the total of 1463 analyzed genomes, merely 267 (18% were identified to contain putative metacaspases, but their taxonomic distribution included most prokaryotic phyla and a few archaea (Euryarchaeota. Metacaspases were particularly abundant in Alphaproteobacteria, Deltaproteobacteria and Cyanobacteria, which harbor many morphologically and developmentally complex organisms, and a distinct correlation was found between abundance and phenotypic complexity in Cyanobacteria. Notably, Bacillus subtilis and Escherichia coli, known to undergo genetically regulated autolysis, lacked metacaspases. Pfam domain architecture analysis combined with operon identification revealed rich and varied configurations among the metacaspase sequences. These imply roles in programmed cell death, but also e.g. in signaling, various enzymatic activities and protein modification. Together our data show a wide and scattered distribution of caspase homologs in prokaryotes with structurally and functionally diverse sub-groups, and with a potentially intriguing evolutionary role. These features will help delineate future characterizations of death pathways in prokaryotes.

Comparative genome and transcriptome analysis reveals distinctive surface characteristics and unique physiological potentials of Pseudomonas aeruginosa ATCC 27853

KAUST Repository

Cao, Huiluo

2017-06-12

virulence genes lecA, lasB, quorum sensing regulators LasI/R, and the type I, III and VI secretion systems were observed in the two strains.The complete genome sequence of P. aeruginosa ATCC 27853 reveals the comprehensive genetic background of the strain, and provides genetic basis for several interesting findings about the functions of surface associated proteins, prophages, and genomic islands. Comparative transcriptome analysis of P. aeruginosa ATCC 27853 and PAO1 revealed several classes of differentially expressed genes in the two strains, underlying the genetic and molecular details of several known and yet to be explored morphological and physiological potentials of P. aeruginosa ATCC 27853.

Set potential regulation reveals additional oxidation peaks of Geobacter sulfurreducens anodic biofilms

KAUST Repository

Zhu, Xiuping

2012-08-01

Higher current densities produced in microbial fuel cells and other bioelectrochemical systems are associated with the presence of various Geobacter species. A number of electron transfer components are involved in extracellular electron transfer by the model exoelectrogen, Geobacter sulfurreducens. It has previously been shown that 5 main oxidation peaks can be identified in cyclic voltammetry scans. It is shown here that 7 separate oxidation peaks emerged over relatively long periods of time when a larger range of set potentials was used to acclimate electroactive biofilms. The potentials of oxidation peaks obtained with G. sulfurreducens biofilms acclimated at 0.60 V (vs. Ag/AgCl) were different from those that developed at - 0.46 V, and both of their peaks were different from those obtained for biofilms incubated at - 0.30 V, 0 V, and 0.30 V. These results expand the known range of potentials for which G. sulfurreducens produces identifiable oxidation peaks that could be important for extracellular electron transfer. © 2012 Elsevier B.V.

A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

NARCIS (Netherlands)

Huidekoper, Hidde H.; Visser, Gepke; Ackermans, Mariëtte T.; Sauerwein, Hans P.; Wijburg, Frits A.

2010-01-01

A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-beta). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two

Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export.

Science.gov (United States)

Karijolich, John; Zhao, Yang; Alla, Ravi; Glaunsinger, Britt

2017-06-02

Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28 270 SINE loci, with ∼50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

From moderately severe to severe hypertriglyceridemia induced acute pancreatitis: circulating miRNAs play role as potential biomarkers.

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Fangmei An

Full Text Available The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP and severe (HTSAP, healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05 were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated, and 181a-5p (constantly downregulated (P<0.05. Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++, and insulin metabolism (P<0.001. miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG, total cholesterol (TC, and fast blood glucose (FBG, but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when

Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

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Bauer, Georg; Zarkovic, Neven

2015-04-01

Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Reading in the Development of Giftedness in the Context of Globalization and National Identity

Science.gov (United States)

Shastina, Elena; Shatunova, Olga; Borodina, Tatyana; Borisov, Anatoly; Maliy, Yury

2018-01-01

The article explores the cultural potential of reading as one of the factors in the development of children's giftedness. The role of the book as the bearer of culture in the process of preserving national identity is revealed. The authors of the article discover the growing importance of family reading in the process of a gifted person…

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

Science.gov (United States)

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-01-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

Graduate radiographers' expectations for role development - The potential impact of misalignment of expectation and valence on staff retention and service provision

International Nuclear Information System (INIS)

Williamson, Keren; Mundy, Lynn A.

2010-01-01

Purpose: The purpose of this study was to investigate the role development expectations of graduate radiographers with a view to predicting the potential impact of a misalignment of these expectations and valence on service delivery and staff retention. A final year cohort of radiography students completed a questionnaire designed to explore topics associated with role development opportunities. Method: Structured questionnaires, in the Likert scale format, utilised 20 attitude questions constructed to elicit information in relation to 3 main themes of investigation; expectation, valence and knowledge. Results: All participants (n = 37) stated an expectation for role development opportunities with 97.3% (n = 36) indicating that these expectations would be realised within 5 years of graduation and 75.7% (n = 28) within 2 years of graduation. A significant correlation between expectation for role development and job satisfaction was seen (p < 0.05). 81.1% (n = 30) of participants stated turnover intentions in order to meet their expectations. Conclusion: There is an expectation for role development opportunities for new graduates with a valence noted of the intrinsic reward of meeting these expectations. Expectation and valence are seen to be intrinsically linked with job satisfaction suggesting that misalignment of these would have a potentially negative impact on motivation and retention of the future radiography workforce demonstrating a positive correlation with withdrawal behaviours, including turnover intentions. In a relatively small professional group such as radiography the phenomenon of group cohesion may be strong suggesting that withdrawal behaviours may manifest as 'resignation in post', impacting on the quality of care and service provision for patients.

Anaerobic fungi (phylum Neocallimastigomycota): advances in understanding their taxonomy, life cycle, ecology, role and biotechnological potential.

Science.gov (United States)

Gruninger, Robert J; Puniya, Anil K; Callaghan, Tony M; Edwards, Joan E; Youssef, Noha; Dagar, Sumit S; Fliegerova, Katerina; Griffith, Gareth W; Forster, Robert; Tsang, Adrian; McAllister, Tim; Elshahed, Mostafa S

2014-10-01

Anaerobic fungi (phylum Neocallimastigomycota) inhabit the gastrointestinal tract of mammalian herbivores, where they play an important role in the degradation of plant material. The Neocallimastigomycota represent the earliest diverging lineage of the zoosporic fungi; however, understanding of the relationships of the different taxa (both genera and species) within this phylum is in need of revision. Issues exist with the current approaches used for their identification and classification, and recent evidence suggests the presence of several novel taxa (potential candidate genera) that remain to be characterised. The life cycle and role of anaerobic fungi has been well characterised in the rumen, but not elsewhere in the ruminant alimentary tract. Greater understanding of the 'resistant' phase(s) of their life cycle is needed, as is study of their role and significance in other herbivores. Biotechnological application of anaerobic fungi, and their highly active cellulolytic and hemi-cellulolytic enzymes, has been a rapidly increasing area of research and development in the last decade. The move towards understanding of anaerobic fungi using -omics based (genomic, transcriptomic and proteomic) approaches is starting to yield valuable insights into the unique cellular processes, evolutionary history, metabolic capabilities and adaptations that exist within the Neocallimastigomycota. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

Science.gov (United States)

Gallardo, Miguel; Barrio, Santiago; Fernandez, Marisol; Paradela, Alberto; Arenas, Alicia; Toldos, Oscar; Ayala, Rosa; Albizua, Enriqueta; Jimenez, Ana; Redondo, Santiago; Garcia-Martin, Rosa Maria; Gilsanz, Florinda; Albar, Juan Pablo; Martinez-Lopez, Joaquin

2013-11-19

JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

Microstructure and fracture toughness of irradiated stainless steel retrieved from the field: the potential role of radiation-induced clusters

International Nuclear Information System (INIS)

Chou, P.; Soneda, N.; Nishida, K.; Dohi, K.; Marquis, E.A.; Chen, Y.

2015-01-01

The microstructures of six material/fluence combinations of stainless steels retrieved from BWR components (top guide and control rods) have been examined by atom probe tomography; the irradiated microstructure had been already characterized by transmission electron microscopy (TEM). The fracture toughness of two material/fluence combinations had been previously measured. The aggregate results strongly suggest that radiation-induced clusters play a significant role in the degradation of fracture toughness that occurs at fluences below ∼ 13 dpa. Because TEM has not been able to consistently identify and quantify the nano-sized clusters in this fluence range, it has not highlighted the potential role of radiation-induced clusters. (authors)

Firewood, food and human niche construction: the potential role of Mesolithic hunter-gatherers in actively structuring Scotland's woodlands

Science.gov (United States)

Bishop, Rosie R.; Church, Mike J.; Rowley-Conwy, Peter A.

2015-01-01

Over the past few decades the potential role of Mesolithic hunter-gatherers in actively constructing their own niches, through the management of wild plants, has frequently been discussed. It is probable that Mesolithic hunter-gatherers systematically exploited specific woodland resources for food and fuel and influenced the 'natural' abundance or distribution of particular species within Mesolithic environments. Though there has been considerable discussion of the pollen evidence for potential small-scale human-woodland manipulation in Mesolithic Scotland, the archaeobotanical evidence for anthropogenic firewood and food selection has not been discussed in this context. This paper assesses the evidence for the active role of Mesolithic hunter-gatherer communities in systematically exploiting and managing woodlands for food and fuel in Scotland. While taphonomic factors may have impacted on the frequency of specific species in archaeobotanical assemblages, it is suggested that hunter-gatherers in Mesolithic Scotland were systematically using woodland plants, and in particular hazel and oak, for food and fuel. It is argued that the pollen evidence for woodland management is equivocal, but hints at the role of hunter-gatherers in shaping the structure of their environments, through the maintenance or creation of woodland clearings for settlement or as part of vegetation management strategies. It is proposed that Mesolithic hunter-gatherers may have actively contributed to niche construction and that the systematic use of hazel and oak as a fuel may reflect the deliberate pruning of hazel trees to increase nut-yields and the inadvertent - or perhaps deliberate - coppicing of hazel and oak during greenwood collection.

Dynamic energy budget modeling reveals the potential of future growth and calcification for the coccolithophore Emiliania huxleyi in an acidified ocean.

Science.gov (United States)

Muller, Erik B; Nisbet, Roger M

2014-06-01

Ocean acidification is likely to impact the calcification potential of marine organisms. In part due to the covarying nature of the ocean carbonate system components, including pH and CO2 and CO3(2-) levels, it remains largely unclear how each of these components may affect calcification rates quantitatively. We develop a process-based bioenergetic model that explains how several components of the ocean carbonate system collectively affect growth and calcification rates in Emiliania huxleyi, which plays a major role in marine primary production and biogeochemical carbon cycling. The model predicts that under the IPCC A2 emission scenario, its growth and calcification potential will have decreased by the end of the century, although those reductions are relatively modest. We anticipate that our model will be relevant for many other marine calcifying organisms, and that it can be used to improve our understanding of the impact of climate change on marine systems. © 2014 John Wiley & Sons Ltd.

A β-glucosidase hyper-production Trichoderma reesei mutant reveals a potential role of cel3D in cellulase production.

Science.gov (United States)

Li, Chengcheng; Lin, Fengming; Li, Yizhen; Wei, Wei; Wang, Hongyin; Qin, Lei; Zhou, Zhihua; Li, Bingzhi; Wu, Fugen; Chen, Zhan

2016-09-01

production, high cellulase production within a shorter time and a better resistance to carbon catabolite repression. Disruption of β-glucosidase cel3D in TRB1 was identified, which might contribute to the superiority of TRB1 over RUT-C30 and might play a role in the cellulase production. These results laid a foundation for future investigations to further improve cellulase enzymatic efficiency and reduce cost for T. reesei cellulase production.

Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis.

Science.gov (United States)

Zeng, Chunwei; Wen, Bo; Hou, Guixue; Lei, Li; Mei, Zhanlong; Jia, Xuekun; Chen, Xiaomin; Zhu, Wu; Li, Jie; Kuang, Yehong; Zeng, Weiqi; Su, Juan; Liu, Siqi; Peng, Cong; Chen, Xiang

2017-10-01

Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene-environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis. © The Author 2017. Published by Oxford University Press.

Calcium sensing receptor expression in ovine amniotic fluid mesenchymal stem cells and the potential role of R-568 during osteogenic differentiation.

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Pamela Di Tomo

Full Text Available Amniotic fluid-derived stem (AFS cells have been identified as a promising source for cell therapy applications in bone traumatic and degenerative damage. Calcium Sensing Receptor (CaSR, a G protein-coupled receptor able to bind calcium ions, plays a physiological role in regulating bone metabolism. It is expressed in different kinds of cells, as well as in some stem cells. The bone CaSR could potentially be targeted by allosteric modulators, in particular by agonists such as calcimimetic R-568, which may potentially be helpful for the treatment of bone disease. The aim of our study was first to investigate the presence of CaSR in ovine Amniotic Fluid Mesenchymal Stem Cells (oAFMSCs and then the potential role of calcimimetics in in vitro osteogenesis. oAFMSCs were isolated, characterized and analyzed to examine the possible presence of CaSR by western blotting and flow cytometry analysis. Once we had demonstrated CaSR expression, we worked out that 1 µM R-568 was the optimal and effective concentration by cell viability test (MTT, cell number, Alkaline Phosphatase (ALP and Alizarin Red S (ARS assays. Interestingly, we observed that basal diffuse CaSR expression in oAFMSCs increased at the membrane when cells were treated with R-568 (1 µM, potentially resulting in activation of the receptor. This was associated with significantly increased cell mineralization (ALP and ARS staining and augmented intracellular calcium and Inositol trisphosphate (IP3 levels, thus demonstrating a potential role for calcimimetics during osteogenic differentiation. Calhex-231, a CaSR allosteric inhibitor, totally reversed R-568 induced mineralization. Taken together, our results demonstrate for the first time that CaSR is expressed in oAFMSCs and that calcimimetic R-568, possibly through CaSR activation, can significantly improve the osteogenic process. Hence, our study may provide useful information on the mechanisms regulating osteogenesis in oAFMSCs, perhaps

Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance.

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Lindsey, J C; Kawauchi, D; Schwalbe, E C; Solecki, D J; Selby, M P; McKinnon, P J; Olson, J M; Hayden, J T; Grundy, R G; Ellison, D W; Williamson, D; Bailey, S; Roussel, M F; Clifford, S C

2015-09-03

The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma.

Comparative genomics of four closely related Clostridium perfringens bacteriophages reveals variable evolution among core genes with therapeutic potential

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Siragusa Gregory R

2011-06-01

Full Text Available Abstract Background Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen. Results Phage whole-genome tetra-nucleotide signatures and proteomic tree topologies correlated closely with host phylogeny. Comparisons of our phage genomes to 26 others revealed three shared COGs; of particular interest within this core genome was an endolysin (PF01520, an N-acetylmuramoyl-L-alanine amidase and a holin (PF04531. Comparative analyses of the evolutionary history and genomic context of these common phage proteins revealed two important results: 1 strongly significant host-specific sequence variation within the endolysin, and 2 a protein domain architecture apparently unique to our phage genomes in which the endolysin is located upstream of its associated holin. Endolysin sequences from our phages were one of two very distinct genotypes distinguished by variability within the putative enzymatically-active domain. The shared or core genome was comprised of genes with multiple sequence types belonging to five pfam families, and genes belonging to 12 pfam families, including the holin genes, which were nearly identical. Conclusions Significant genomic diversity exists even among closely-related bacteriophages. Holins and endolysins represent conserved functions across divergent phage genomes and, as we demonstrate here, endolysins can have significant variability and host-specificity even among closely-related genomes. Endolysins in our phage genomes may be subject to different selective pressures than the rest of the genome. These findings may have important implications for potential biotechnological applications of phage gene products.

The Role of Auditory Evoked Potentials in the Context of Cochlear Implant Provision.

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Hoth, Sebastian; Dziemba, Oliver Christian

2017-12-01

: Auditory evoked potentials (AEP) are highly demanded during the whole process of equipping patients with cochlear implants (CI). They play an essential role in preoperative diagnostics, intraoperative testing, and postoperative monitoring of auditory performance and success. The versatility of AEP's is essentially enhanced by their property to be evokable by acoustic as well as electric stimuli. Thus, the electric responses of the auditory system following acoustic stimulation and recorded by the conventional surface technique as well as by transtympanic derivation from the promontory (Electrocochleography [ECochG]) are used for the quantitative determination of hearing loss and, additionally, electrically evoked compound actions potentials (ECAP) can be recorded with the intracochlear electrodes of the implant just adjacent to the stimulation electrode to check the functional integrity of the device and its coupling to the auditory system. The profile of ECAP thresholds is used as basis for speech processor fitting, the spread of excitation (SOE) allows the identification of electrode mislocations such as array foldover, and recovery functions may serve to optimize stimulus pulse rate. These techniques as well as those relying on scalp surface activity originating in the brainstem or the auditory cortex accompany the CI recipient during its whole life span and they offer valuable insights into functioning and possible adverse effects of the CI for clinical and scientific purposes.

Proteome profiling of neuroblastoma-derived exosomes reveal the expression of proteins potentially involved in tumor progression.

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Danilo Marimpietri

Full Text Available Neuroblastoma (NB is the most common extracranial solid tumor in childhood, with grim prognosis in a half of patients. Exosomes are nanometer-sized membrane vesicles derived from the multivesicular bodies (MVBs of the endocytic pathway and released by normal and neoplastic cells. Tumor-derived exosomes have been shown in different model systems to carry molecules that promote cancer growth and dissemination. In this respect, we have here performed the first characterization and proteomic analysis of exosomes isolated from human NB cell lines by filtration and ultracentrifugation. Electron microscopy demonstrated that NB-derived exosomes exhibited the characteristic cup-shaped morphology. Dynamic light scattering studies showed a bell-shaped curve and a polydispersity factor consistent with those of exosomes. Zeta potential values suggested a good nanoparticle stability. We performed proteomic analysis of NB-derived exosomes by two dimension liquid chromatography separation and mass spectrometry analyses using the multidimensional protein identification technology strategy. We found that the large majority of the proteins identified in NB derived exosomes are present in Exocarta database including tetraspanins, fibronectin, heat shock proteins, MVB proteins, cytoskeleton-related proteins, prominin-1 (CD133, basigin (CD147 and B7-H3 (CD276. Expression of the CD9, CD63 and CD81 tetraspanins, fibronectin, CD133, CD147 and CD276 was validated by flow cytometry. Noteworthy, flow cytometric analysis showed that NB-derived exosomes expressed the GD2 disialoganglioside, the most specific marker of NB. In conclusion, this study shows that NB-derived exosomes express a discrete set of molecules involved in defense response, cell differentiation, cell proliferation and regulation of other important biological process. Thus, NB-derived exosomes may play an important role in the modulation of tumor microenvironment and represent potential tumor biomarkers.

Mexican American Adolescents’ Gender Role Attitude Development: The Role of Adolescents’ Gender and Nativity and Parents’ Gender Role Attitudes

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Updegraff, Kimberly A.; McHale, Susan M.; Zeiders, Katharine H.; Umaña-Taylor, Adriana J.; Perez-Brena, Norma J.; Wheeler, Lorey A.; Rodríguez De Jesús, Sue A.

2014-01-01

Gender development has long term implications for education and career endeavors and family formation behaviors, but we know very little about the role of sociocultural factors in developmental and individual differences. In this study, we investigated one domain of gender development, gender role attitudes, in Mexican American adolescents (N = 246; 51% female), using four phases of longitudinal data across eight years. Data were collected when adolescents averaged 12.51 years (SD = 0.58), 14.64 years (SD = 0.59), 17.72 years (SD = 0.57), and 19.60 years of age (SD = 0.66). Mothers’ and fathers’ gender role attitudes also were assessed in Phases 1, 3, and 4. Findings revealed that gender attitude development varied as a function of the interaction between adolescents’ nativity and gender. Among Mexico-born adolescents, females exhibited significant declines in traditional attitudes from early to late adolescence, but males’ attitudes were stable over time. U.S.-born females and males, in contrast, did not differ in their gender attitude trajectories. Examining the links between mothers’, fathers’, and adolescents’ gender role attitudes revealed within-person associations between mothers’ and adolescents’ gender role attitudes: on occasions when mothers reported more traditional attitudes relative to their own cross-time average, adolescents also reported more traditional attitudes than usual. In addition, fathers’ more traditional gender role attitudes were associated with daughters’, but not sons’, more traditional gender role attitudes at the between-person level. The discussion focuses on the interpretation of Mexican American adolescents’ gender role attitude development from a cultural ecological perspective. PMID:24777649

Interspecific proteomic comparisons reveal ash phloem genes potentially involved in constitutive resistance to the emerald ash borer.

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Whitehill, Justin G A; Popova-Butler, Alexandra; Green-Church, Kari B; Koch, Jennifer L; Herms, Daniel A; Bonello, Pierluigi

2011-01-01

The emerald ash borer (Agrilus planipennis) is an invasive wood-boring beetle that has killed millions of ash trees since its accidental introduction to North America. All North American ash species (Fraxinus spp.) that emerald ash borer has encountered so far are susceptible, while an Asian species, Manchurian ash (F. mandshurica), which shares an evolutionary history with emerald ash borer, is resistant. Phylogenetic evidence places North American black ash (F. nigra) and Manchurian ash in the same clade and section, yet black ash is highly susceptible to the emerald ash borer. This contrast provides an opportunity to compare the genetic traits of the two species and identify those with a potential role in defense/resistance. We used Difference Gel Electrophoresis (DIGE) to compare the phloem proteomes of resistant Manchurian to susceptible black, green, and white ash. Differentially expressed proteins associated with the resistant Manchurian ash when compared to the susceptible ash species were identified using nano-LC-MS/MS and putative identities assigned. Proteomic differences were strongly associated with the phylogenetic relationships among the four species. Proteins identified in Manchurian ash potentially associated with its resistance to emerald ash borer include a PR-10 protein, an aspartic protease, a phenylcoumaran benzylic ether reductase (PCBER), and a thylakoid-bound ascorbate peroxidase. Discovery of resistance-related proteins in Asian species will inform approaches in which resistance genes can be introgressed into North American ash species. The generation of resistant North American ash genotypes can be used in forest ecosystem restoration and urban plantings following the wake of the emerald ash borer invasion.

Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

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Lee, Jieun; Wolfgang, Michael J

2012-10-25

Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

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Lee Jieun

2012-10-01

Full Text Available Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. Results In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT and CPT1c knockout (KO mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Conclusions Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

Micro-RNAs and their roles in eye disorders.

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Raghunath, Azhwar; Perumal, Ekambaram

2015-01-01

Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders. © 2015 S. Karger AG, Basel.

Bat flies (Diptera: Nycteribiidae and Streblidae) infesting cave-dwelling bats in Gabon: diversity, dynamics and potential role in Polychromophilus melanipherus transmission.

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Obame-Nkoghe, Judicaël; Rahola, Nil; Bourgarel, Mathieu; Yangari, Patrick; Prugnolle, Franck; Maganga, Gael Darren; Leroy, Eric-Maurice; Fontenille, Didier; Ayala, Diego; Paupy, Christophe

2016-06-10

Evidence of haemosporidian infections in bats and bat flies has motivated a growing interest in characterizing their transmission cycles. In Gabon (Central Africa), many caves house massive colonies of bats that are known hosts of Polychromophilus Dionisi parasites, presumably transmitted by blood-sucking bat flies. However, the role of bat flies in bat malaria transmission remains under-documented. An entomological survey was carried out in four caves in Gabon to investigate bat fly diversity, infestation rates and host preferences and to determine their role in Polychromophilus parasite transmission. Bat flies were sampled for 2-4 consecutive nights each month from February to April 2011 (Faucon and Zadie caves) and from May 2012 to April 2013 (Kessipoughou and Djibilong caves). Bat flies isolated from the fur of each captured bat were morphologically identified and screened for infection by haemosporidian parasites using primers targeting the mitochondrial cytochrome b gene. Among the 1,154 bats captured and identified as Miniopterus inflatus Thomas (n = 354), Hipposideros caffer Sundevall complex (n = 285), Hipposideros gigas Wagner (n = 317), Rousettus aegyptiacus Geoffroy (n = 157, and Coleura afra Peters (n = 41), 439 (38.0 %) were infested by bat flies. The 1,063 bat flies recovered from bats belonged to five taxa: Nycteribia schmidlii scotti Falcoz, Eucampsipoda africana Theodor, Penicillidia fulvida Bigot, Brachytarsina allaudi Falcoz and Raymondia huberi Frauenfeld group. The mean infestation rate varied significantly according to the bat species (ANOVA, F (4,75) = 13.15, P bat fly species and host bat species was observed. Polychromophilus melanipherus Dionisi was mainly detected in N. s. scotti and P. fulvida and less frequently in E. africana, R. huberi group and B. allaudi bat flies. These results suggest that N. s. scotti and P. fulvida could potentially be involved in P. melanipherus transmission among cave-dwelling bats

Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

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Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

2016-10-26

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

Terrestrial Macrofungal Diversity from the Tropical Dry Evergreen Biome of Southern India and Its Potential Role in Aerobiology.

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Priyamvada, Hema; Akila, M; Singh, Raj Kamal; Ravikrishna, R; Verma, R S; Philip, Ligy; Marathe, R R; Sahu, L K; Sudheer, K P; Gunthe, S S

2017-01-01

Macrofungi have long been investigated for various scientific purposes including their food and medicinal characteristics. Their role in aerobiology as a fraction of the primary biological aerosol particles (PBAPs), however, has been poorly studied. In this study, we present a source of macrofungi with two different but interdependent objectives: (i) to characterize the macrofungi from a tropical dry evergreen biome in southern India using advanced molecular techniques to enrich the database from this region, and (ii) to assess whether identified species of macrofungi are a potential source of atmospheric PBAPs. From the DNA analysis, we report the diversity of the terrestrial macrofungi from a tropical dry evergreen biome robustly supported by the statistical analyses for diversity conclusions. A total of 113 macrofungal species belonging to 54 genera and 23 families were recorded, with Basidiomycota and Ascomycota constituting 96% and 4% of the species, respectively. The highest species richness was found in the family Agaricaceae (25.3%) followed by Polyporaceae (15.3%) and Marasmiaceae (10.8%). The difference in the distribution of commonly observed macrofungal families over this location was compared with other locations in India (Karnataka, Kerala, Maharashtra, and West Bengal) using two statistical tests. The distributions of the terrestrial macrofungi were distinctly different in each ecosystem. We further attempted to demonstrate the potential role of terrestrial macrofungi as a source of PBAPs in ambient air. In our opinion, the findings from this ecosystem of India will enhance our understanding of the distribution, diversity, ecology, and biological prospects of terrestrial macrofungi as well as their potential to contribute to airborne fungal aerosols.

Interparticle potential of 10 nanometer titanium nanoparticles in liquid sodium: Theoretical approach

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Kim, Soo Jae; Park, Gun Yeop; Park, Hyun Sun; Baek, Je Hyun [POSTECH, Pohang (Korea, Republic of); Kim, Moo Hwan [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2015-10-15

A suspension of titanium nanoparticles (Ti NPs) in liquid sodium (Na) has been proposed as a method to mitigate the violent sodium-water reaction (SWR). The interparticle potential between Ti NPs in liquid Na may play a significant role in the agglomeration of NPs on the reaction surface and in the bulk liquid Na, since the potential contributes to a reduction in the long-term dispersion stability. For the effective control of the SWR with NPs, a physical understanding of the molecular dynamics of NPs in liquid Na is key. Therefore in this study, the nonretarded Van der Waals model and the solvation potential model are employed to analyze the interparticle potential. The ab initio calculation reveals that a strong repulsive force driven by the solvation potential exceeds the interparticle attraction and predicts the agglomeration energy required for two 10-nm Ti NPs to be 4 x 10{sup -17} J. The collision theory suggests that Ti NPs can be effective suppressors of the SWR due to the high energy barrier that prevents significant agglomeration of Ti NPs in quiescent liquid Na.

A Neuropsychological Approach to Understanding Risk-Taking for Potential Gains and Losses

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Levin, Irwin P.; Xue, Gui; Weller, Joshua A.; Reimann, Martin; Lauriola, Marco; Bechara, Antoine

2012-01-01

Affective neuroscience has helped guide research and theory development in judgment and decision-making by revealing the role of emotional processes in choice behavior, especially when risk is involved. Evidence is emerging that qualitatively and quantitatively different processes may be involved in risky decision-making for gains and losses. We start by reviewing behavioral work by Kahneman and Tversky (1979) and others, which shows that risk-taking differs for potential gains and potential losses. We then turn to the literature in decision neuroscience to support the gain versus loss distinction. Relying in part on data from a new task that separates risky decision-making for gains and losses, we test a neural model that assigns unique mechanisms for risky decision-making involving potential losses. Included are studies using patients with lesions to brain areas specified as important in the model and studies with healthy individuals whose brains are scanned to reveal activation in these and other areas during risky decision-making. In some cases, there is evidence that gains and losses are processed in different regions of the brain, while in other cases the same region appears to process risk in a different manner for gains and losses. At a more general level, we provide strong support for the notion that decisions involving risk-taking for gains and decisions involving risk-taking for losses represent different psychological processes. At a deeper level, we present mounting evidence that different neural structures play different roles in guiding risky choices in these different domains. Some structures are differentially activated by risky gains and risky losses while others respond uniquely in one domain or the other. Taken together, these studies support a clear functional dissociation between risk-taking for gains and risk-taking for losses, and further dissociation at the neural level. PMID:22347161

Porphyromonas gingivalis-mediated shedding of extracellular matrix metalloproteinase inducer (EMMPRIN) by oral epithelial cells: a potential role in inflammatory periodontal disease.

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Feldman, Mark; La, Vu Dang; Lombardo Bedran, Telma Blanca; Palomari Spolidorio, Denise Madalena; Grenier, Daniel

2011-12-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) or CD147 is a transmembrane glycoprotein expressed by various cell types, including oral epithelial cells. Recent studies have brought evidence that EMMPRIN plays a role in periodontitis. In the present study, we investigated the effect of Porphyromonas gingivalis, a major pathogen in chronic periodontitis, on the shedding of membrane-anchored EMMPRIN and on the expression of the EMMPRIN gene by oral epithelial cells. A potential contribution of shed EMMPRIN to the inflammatory process of periodontitis was analyzed by evaluating the effect of recombinant EMMPRIN on cytokine and matrix metalloproteinase (MMP) secretion by human gingival fibroblasts. ELISA and immunofluorescence analyses revealed that P. gingivalis mediated the shedding of epithelial cell-surface EMMPRIN in a dose- and time-dependent manner. Cysteine proteinase (gingipain)-deficient P. gingivalis mutants were used to demonstrate that both Arg- and Lys-gingipain activities are involved in EMMPRIN shedding. Real-time PCR showed that P. gingivalis had no significant effect on the expression of the EMMPRIN gene in epithelial cells. Recombinant EMMPRIN induced the secretion of IL-6 and MMP-3 by gingival fibroblasts, a phenomenon that appears to involve mitogen activated protein kinases. The present study brought to light a new mechanism by which P. gingivalis can promote the inflammatory response during periodontitis. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis.

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Laggner, Ute; Di Meglio, Paola; Perera, Gayathri K; Hundhausen, Christian; Lacy, Katie E; Ali, Niwa; Smith, Catherine H; Hayday, Adrian C; Nickoloff, Brian J; Nestle, Frank O

2011-09-01

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF-α- and IFN-γ-dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, these data indicate redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.

Whole transcriptome analysis reveals potential novel mechanisms of low-level linezolid resistance in Enterococcus faecalis.

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Hua, Ruoyi; Xia, Yun; Wu, Wenyao; Yan, Jia; Yang, Mi

2018-03-20

Linezolid is an oxazolidinone antibiotic commonly used to treat serious infections caused by vancomycin-resistant enterococcus. Recently, low-level linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the resistant mechanisms remain undefined. Whole-transcriptome profiling was performed on an E. faecalis strain P10748 with low-level linezolid resistance in comparison with a linezolid-susceptible strain 3138 and the standard control strain ATCC29212. The functions of differentially expressed genes (DEGs) were predicted, with some DEGs potentially involved in drug resistance were validated by PCR and quantitative PCR (qPCR). RNA-Seq on three E. faecalis strains generated 1920 unigenes, with 98% of them assigned to various function groups. A total of 150 DEGs were identified in the linezolid resistant strain P10748 compared to the linezolid susceptible strains 3138 and ATCC29212. Functional analysis indicated a significant transcriptomic shift to membrane transportation and biofilm formation in strain P10748, with three significantly up-regulated DEGs predicted to be associated with drug resistance through active efflux pumps and biofilm formation. The existence of these three DEGs was further confirmed by PCR and qPCR. The significant upregulation of genes associated with efflux pumps and biofilm formation in the linezolid resistant strain suggests their roles in low-level resistance to linezolid in E. faecalis. Copyright © 2018. Published by Elsevier B.V.

The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs.

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Thielke, Lauren E; Udell, Monique A R

2017-02-01

The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature. © 2015 Cambridge Philosophical Society.

Flotation of algae for water reuse and biomass production: role of zeta potential and surfactant to separate algal particles.

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Kwak, Dong-Heui; Kim, Mi-Sug

2015-01-01

The effect of chemical coagulation and biological auto-flocculation relative to zeta potential was examined to compare flotation and sedimentation separation processes for algae harvesting. Experiments revealed that microalgae separation is related to auto-flocculation of Anabaena spp. and requires chemical coagulation for the whole period of microalgae cultivation. In addition, microalgae separation characteristics which are associated with surfactants demonstrated optimal microalgae cultivation time and separation efficiency of dissolved CO2 flotation (DCF) as an alternative to dissolved air flotation (DAF). Microalgae were significantly separated in response to anionic surfactant rather than cationic surfactant as a function of bubble size and zeta potential. DAF and DCF both showed slightly efficient flotation; however, application of anionic surfactant was required when using DCF.

Emerging Insights on Brazilian Pepper Tree (Schinus terebinthifolius) Invasion: The Potential Role of Soil Microorganisms

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Dawkins, Karim; Esiobu, Nwadiuto

2016-01-01

Invasive plant species constitute a major ecological and economic problem worldwide, often distorting trophic levels and ecosystem balance. Numerous studies implicate factors ranging from environmental plasticity, competition for nutrient and space, and allelopathy in the success of invasive species in general. The Brazilian Pepper tree (BP) was introduced to the United States in the 1800s and has since become a category one invasive plant in Florida. It has aggressively spread to about 3000 km2 of terrestrial surface, fueled in part by the prevalence of the hybrid genotypes and environmental perturbations. It displays some of the well-established invasive mechanisms but there is a serious dearth of knowledge on the plant–microbe–soil interactions and whether the rhizobiome plays any roles in the displacement of native flora and the range expansion of BP. Several control measures, including chemical, mechanical, and biological antagonism have been used with limited success while restoration of natives in soils from which BP was removed has proved problematic partly due to a poorly understood phenomenon described as the “BP legacy effect.” Emerging evidence suggests that allelopathy, selective recruitment of beneficial soil microbes, disruption of microbial community structure and alteration of nutrient cycling, exhibited by many other invasive plant species may also be involved in the case of BP. This brief review discusses the well-established BP invasion mechanisms and highlights the current understanding of the molecular, below-ground processes. It also points out the gaps in studies on the potential role of microbial interactions in the success of BP invasion. These hitherto poorly studied mechanisms could further explain the aggressive spread of BP and could potentially contribute significantly to effective control measures and enable appropriate strategies for restoring native plants. The review advocates for the use of cutting-edge techniques in

Genome-Wide Analysis of Secondary Metabolite Gene Clusters in Ophiostoma ulmi and Ophiostoma novo-ulmi Reveals a Fujikurin-Like Gene Cluster with a Putative Role in Infection

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Nicolau Sbaraini

2017-06-01

Full Text Available The emergence of new microbial pathogens can result in destructive outbreaks, since their hosts have limited resistance and pathogens may be excessively aggressive. Described as the major ecological incident of the twentieth century, Dutch elm disease, caused by ascomycete fungi from the Ophiostoma genus, has caused a significant decline in elm tree populations (Ulmus sp. in North America and Europe. Genome sequencing of the two main causative agents of Dutch elm disease (Ophiostoma ulmi and Ophiostoma novo-ulmi, along with closely related species with different lifestyles, allows for unique comparisons to be made to identify how pathogens and virulence determinants have emerged. Among several established virulence determinants, secondary metabolites (SMs have been suggested to play significant roles during phytopathogen infection. Interestingly, the secondary metabolism of Dutch elm pathogens remains almost unexplored, and little is known about how SM biosynthetic genes are organized in these species. To better understand the metabolic potential of O. ulmi and O. novo-ulmi, we performed a deep survey and description of SM biosynthetic gene clusters (BGCs in these species and assessed their conservation among eight species from the Ophiostomataceae family. Among 19 identified BGCs, a fujikurin-like gene cluster (OpPKS8 was unique to Dutch elm pathogens. Phylogenetic analysis revealed that orthologs for this gene cluster are widespread among phytopathogens and plant-associated fungi, suggesting that OpPKS8 may have been horizontally acquired by the Ophiostoma genus. Moreover, the detailed identification of several BGCs paves the way for future in-depth research and supports the potential impact of secondary metabolism on Ophiostoma genus’ lifestyle.

Roles of Communication Problems and Communication Strategies on Resident-Related Role Demand and Role Satisfaction.

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Savundranayagam, Marie Y; Lee, Christopher

2017-03-01

This study investigated the impact of dementia-related communication difficulties and communication strategies used by staff on resident-related indicators of role demand and role satisfaction. Formal/paid long-term care staff caregivers (N = 109) of residents with dementia completed questionnaires on dementia-related communication difficulties, communication strategies, role demand (ie, residents make unreasonable demands), and role satisfaction (measured by relationship closeness and influence over residents). Three types of communication strategies were included: (a) effective repair strategies, (b) completing actions by oneself, and (c) tuning out or ignoring the resident. Analyses using structural equation modeling revealed that communication problems were positively linked with role demand. Repair strategies were positively linked with relationship closeness and influence over residents. Completing actions by oneself was positively linked to role demand and influence over residents, whereas tuning out was negatively linked with influence over residents. The findings underscore that effective caregiver communication skills are essential in enhancing staff-resident relationships.

Testosterone in the brain: neuroimaging findings and the potential role for neuropsychopharmacology.

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Höfer, Peter; Lanzenberger, Rupert; Kasper, Siegfried

2013-02-01

Testosterone plays a substantial role in a number of physiological processes in the brain. It is able to modulate the expression of certain genes by binding to androgen receptors. Acting via neurotransmitter receptors, testosterone shows the potential to mediate a non-genomic so-called "neuroactive effect". Various neurotransmitter systems are also influenced by the aromatized form of testosterone, estradiol. The following article summarizes the findings of preclinical and clinical neuroimaging studies including structural and functional magnetic resonance imaging (MRI/fMRI), voxel based morphometry (VBM), as well as pharmacological fMRI (phfMRI) and positron emission tomography (PET) regarding the effects of testosterone on the human brain. The impact of testosterone on the pathogenesis of psychiatric disorders and on sex-related prevalence differences have been supported by a wide range of clinical studies. An antidepressant effect of testosterone can be implicitly explained by its effects on the limbic system--especially amygdala, a major target in the treatment of depression--solidly demonstrated by a large body of neuroimaging findings. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Kaempferol glycosides from Lobularia maritima and their potential role in plant interactions.

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Fiorentino, Antonio; Ricci, Andreina; D'Abrosca, Brigida; Golino, Annunziata; Izzo, Angelina; Pascarella, Maria Teresa; Piccolella, Simona; Esposito, Assunta

2009-02-01

Six kaempferol glycosides, four of them characterized for the first time, were isolated from the leaf extract of Lobularia maritima. The structural elucidation was performed by a combined approach using Electrospray-Ionization Triple-Quadrupole Mass-Spectrometric (ESI/TQ/MS) techniques, and 1D- and 2D-NMR experiments (1H, 13C, DEPT, DQ-COSY, TOCSY, ROESY, NOESY, HSQC, HMBC, and HSQC-TOCSY). The isolated kaempferol derivatives have different disaccharide substituents at C(3) and four of them have a rhamnose unit at C(7). To evaluate their potential allelopathic role within the herbaceous plant community, the compounds, as well as the aglycone obtained from enzymatic hydrolysis, have been tested in vitro on three coexisting plant species, Dactylis hispanica, Petrorhagia velutina, and Phleum subulatum. The results obtained allow us to hypothesize that the type of the sugar modulates the biological response. The bioassay data, analyzed by a multivariate approach, and grouping the compounds on the basis of the number of sugar units and the nature of carbohydrates present in the disaccharide moiety, indicate a structure-activity relationship.

Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions

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Cristina Bartocci

2014-05-01

Full Text Available When telomeres become critically short, DNA damage response factors are recruited at chromosome ends, initiating a cellular response to DNA damage. We performed proteomic isolation of chromatin fragments (PICh in order to define changes in chromatin composition that occur upon onset of acute telomere dysfunction triggered by depletion of the telomere-associated factor TRF2. This unbiased purification of telomere-associated proteins in functional or dysfunctional conditions revealed the dynamic changes in chromatin composition that take place at telomeres upon DNA damage induction. On the basis of our results, we describe a critical role for the polycomb group protein Ring1b in nonhomologous end-joining (NHEJ-mediated end-to-end chromosome fusions. We show that cells with reduced levels of Ring1b have a reduced ability to repair uncapped telomeric chromatin. Our data represent an unbiased isolation of chromatin undergoing DNA damage and are a valuable resource to map the changes in chromatin composition in response to DNA damage activation.

Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change.

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Deanna N Edwards

Full Text Available Recent research indicates that hundreds of thousands of G-rich sequences within the human genome have the potential to form secondary structures known as G-quadruplexes. Telomeric regions, consisting of long arrays of TTAGGG/AATCCC repeats, are among the most likely areas in which these structures might form. Since G-quadruplexes assemble from certain G-rich single-stranded sequences, they might arise when duplex DNA is unwound such as during replication. Coincidentally, these bulky structures when present in the DNA template might also hinder the action of DNA polymerases. In this study, single-stranded telomeric templates with the potential to form G-quadruplexes were examined for their effects on a variety of replicative and translesion DNA polymerases from humans and lower organisms. Our results demonstrate that single-stranded templates containing four telomeric GGG runs fold into intramolecular G-quadruplex structures. These intramolecular G quadruplexes are somewhat dynamic in nature and stabilized by increasing KCl concentrations and decreasing temperatures. Furthermore, the presence of these intramolecular G-quadruplexes in the template dramatically inhibits DNA synthesis by various DNA polymerases, including the human polymerase δ employed during lagging strand replication of G-rich telomeric strands and several human translesion DNA polymerases potentially recruited to sites of replication blockage. Notably, misincorporation of nucleotides is observed when certain translesion polymerases are employed on substrates containing intramolecular G-quadruplexes, as is extension of the resulting mismatched base pairs upon dynamic unfolding of this secondary structure. These findings reveal the potential for blockage of DNA replication and genetic changes related to sequences capable of forming intramolecular G-quadruplexes.

ISC1-dependent metabolic adaptation reveals an indispensable role for mitochondria in induction of nuclear genes during the diauxic shift in Saccharomyces cerevisiae.

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Kitagaki, Hiroshi; Cowart, L Ashley; Matmati, Nabil; Montefusco, David; Gandy, Jason; de Avalos, Silvia Vaena; Novgorodov, Sergei A; Zheng, Jim; Obeid, Lina M; Hannun, Yusuf A

2009-04-17

Growth of Saccharomyces cerevisiae following glucose depletion (the diauxic shift) depends on a profound metabolic adaptation accompanied by a global reprogramming of gene expression. In this study, we provide evidence for a heretofore unsuspected role for Isc1p in mediating this reprogramming. Initial studies revealed that yeast cells deleted in ISC1, the gene encoding inositol sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic phase, showed defective aerobic respiration in the post-diauxic phase but retained normal intrinsic mitochondrial functions, including intact mitochondrial DNA, normal oxygen consumption, and normal mitochondrial polarization. Microarray analysis revealed that the Deltaisc1 strain failed to up-regulate genes required for nonfermentable carbon source metabolism during the diauxic shift, thus suggesting a mechanism for the defective supply of respiratory substrates into mitochondria in the post-diauxic phase. This defect in regulating nuclear gene induction in response to a defect in a mitochondrial enzyme raised the possibility that mitochondria may initiate diauxic shift-associated regulation of nucleus-encoded genes. This was established by demonstrating that in respiratory-deficient petite cells these genes failed to be up-regulated across the diauxic shift in a manner similar to the Deltaisc1 strain. Isc1p- and mitochondrial function-dependent genes significantly overlapped with Adr1p-, Snf1p-, and Cat8p-dependent genes, suggesting some functional link among these factors. However, the retrograde response was not activated in Deltaisc1, suggesting that the response of Deltaisc1 cannot be simply attributed to mitochondrial dysfunction. These results suggest a novel role for Isc1p in allowing the reprogramming of gene expression during the transition from anaerobic to aerobic metabolism.

Negative Correlation between miR-200c and Decorin Plays an Important Role in the Pathogenesis of Colorectal Carcinoma

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Ren-Yi Tang

2017-01-01

Full Text Available Aim. To demonstrate the regulatory role of miRNA in colorectal carcinoma (CRC and reveal the transcript markers that may be associated with CRC clinical outcomes. Method. Herein, we analyzed both mRNA and miRNA gene expression profiles of 255 CRC tumor samples from The Cancer Genome Atlas project to reveal the regulatory association between miRNA and mRNA. Also, the potential role of gene coexpression network in CRC has been explored. Results. The negative correlation between miR-200c and DCN (Decorin was calculated in CRC, indicating that DCN could be a potential target of miR-200c. Clinical features indicated that colon polyp history and overall survival were significantly related to the expression level of miR-200c. Three coexpression networks have been constructed, and genes involved in the networks are related to cell cycle, NOTCH, and mTOR signaling pathways. Conclusion. Our result provides a new insight into cancer related mRNA coexpression network in CRC research.

Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging.

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Campbell, Jos L; SoRelle, Elliott D; Ilovich, Ohad; Liba, Orly; James, Michelle L; Qiu, Zhen; Perez, Valerie; Chan, Carmel T; de la Zerda, Adam; Zavaleta, Cristina

2017-08-01

Despite extensive research and development, new nano-based diagnostic contrast agents have faced major barriers in gaining regulatory approval due to their potential systemic toxicity and prolonged retention in vital organs. Here we use five independent biodistribution techniques to demonstrate that oral ingestion of one such agent, gold-silica Raman nanoparticles, results in complete clearance with no systemic toxicity in living mice. The oral delivery mimics topical administration to the oral cavity and gastrointestinal (GI) tract as an alternative to intravenous injection. Biodistribution and clearance profiles of orally (OR) vs. intravenously (IV) administered Raman nanoparticles were assayed over the course of 48 h. Mice given either an IV or oral dose of Raman nanoparticles radiolabeled with approximately 100 μCi (3.7MBq) of 64 Cu were imaged with dynamic microPET immediately post nanoparticle administration. Static microPET images were also acquired at 2 h, 5 h, 24 h and 48 h. Mice were sacrificed post imaging and various analyses were performed on the excised organs to determine nanoparticle localization. The results from microPET imaging, gamma counting, Raman imaging, ICP-MS, and hyperspectral imaging of tissue sections all correlated to reveal no evidence of systemic distribution of Raman nanoparticles after oral administration and complete clearance from the GI tract within 24 h. Paired with the unique signals and multiplexing potential of Raman nanoparticles, this approach holds great promise for realizing targeted imaging of tumors and dysplastic tissues within the oral cavity and GI-tract. Moreover, these results suggest a viable path for the first translation of high-sensitivity Raman contrast imaging into clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rare sugar D-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus.

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Hossain, Akram; Yamaguchi, Fuminori; Matsuo, Tatsuhiro; Tsukamoto, Ikuko; Toyoda, Yukiyasu; Ogawa, Masahiro; Nagata, Yasuo; Tokuda, Masaaki

2015-11-01

Obesity and type 2 diabetes mellitus (T2DM) are the leading worldwide risk factors for mortality. The inextricably interlinked pathological progression from excessive weight gain, obesity, and hyperglycemia to T2DM, usually commencing from obesity, typically originates from overconsumption of sugar and high-fat diets. Although most patients require medications, T2DM is manageable or even preventable with consumption of low-calorie diet and maintaining body weight. Medicines like insulin, metformin, and thiazolidinediones that improve glycemic control; however, these are associated with weight gain, high blood pressure, and dyslipidemia. These situations warrant the attentive consideration of the role of balanced foods. Recently, we have discovered advantages of a rare sugar, D-allulose, a zero-calorie functional sweetener having strong anti-hyperlipidemic and anti-hyperglycemic effects. Study revealed that after oral administration in rats D-allulose readily entered the blood stream and was eliminated into urine within 24h. Cell culture study showed that D-allulose enters into and leaves the intestinal enterocytes via glucose transporters GLUT5 and GLUT2, respectively. In addition to D-allulose's short-term effects, the characterization of long-term effects has been focused on preventing commencement and progression of T2DM in diabetic rats. Human trials showed that D-allulose attenuates postprandial glucose levels in healthy subjects and in borderline diabetic subjects. The anti-hyperlipidemic effect of D-allulose, combined with its anti-inflammatory actions on adipocytes, is beneficial for the prevention of both obesity and atherosclerosis and is accompanied by improvements in insulin resistance and impaired glucose tolerance. Therefore, this review presents brief discussions focusing on physiological functions and potential benefits of D-allulose on obesity and T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

Not all players are equally motivated: The role of narcissism.

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Roberts, Ross; Woodman, Tim; Lofthouse, Sian; Williams, Lucy

2015-01-01

Research on motivational climates consistently demonstrates that mastery-focused climates are associated with positive outcomes and ego-involving performance climates lead to maladaptive outcomes. However, the role of personality within such a framework has been largely ignored. To redress this imbalance, we examined the potential role of narcissism in moderating the effects of different motivational climates on leader-inspired extra effort in training. Training is where rugby players spend most of their rugby time and we were keen to examine the combination of personality and climate that might maximise the yield of such training environments. Female rugby players (n = 126) from 15 clubs completed measures of narcissism, motivational climate and effort. Moderated regression analyses revealed that narcissism moderated the relationship between motivational climate and effort. Increases in either performance or mastery climates were associated with increases in effort for narcissists; no such relationship was revealed for low narcissists. The findings demonstrate the importance of considering personality within rugby training environments, as it is clear that not every player will respond the same way to specific training conditions. Coaches who understand this and are able to tailor individualised motivational climates will likely gain the greatest benefits from their different players.

The Arabidopsis nox Mutant Lacking Carotene Hydroxylase Activity Reveals a Critical Role for Xanthophylls in Photosystem I Biogenesis[C][W

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Dall’Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

2013-01-01

Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth. PMID:23396829

Role of structural relaxations and chemical substitutions on piezoelectric fields and potential lineup in GaN/Al junctions

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Picozzi, S.; Profeta, G.; Continenza, A.; Massidda, S.; Freeman, A. J.

2002-04-01

First-principles full-potential linearized augmented plane wave calculations are performed to clarify the role of the interface geometry on piezoelectric fields and potential lineups in [0001] wurtzite and [111]-zincblende GaN/Al junctions. The electric field (polarity and magnitude) is found to be strongly affected by atomic relaxations in the interface region. A procedure is used to evaluate the Schottky-barrier height in the presence of electric fields, showing that their effect is relatively small (a few tenths of an eV). These calculations assess the rectifying behavior of the GaN/Al contact, in agreement with experimental values for the barrier. We disentangle chemical and structural effects on the relevant properties (such as the potential discontinuity and the electric field) by studying unrelaxed ideal nitride/metal systems. Using simple electronegativity arguments, we outline the leading mechanisms that define the values of the electric field and Schottky barrier in these ideal systems. Finally, the transitivity rule is proved to be well satisfied.

Exploring the Impact of Role-Playing on Peer Feedback in an Online Case-Based Learning Activity

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Yu-Hui Ching

2014-07-01

Full Text Available This study explored the impact of role-playing on the quality of peer feedback and learners’ perception of this strategy in a case-based learning activity with VoiceThread in an online course. The findings revealed potential positive impact of role-playing on learners’ generation of constructive feedback as role-playing was associated with higher frequency of problem identification in the peer comments. Sixty percent of learners perceived the role-play strategy useful in assisting them to compose and provide meaningful feedback. Multiple motivations drove learners in making decisions on role choice when responding to their peers, mostly for peer benefits. Finally, 90% of learners reported the peer feedback useful or somewhat useful. Based on the findings of this study, we discussed educational and instructional design implications and future directions to further the line of research using role-play strategy to enhance peer feedback activity.

The Role of Chaperone-subunit Usher Domain Interactions in the Mechanism of Bacterial Pilus Biogenesis Revealed by ESI-MS*

Science.gov (United States)

Morrissey, Bethny; Leney, Aneika C.; Toste Rêgo, Ana; Phan, Gilles; Allen, William J.; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E.; Radford, Sheena E.

2012-01-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species. PMID:22371487

The role of chaperone-subunit usher domain interactions in the mechanism of bacterial pilus biogenesis revealed by ESI-MS.

Science.gov (United States)

Morrissey, Bethny; Leney, Aneika C; Toste Rêgo, Ana; Phan, Gilles; Allen, William J; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E; Radford, Sheena E

2012-07-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species.

Chlorosis caused by two recessively interacting genes reveals a role of RNA helicase in hybrid breakdown in Arabidopsis thaliana.

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Plötner, Björn; Nurmi, Markus; Fischer, Axel; Watanabe, Mutsumi; Schneeberger, Korbinian; Holm, Svante; Vaid, Neha; Schöttler, Mark Aurel; Walther, Dirk; Hoefgen, Rainer; Weigel, Detlef; Laitinen, Roosa A E

2017-07-01

Hybrids often differ in fitness from their parents. They may be superior, translating into hybrid vigour or heterosis, but they may also be markedly inferior, because of hybrid weakness or incompatibility. The underlying genetic causes for the latter can often be traced back to genes that evolve rapidly because of sexual or host-pathogen conflicts. Hybrid weakness may manifest itself only in later generations, in a phenomenon called hybrid breakdown. We have characterized a case of hybrid breakdown among two Arabidopsis thaliana accessions, Shahdara (Sha, Tajikistan) and Lövvik-5 (Lov-5, Northern Sweden). In addition to chlorosis, a fraction of the F 2 plants have defects in leaf and embryo development, and reduced photosynthetic efficiency. Hybrid chlorosis is due to two major-effect loci, of which one, originating from Lov-5, appears to encode an RNA helicase (AtRH18). To examine the role of the chlorosis allele in the Lövvik area, in addition to eight accessions collected in 2009, we collected another 240 accessions from 15 collections sites, including Lövvik, from Northern Sweden in 2015. Genotyping revealed that Lövvik collection site is separated from the rest. Crosses between 109 accessions from this area and Sha revealed 85 cases of hybrid chlorosis, indicating that the chlorosis-causing allele is common in this area. These results suggest that hybrid breakdown alleles not only occur at rapidly evolving loci, but also at genes that code for conserved processes. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Potential role of some nutraceuticals in the regression of Alzheimer’s disease in an experimental animal model

OpenAIRE

AHMED, Hanna Hamdy; SHOUSHA, Wafaa Ghoneim; HUSSIEN, Rehab Mahmoud; FARRAG, Abdel Razik Hussein

2011-01-01

The goal of this study was to evaluate the potential role of some nutraceuticals, coenzyme Q10, vitamin B complex, and lecithin against aluminum-induced neurodegeneration characteristic of Alzheimer's disease. Materials and methods: Ninety-six male and female Sprague Dawley rats were divided into 2 main groups, namely female and male. Each group was divided into 6 subgroups. Group 1 served as control group. Group 2 was administered AlCl3 for 4 months. Groups 3, 4, 5, and 6 were adm...

Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials.

Science.gov (United States)

Cox, Anthony; Kohls, Gregor; Naples, Adam J; Mukerji, Cora E; Coffman, Marika C; Rutherford, Helena J V; Mayes, Linda C; McPartland, James C

2015-10-01

Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Graduate radiographers' expectations for role development - The potential impact of misalignment of expectation and valence on staff retention and service provision

Energy Technology Data Exchange (ETDEWEB)

Williamson, Keren [Department of Radiography, School of Healthcare Studies, Cardiff University, Heath Park, Cardiff CF14 4XN (United Kingdom)], E-mail: williamsonk2@cardiff.ac.uk; Mundy, Lynn A. [Department of Radiography, School of Healthcare Studies, Cardiff University, Heath Park, Cardiff CF14 4XN (United Kingdom)

2010-02-15

Purpose: The purpose of this study was to investigate the role development expectations of graduate radiographers with a view to predicting the potential impact of a misalignment of these expectations and valence on service delivery and staff retention. A final year cohort of radiography students completed a questionnaire designed to explore topics associated with role development opportunities. Method: Structured questionnaires, in the Likert scale format, utilised 20 attitude questions constructed to elicit information in relation to 3 main themes of investigation; expectation, valence and knowledge. Results: All participants (n = 37) stated an expectation for role development opportunities with 97.3% (n = 36) indicating that these expectations would be realised within 5 years of graduation and 75.7% (n = 28) within 2 years of graduation. A significant correlation between expectation for role development and job satisfaction was seen (p < 0.05). 81.1% (n = 30) of participants stated turnover intentions in order to meet their expectations. Conclusion: There is an expectation for role development opportunities for new graduates with a valence noted of the intrinsic reward of meeting these expectations. Expectation and valence are seen to be intrinsically linked with job satisfaction suggesting that misalignment of these would have a potentially negative impact on motivation and retention of the future radiography workforce demonstrating a positive correlation with withdrawal behaviours, including turnover intentions. In a relatively small professional group such as radiography the phenomenon of group cohesion may be strong suggesting that withdrawal behaviours may manifest as 'resignation in post', impacting on the quality of care and service provision for patients.

Energy Efficiency Potential in Existing Commercial Buildings: Review of Selected Recent Studies

Energy Technology Data Exchange (ETDEWEB)

Belzer, David B.

2009-04-03

This report reviews six recent studies (from 2002 through 2006) by states and utilities to assess the energy saving potential in existing commercial buildings. The studies cover all or portions of California, Connecticut, Vermont, Colorado, Illinois, and the Pacific Northwest. The studies clearly reveal that lighting remains the single largest and most cost effective end use that can be reduced to save energy. Overall the study indicated that with existing technologies and costs, a reasonable range of economic savings potential in existing commercial buildings is between 10 and 20 percent of current energy use. While not a focus of the study, an additional conclusion is that implementation of commercial building monitoring and controls would also play an important role in the nation’s efforts to improve energy efficiency of existing buildings.

Mexican-American adolescents' gender role attitude development: the role of adolescents' gender and nativity and parents' gender role attitudes.

Science.gov (United States)

Updegraff, Kimberly A; McHale, Susan M; Zeiders, Katharine H; Umaña-Taylor, Adriana J; Perez-Brena, Norma J; Wheeler, Lorey A; Rodríguez De Jesús, Sue A

2014-12-01

Gender development has long term implications for education and career endeavors and family formation behaviors, but we know very little about the role of sociocultural factors in developmental and individual differences. In this study, we investigated one domain of gender development, gender role attitudes, in Mexican-American adolescents (N = 246; 51 % female), using four phases of longitudinal data across 8 years. Data were collected when adolescents averaged 12.51 years (SD = 0.58), 14.64 years (SD = 0.59), 17.72 years (SD = 0.57), and 19.60 years of age (SD = 0.66). Mothers' and fathers' gender role attitudes also were assessed in Phases 1, 3, and 4. Findings revealed that gender attitude development varied as a function of the interaction between adolescents' nativity and gender. Among Mexico-born adolescents, females exhibited significant declines in traditional attitudes from early to late adolescence, but males' attitudes were stable over time. U.S.-born females and males, in contrast, did not differ in their gender attitude trajectories. Examining the links between mothers', fathers', and adolescents' gender role attitudes revealed within-person associations between mothers' and adolescents' gender role attitudes: on occasions when mothers reported more traditional attitudes relative to their own cross-time average, adolescents also reported more traditional attitudes than usual. In addition, fathers' more traditional gender role attitudes were associated with daughters', but not sons', more traditional gender role attitudes at the between-person level. The discussion focuses on the interpretation of Mexican-American adolescents' gender role attitude development from a cultural ecological perspective.

The development of control processes supporting source memory discrimination as revealed by event-related potentials.

Science.gov (United States)

de Chastelaine, Marianne; Friedman, David; Cycowicz, Yael M

2007-08-01

Improvement in source memory performance throughout childhood is thought to be mediated by the development of executive control. As postretrieval control processes may be better time-locked to the recognition response rather than the retrieval cue, the development of processes underlying source memory was investigated with both stimulus- and response-locked event-related potentials (ERPs). These were recorded in children, adolescents, and adults during a recognition memory exclusion task. Green- and red-outlined pictures were studied, but were tested in black outline. The test requirement was to endorse old items shown in one study color ("targets") and to reject new items along with old items shown in the alternative study color ("nontargets"). Source memory improved with age. All age groups retrieved target and nontarget memories as reflected by reliable parietal episodic memory (EM) effects, a stimulus-locked ERP correlate of recollection. Response-locked ERPs to targets and nontargets diverged in all groups prior to the response, although this occurred at an increasingly earlier time point with age. We suggest these findings reflect the implementation of attentional control mechanisms to enhance target memories and facilitate response selection with the greatest and least success, respectively, in adults and children. In adults only, response-locked ERPs revealed an early-onsetting parietal negativity for nontargets, but not for targets. This was suggested to reflect adults' ability to consistently inhibit prepotent target responses for nontargets. The findings support the notion that the development of source memory relies on the maturation of control processes that serve to enhance accurate selection of task-relevant memories.

The Role of the Gut Microbiota in Childhood Obesity.

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Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2016-08-01

Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

Science.gov (United States)

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A potential pathophysiological role for galectins and the renin-angiotensin system in preeclampsia.

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Blois, Sandra M; Dechend, Ralf; Barrientos, Gabriela; Staff, Anne Cathrine

2015-01-01

This review discusses a potential role of galectins and the renin-angiotensin system (RAS) in the pathophysiology of preeclampsia (PE). Preeclampsia affects between 3 and 5 % of all pregnancies and is a heterogeneous disease, which may be caused by multiple factors. The only cure is the delivery of the placenta, which may result in a premature delivery and baby. Probably due to its heterogeneity, PE studies in human have hitherto only led to the identification of a limited number of factors involved in the pathogenesis of the disease. Animal models, particularly in mice and rats, have been used to gain further insight into the molecular pathology behind PE. In this review, we discuss the picture emerging from human and animal studies pointing to galectins and the RAS being associated with the PE syndrome and affecting a broad range of cellular signaling components. Moreover, we review the epidemiological evidence for PE increasing the risk of future cardiovascular disease later in life.

Potential role of anticonvulsants in the treatment of obsessive-compulsive and related disorders.

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Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

2014-10-01

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Medication calculation: the potential role of digital game-based learning in nurse education.

Science.gov (United States)

Foss, Brynjar; Mordt Ba, Petter; Oftedal, Bjørg F; Løkken, Atle

2013-12-01

Medication dose calculation is one of several medication-related activities that are conducted by nurses daily. However, medication calculation skills appear to be an area of global concern, possibly because of low numeracy skills, test anxiety, low self-confidence, and low self-efficacy among student nurses. Various didactic strategies have been developed for student nurses who still lack basic mathematical competence. However, we suggest that the critical nature of these skills demands the investigation of alternative and/or supplementary didactic approaches to improve medication calculation skills and to reduce failure rates. Digital game-based learning is a possible solution because of the following reasons. First, mathematical drills may improve medication calculation skills. Second, games are known to be useful during nursing education. Finally, mathematical drill games appear to improve the attitudes of students toward mathematics. The aim of this article was to discuss common challenges of medication calculation skills in nurse education, and we highlight the potential role of digital game-based learning in this area.

Electric Mars: A large trans-terminator electric potential drop on closed magnetic field lines above Utopia Planitia

Science.gov (United States)

Collinson, Glyn; Mitchell, David; Xu, Shaosui; Glocer, Alex; Grebowsky, Joseph; Hara, Takuya; Lillis, Robert; Espley, Jared; Mazelle, Christian; Sauvaud, Jean-André; Fedorov, Andrey; Liemohn, Mike; Andersson, Laila; Jakosky, Bruce

2017-02-01

Parallel electric fields and their associated electric potential structures play a crucial role in ionospheric-magnetospheric interactions at any planet. Although there is abundant evidence that parallel electric fields play key roles in Martian ionospheric outflow and auroral electron acceleration, the fields themselves are challenging to directly measure due to their relatively weak nature. Using measurements by the Solar Wind Electron Analyzer instrument aboard the NASA Mars Atmosphere and Volatile EvolutioN (MAVEN) Mars Scout, we present the discovery and measurement of a substantial (ΦMars=7.7 ± 0.6 V) parallel electric potential drop on closed magnetic field lines spanning the terminator from day to night above the great impact basin of Utopia Planitia, a region largely free of crustal magnetic fields. A survey of the previous 26 orbits passing over a range of longitudes revealed similar signatures on seven orbits, with a mean potential drop (ΦMars) of 10.9 ± 0.8 V, suggestive that although trans-terminator electric fields of comparable strength are not ubiquitous, they may be common, at least at these northerly latitudes.

Electric Mars: A Large Trans-Terminator Electric Potential Drop on Closed Magnetic Field Lines Above Utopia Planitia

Science.gov (United States)

Collinson, Glyn; Mitchell, David; Xu, Shaosui; Glocer, Alex; Grebowsky, Joseph; Hara, Takuya; Lillis, Robert; Espley, Jared; Mazelle, Christian; Sauvaud, Jean-Andre

2017-01-01

Abstract Parallel electric fields and their associated electric potential structures play a crucial role inionospheric-magnetospheric interactions at any planet. Although there is abundant evidence that parallel electric fields play key roles in Martian ionospheric outflow and auroral electron acceleration, the fields themselves are challenging to directly measure due to their relatively weak nature. Using measurements by the Solar Wind Electron Analyzer instrument aboard the NASA Mars Atmosphere and Volatile EvolutioN(MAVEN) Mars Scout, we present the discovery and measurement of a substantial (Phi) Mars 7.7 +/-0.6 V) parallel electric potential drop on closed magnetic field lines spanning the terminator from day to night above the great impact basin of Utopia Planitia, a region largely free of crustal magnetic fields. A survey of the previous 26 orbits passing over a range of longitudes revealed similar signatures on seven orbits, with a mean potential drop (Phi) Mars of 10.9 +/- 0.8 V, suggestive that although trans-terminator electric fields of comparable strength are not ubiquitous, they may be common, at least at these northerly latitudes.

A potential role for tetranectin in mineralization during osteogenesis

DEFF Research Database (Denmark)

Wewer, U M; Ibaraki, K; Schjørring, P

1994-01-01

approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p role during...... to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis...... and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained...

Perfusion magnetic resonance imaging characteristics of intracerebral tuberculomas and its role in differentiating tuberculomas from metastases

Energy Technology Data Exchange (ETDEWEB)

Sankhe, Shilpa; Baheti, Akshay [Dept. of Radiology, Seth GS Medical Coll. and KEM Hospital, Thane (India)], e-mail: akshaybaheti@gmail.com; Ihare, Ashish; Mathur, Shobhit; Dabhade, Poonam; Sarode, Ashish [Dept. of Radiology, Seth GS Medical Coll. and KEM Hospital, Thane (India)

2013-04-15

Background: Intracerebral tuberculomas usually manifest as ring-enhancing of nodular lesions on magnetic resonance imaging (MRI). These imaging findings are also observed in other lesions like metastases and toxoplasmosis. Purpose: To study the MRI perfusion characteristics of tuberculomas and its potential role in their definitive diagnosis. Material and Methods: Thirty-four tuberculomas were evaluated by conventional and perfusion MRI. The relative cerebral blood volume (rCBV) values of the center, peripheral wall, and perilesional neuroparenchymal tissue were calculated using rCBV maps. Ten ring-enhancing metastases were similarly evaluated and rCBV values of their peripheral walls were calculated. Results: Thirty-one of the 34 tuberculomas were ring-enhancing or conglomerate lesions and revealed hypoperfused centers with hyperperfused peripheral walls, with the mean rCBV {+-} SD being 0.42 {+-} 0.25 and 2.04 {+-} 0.61, respectively. Three nodular enhancing lesions showed predominantly homogenous hyperperfusion, with the mean rCBV measuring 2.96 {+-} 0.39 (mean {+-} SD). The perilesional neuroparenchyma was hypoperfused in both cases. The metastases revealed mean rCBV ratio of the peripheral wall to be 5.43 {+-} 2.1 (mean {+-} SD). Analysis of the values by ROC curve method revealed a cut-off value of {>=}3.745 for differentiating ring-enhancing metastases from ring-enhancing tuberculomas. Conclusion: Perfusion MR is a useful tool for the assessment of tuberculomas and can help differentiate them from neoplasms like metastases. It also has a potential role in monitoring therapy and for early detection of drug resistance.

The role of the ion-molecule and molecule-molecule interactions in the formation of the two-ion average force interaction potential

CERN Document Server

Ajrian, E A; Sidorenko, S N

2002-01-01

The effect of the ion-molecule and intermolecular interactions on the formation of inter-ion average force potentials is investigated within the framework of a classical ion-dipole model of electrolyte solutions. These potentials are shown to possess the Coulomb asymptotics at large distances while in the region of mean distances they reveal creation and disintegration of solvent-shared ion pairs. The calculation results provide a qualitatively authentic physical picture which is experimentally observed in strong electrolytes solutions. In particular, an increased interaction between an ion and a molecule enhances formation of ion pairs in which the ions are separated by one solvent molecule

X-ray fluorescence microscopy reveals the role of selenium in spermatogenesis

OpenAIRE

Kehr, Sebastian; Malinouski, Mikalai; Finney, Lydia; Vogt, Stefan; Labunskyy, Vyacheslav M.; Kasaikina, Marina V.; Carlson, Bradley A.; Zhou, You; Hatfield, Dolph L.; Gladyshev, Vadim N.

2009-01-01

Selenium (Se) is a trace element with important roles in human health. Several selenoproteins have essential functions in development. However, the cellular and tissue distribution of Se remains largely unknown because of the lack of analytical techniques that image this element with sufficient sensitivity and resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be used to visualize and quantify the tissue, cellular and subcellular topography of Se. We applied this techn...

Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

Science.gov (United States)

Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

2013-01-01

Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

Quantitative membrane proteomics reveals a role for tetraspanin enriched microdomains during entry of human cytomegalovirus.

Directory of Open Access Journals (Sweden)

Kasinath Viswanathan

Full Text Available Human cytomegalovirus (HCMV depends on and modulates multiple host cell membrane proteins during each stage of the viral life cycle. To gain a global view of the impact of HCMV-infection on membrane proteins, we analyzed HCMV-induced changes in the abundance of membrane proteins in fibroblasts using stable isotope labeling with amino acids (SILAC, membrane fractionation and protein identification by two-dimensional liquid chromatography and tandem mass spectrometry. This systematic approach revealed that CD81, CD44, CD98, caveolin-1 and catenin delta-1 were down-regulated during infection whereas GRP-78 was up-regulated. Since CD81 downregulation was also observed during infection with UV-inactivated virus we hypothesized that this tetraspanin is part of the viral entry process. Interestingly, additional members of the tetraspanin family, CD9 and CD151, were also downregulated during HCMV-entry. Since tetraspanin-enriched microdomains (TEM cluster host cell membrane proteins including known CMV receptors such as integrins, we studied whether TEMs are required for viral entry. When TEMs were disrupted with the cholesterol chelator methyl-β-cylcodextrin, viral entry was inhibited and this inhibition correlated with reduced surface levels of CD81, CD9 and CD151, whereas integrin levels remained unchanged. Furthermore, simultaneous siRNA-mediated knockdown of multiple tetraspanins inhibited viral entry whereas individual knockdown had little effect suggesting essential, but redundant roles for individual tetraspanins during entry. Taken together, our data suggest that TEM act as platforms for receptors utilized by HCMV for entry into cells.

Comparative single-cell genomics reveals potential ecological niches for the freshwater acI Actinobacteria lineage.

Science.gov (United States)

Ghylin, Trevor W; Garcia, Sarahi L; Moya, Francisco; Oyserman, Ben O; Schwientek, Patrick; Forest, Katrina T; Mutschler, James; Dwulit-Smith, Jeffrey; Chan, Leong-Keat; Martinez-Garcia, Manuel; Sczyrba, Alexander; Stepanauskas, Ramunas; Grossart, Hans-Peter; Woyke, Tanja; Warnecke, Falk; Malmstrom, Rex; Bertilsson, Stefan; McMahon, Katherine D

2014-12-01

Members of the acI lineage of Actinobacteria are the most abundant microorganisms in most freshwater lakes; however, our understanding of the keys to their success and their role in carbon and nutrient cycling in freshwater systems has been hampered by the lack of pure cultures and genomes. We obtained draft genome assemblies from 11 single cells representing three acI tribes (acI-A1, acI-A7, acI-B1) from four temperate lakes in the United States and Europe. Comparative analysis of acI SAGs and other available freshwater bacterial genomes showed that acI has more gene content directed toward carbohydrate acquisition as compared to Polynucleobacter and LD12 Alphaproteobacteria, which seem to specialize more on carboxylic acids. The acI genomes contain actinorhodopsin as well as some genes involved in anaplerotic carbon fixation indicating the capacity to supplement their known heterotrophic lifestyle. Genome-level differences between the acI-A and acI-B clades suggest specialization at the clade level for carbon substrate acquisition. Overall, the acI genomes appear to be highly streamlined versions of Actinobacteria that include some genes allowing it to take advantage of sunlight and N-rich organic compounds such as polyamines, di- and oligopeptides, branched-chain amino acids and cyanophycin. This work significantly expands the known metabolic potential of the cosmopolitan freshwater acI lineage and its ecological and genetic traits.

Phenotype anchoring in zebrafish reveals a potential role for matrix metalloproteinases (MMPs) in tamoxifen's effects on skin epithelium

Energy Technology Data Exchange (ETDEWEB)

Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu; Wehmas, Leah C., E-mail: wehmasl@onid.oregonstate.edu; La Du, Jane K., E-mail: Jane.LaDu@oregonstate.edu; Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu

2016-04-01

The zebrafish is a powerful alternative model used to link phenotypes with molecular effects to discover drug mode of action. Using a zebrafish embryo-larval toxicity bioassay, we evaluated the effects of tamoxifen — a widely used anti-estrogen chemotherapeutic. Zebrafish exposed to ≥ 10 μM tamoxifen exhibited a unique necrotic caudal fin phenotype that was rapidly induced regardless of developmental life-stage when treatment was applied. To define tamoxifen's bioactivity resulting in this phenotype, targeted gene expression was used to evaluate 100 transcripts involved in tissue remodeling, calcium signaling, cell cycle and cell death, growth factors, angiogenesis and hypoxia. The most robustly misregulated transcripts in the tail were matrix metalloproteinases mmp9 and mmp13a, induced 127 and 1145 fold, respectively. Expression of c-fos, c-jun, and ap1s1 were also moderately elevated (3–7 fold), consistent with AP-1 activity — a transcription factor that regulates MMP expression. Immunohistochemistry confirmed high levels of induction for MMP13a in affected caudal fin skin epithelial tissue. The necrotic caudal fin phenotype was significantly attenuated or prevented by three functionally unique MMP inhibitors: EDTA (metal chelator), GM 6001 (broad MMP inhibitor), and SR 11302 (AP-1 transcription factor inhibitor), suggesting MMP-dependence. SR 11302 also inhibited induction of mmp9, mmp13a, and a putative MMP target, igfbp1a. Overall, our studies suggest that tamoxifen's effect is the result of perturbation of the MMP system in the skin leading to ectopic expression, cytotoxicity, and the necrotic caudal fin phenotype. These studies help advance our understanding of tamoxifen's non-classical mode of action and implicate a possible role for MMPs in tissues such as skin. - Highlights: • Tamoxifen rapidly induced a unique necrotic caudal fin phenotype in zebrafish. • Apoptosis co-localized temporally and spatially in the necrotic tail. �

The roles of teachers' science talk in revealing language demands within diverse elementary school classrooms: a study of teaching heat and temperature in Singapore

Science.gov (United States)

Seah, Lay Hoon; Yore, Larry D.

2017-01-01

This study of three science teachers' lessons on heat and temperature seeks to characterise classroom talk that highlighted the ways language is used and to examine the nature of the language demands revealed in constructing, negotiating, arguing and communicating science ideas. The transcripts from the entire instructional units for these teachers' four culturally and linguistically diverse Grade 4 classes (10 years old) with English as the language of instruction constitute the data for this investigation. Analysis of these transcripts focused on teachers' talk that made explicit reference to the form or function of the language of science and led to the inductive development of the 'Attending to Language Demands in Science' analytical framework. This framework in turn revealed that the major foregrounding purposes of teachers' talk include labelling, explaining, differentiating, selecting and constructing. Further classification of the instances within these categories revealed the extensive and contextualised nature of the language demands. The results challenge the conventional assumption that basic literacy skills dominate over disciplinary literacy skills in primary school science. Potential uses of the analytical framework that could further expand our understanding of the forms, functions and demands of language used in elementary school science are also discussed.

The role of identification in dynamic psychiatry and psychotherapy.

Science.gov (United States)

Corradi, Richard B

2011-01-01

Identification-a psychic process in which a person takes on characteristics of another-is a concept important to the understanding of human nature. It plays an important role in how our personalities develop, in our ability to deal with life's stresses, and in how we interact with other people. Knowledge of its manifestations is essential to dynamic psychiatry and to its applications in psychotherapy. This article defines identification and reviews its role in development and as a defense. It discusses its role in the psychopathology of disorders commonly encountered in psychotherapy practice-depression and anxiety states reactive to losses in life, and borderline states. Clinical vignettes illustrate how identification functions in these conditions, and also how identifications reveal themselves in the transference and are utilized in psychotherapy. A teaching vignette illustrates how important it is that residents learning the art of psychotherapy appreciate the therapeutic potential of identification. The article maintains that, although it often goes unrecognized, identification with the therapist is one of the most effective therapeutic devices in the transference.

Small RNA profiling reveals important roles for miRNAs in Arabidopsis response to Bacillus velezensis FZB42.

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Xie, Shanshan; Jiang, Haiyang; Xu, Zhilan; Xu, Qianqian; Cheng, Beijiu

2017-09-20

Bacillus velezensis FZB42 (previously classified as Bacillus amyloliquefaciens FZB42) has been confirmed to successfully colonize plant roots and enhance defense response against pathogen infection. This study indicated that FZB42 inoculation enhanced Arabidopsis defense response against Pseudomonas syringae DC3000 through inducing the expression of PR1, PDF1.2 and stomata closure. To further clarify the induced defense response at miRNA level, sRNA libraries from Arabidopsis roots inoculated with FZB42 and control were constructed and sequenced. The reads of 21nt and 24nt in length were the most abundant groups in FZB42-treated library and control library, respectively. 234 known miRNAs and 16 novel miRNAs were identified. Among them, 11 known miRNAs and 4 novel miRNAs were differentially expressed after FZB42 inoculation. Moreover cis-elements (TC-rich repeats, TCA-element and CGTCA-motif) associated with plant defense were also found in the promoters of these miRNAs. Additionally, 141 mRNAs were predicted as potential targets of these differentially expressed miRNAs. GO annotations of the target genes indicated their potential roles in polyamine biosynthetic process and intracellular protein transport biological process, which may contribute to increased defense response. Our findings indicated that Bacillus velezensis FZB42 inoculation altered the expression of Arabidopsis miRNAs and their target genes, which were associated with defense response. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

V. N. Livina

2010-02-01

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

Daclatasvir: potential role in hepatitis C

Directory of Open Access Journals (Sweden)

Lee C

2013-10-01

Full Text Available Choongho Lee College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea  Abstract: Chronic hepatitis C virus (HCV infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

Identification of a novel pro-inflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis

Science.gov (United States)

LAGGNER, Ute; DI MEGLIO, Paola; PERERA, Gayathri K.; HUNDHAUSEN, Christian; LACY, Katie E.; ALI, Niwa; SMITH, Catherine H.; HAYDAY, Adrian C.; NICKOLOFF, Brian J.; NESTLE, Frank O.

2011-01-01

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is poorly characterized. In this study we show in vivo evidence that human blood contains a distinct subset of pro-inflammatory cutaneous lymphocyte antigen (CLA) and C-C chemokine receptor (CCR) 6 positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of pro-inflammatory mediators including IL-17A and activated keratinocytes in a TNF-α and IFN-γ dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared to healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, this data indicates redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human pro-inflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. PMID:21813772

Potential ecological roles of artemisinin produced by Artemisia annua L.

Science.gov (United States)

Knudsmark Jessing, Karina; Duke, Stephen O; Cedergreeen, Nina

2014-02-01

Artemisia annua L. (annual wormwood, Asteraceae) and its secondary metabolite artemisinin, a unique sesquiterpene lactone with an endoperoxide bridge, has gained much attention due to its antimalarial properties. Artemisinin has a complex structure that requires a significant amount of energy for the plant to synthesize. So, what are the benefits to A. annua of producing this unique compound, and what is the ecological role of artemisinin? This review addresses these questions, discussing evidence of the potential utility of artemisinin in protecting the plant from insects and other herbivores, as well as pathogens and competing plant species. Abiotic factors affecting the artemisinin production, as well as mechanisms of artemisinin release to the surroundings also are discussed, and new data are provided on the toxicity of artemisinin towards soil and aquatic organisms. The antifungal and antibacterial effects reported are not very pronounced. Several studies have reported that extracts of A. annua have insecticidal effects, though few studies have proven that artemisinin could be the single compound responsible for the observed effects. However, the pathogen(s) or insect(s) that may have provided the selection pressure for the evolution of artemisinin synthesis may not have been represented in the research thus far conducted. The relatively high level of phytotoxicity of artemisinin in soil indicates that plant/plant allelopathy could be a beneficial function of artemisinin to the producing plant. The release routes of artemisinin (movement from roots and wash off from leaf surfaces) from A. annua to the soil support the rationale for allelopathy.

Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

Science.gov (United States)

Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique

2018-03-01

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors. Copyright © 2018 Elsevier Inc. All rights reserved.

Metagenomic analysis of microbial consortia enriched from compost: new insights into the role of Actinobacteria in lignocellulose decomposition.

Science.gov (United States)

Wang, Cheng; Dong, Da; Wang, Haoshu; Müller, Karin; Qin, Yong; Wang, Hailong; Wu, Weixiang

2016-01-01

Compost habitats sustain a vast ensemble of microbes specializing in the degradation of lignocellulosic plant materials and are thus important both for their roles in the global carbon cycle and as potential sources of biochemical catalysts for advanced biofuels production. Studies have revealed substantial diversity in compost microbiomes, yet how this diversity relates to functions and even to the genes encoding lignocellulolytic enzymes remains obscure. Here, we used a metagenomic analysis of the rice straw-adapted (RSA) microbial consortia enriched from compost ecosystems to decipher the systematic and functional contexts within such a distinctive microbiome. Analyses of the 16S pyrotag library and 5 Gbp of metagenomic sequence showed that the phylum Actinobacteria was the predominant group among the Bacteria in the RSA consortia, followed by Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidetes. The CAZymes profile revealed that CAZyme genes in the RSA consortia were also widely distributed within these bacterial phyla. Strikingly, about 46.1 % of CAZyme genes were from actinomycetal communities, which harbored a substantially expanded catalog of the cellobiohydrolase, β-glucosidase, acetyl xylan esterase, arabinofuranosidase, pectin lyase, and ligninase genes. Among these communities, a variety of previously unrecognized species was found, which reveals a greater ecological functional diversity of thermophilic Actinobacteria than previously assumed. These data underline the pivotal role of thermophilic Actinobacteria in lignocellulose biodegradation processes in the compost habitat. Besides revealing a new benchmark for microbial enzymatic deconstruction of lignocelluloses, the results suggest that actinomycetes found in compost ecosystems are potential candidates for mining efficient lignocellulosic enzymes in the biofuel industry.

The Potential Role of Arbuscular Mycorrhizal Fungi in the Restoration of Degraded Lands

Science.gov (United States)

Asmelash, Fisseha; Bekele, Tamrat; Birhane, Emiru

2016-01-01

Experiences worldwide reveal that degraded lands restoration projects achieve little success or fail. Hence, understanding the underlying causes and accordingly, devising appropriate restoration mechanisms is crucial. In doing so, the ever-increasing aspiration and global commitments in degraded lands restoration could be realized. Here we explain that arbuscular mycorrhizal fungi (AMF) biotechnology is a potential mechanism to significantly improve the restoration success of degraded lands. There are abundant scientific evidences to demonstrate that AMF significantly improve soil attributes, increase above and belowground biodiversity, significantly improve tree/shrub seedlings survival, growth and establishment on moisture and nutrient stressed soils. AMF have also been shown to drive plant succession and may prevent invasion by alien species. The very few conditions where infective AMF are low in abundance and diversity is when the soil erodes, is disturbed and is devoid of vegetation cover. These are all common features of degraded lands. Meanwhile, degraded lands harbor low levels of infective AMF abundance and diversity. Therefore, the successful restoration of infective AMF can potentially improve the restoration success of degraded lands. Better AMF inoculation effects result when inocula are composed of native fungi instead of exotics, early seral instead of late seral fungi, and are consortia instead of few or single species. Future research efforts should focus on AMF effect on plant community primary productivity and plant competition. Further investigation focusing on forest ecosystems, and carried out at the field condition is highly recommended. Devising cheap and ethically widely accepted inocula production methods and better ways of AMF in situ management for effective restoration of degraded lands will also remain to be important research areas. PMID:27507960

Transient receptor potential channels in essential hypertension

DEFF Research Database (Denmark)

Liu, Daoyan; Scholze, Alexandra; Zhu, Zhiming

2006-01-01

The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated.......The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated....

Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration

Directory of Open Access Journals (Sweden)

Bill Tachtsis

2018-03-01

Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs, which are commonly found in fish oil supplements, are known to possess anti-inflammatory properties and more recently alter skeletal muscle function. In this review, we discuss novel findings related to how n-3 PUFAs modulate molecular signaling responsible for growth and hypertrophy as well as the activity of muscle stem cells. Muscle stem cells commonly known as satellite cells, are primarily responsible for driving the skeletal muscle repair process to potentially damaging stimuli, such as mechanical stress elicited by exercise contraction. To date, there is a paucity of human investigations related to the effects of n-3 PUFAs on satellite cell content and activity. Based on current in vitro investigations, this review focuses on novel mechanisms linking n-3 PUFA’s to satellite cell activity and how they may improve muscle repair. Understanding the role of n-3 PUFAs during muscle growth and regeneration in association with exercise could lead to the development of novel supplementation strategies that increase muscle mass and strength, therefore possibly reducing the burden of muscle wasting with age.

Nuclear system for problems of environment, economy, and energy. (1) Nuclear energy role and potential for energy system in Asia

International Nuclear Information System (INIS)

Ujita, Hiroshi; Matsui, Kazuaki; Sekimoto, Hiroshi

2005-01-01

Role and potential of nuclear energy system in the energy options is discussed from the viewpoint of sustainable development with protecting from global warming. It is important for mitigation of global warming that the developing countries will use nuclear power effectively. The policy that nuclear power is considered as Clean Development Mechanism would be the good measure for that. (author)

Brainstem evoked potentials in infantile spasms

International Nuclear Information System (INIS)

Miyazaki, Masahito; Hashimoto, Toshiaki; Murakawa, Kazuyoshi; Tayama, Masanobu; Kuroda, Yasuhiro

1992-01-01

In ten patients with infantile spasms, brainstem evoked potentials and MRI examinations were performed to evaluate the brainstem involvement. The result of short latency somatosensory evoked potentials (SSEP) following the right median nerve stimulation revealed abnormal findings including the absence or low amplitudes of the waves below wave P3 and delayed central conduction time in 7 of the ten patients. The result of auditory brainstem responses (ABR) revealed abnormal findings including low amplitudes of wave V, prolonged interpeak latency of waves I-V and absence of the waves below wave IV in 5 of the ten patients. The result of the MRI examinations revealed various degrees of the brainstem atrophy in 6 of the ten patients, all of whom showed abnormal brainstem evoked potentials. The result of this study demonstrates that patients with infantile spasms are frequently associated with brainstem dysfunction and raises the possibility that brainstem atrophy might be a cause of infantile spasms. (author)

The role of Drosophila Piezo in mechanical nociception.

Science.gov (United States)

Kim, Sung Eun; Coste, Bertrand; Chadha, Abhishek; Cook, Boaz; Patapoutian, Ardem

2012-02-19

Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo

Nuclear Energy Center Site Survey, 1975. Part II. The U.S. electric power system and the potential role of nuclear energy centers

International Nuclear Information System (INIS)

1976-01-01

Information related to Nuclear Energy Centers (NEC) in the U.S. is presented concerning the U.S. electric power system today; electricity demand history and forecasts; history and forecasts of the electric utility industry; regional notes; the status, history, and forecasts of the nuclear role; power plant siting problems and practices; nuclear facilities siting problems and practices; origin and evolution of the nuclear energy center concept; conceptualized description of nuclear energy centers; potential role of nuclear energy centers; assumptions, criteria, and bases; typical evolution of a nuclear energy center; and the nuclear fuel cycle

Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

Science.gov (United States)

Okusaga, Olaoluwa O

2014-08-01

Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

Vitamin D: new roles and therapeutic potential in inflammatory bowel disease.

LENUS (Irish Health Repository)

Raftery, Tara

2012-11-01

Inflammatory bowel disease (IBD) encompasses 2 independent but related entities: ulcerative colitis (UC) and Crohn\\'s disease. Crohn\\'s disease is characterised by transmural patchy inflammation which can involve any portion of the gastrointestinal tract. UC is characterised by superficial inflammation that begins in the rectum and extends proximally along the colon. In Europe, approximately 2.2 million people have a diagnosis of IBD. The aetiology of IBD is unknown, however, immune, environmental and genetic factors are thought to be involved. Individuals with IBD are at risk of developing osteoporosis. In line with this, there are clear guidelines that recommend vitamin D supplementation for IBD patients to prevent bone disease, especially when undergoing steroid treatment. Despite an established role for vitamin D in IBD, deficiency is common. More novel effects of vitamin D beyond bone are emerging. It is now well established that vitamin D is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. The efficacy of vitamin D as an immune modulator in IBD remains to be proven. This review aims to evaluate the evidence implicating vitamin D deficiency in IBD pathogenesis, to examine vitamin D\\'s anti-inflammatory mechanisms and to explore its therapeutic potential, optimal serum levels and dietary intakes which may support immune function in this disease.

Potentially three distinct roles for hypoxic cell sensitizers in the clinic

International Nuclear Information System (INIS)

Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

1979-01-01

Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

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

Directory of Open Access Journals (Sweden)

Richard Allen White III

2015-09-01

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

Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases.

Science.gov (United States)

Roth, Andrew; Kyzar, Evan J; Cachat, Jonathan; Stewart, Adam Michael; Green, Jeremy; Gaikwad, Siddharth; O'Leary, Timothy P; Tabakoff, Boris; Brown, Richard E; Kalueff, Allan V

2013-01-10

Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming. Copyright © 2012 Elsevier Inc. All rights reserved.

Trade potential of climate smart goods of Vietnam: An application of gravity model

Directory of Open Access Journals (Sweden)

Trung Van Vu

2016-01-01

Full Text Available This paper examines the trade potential of climate smart goods (CSG of Vietnam. In particular, the study employs gravity model with panel data for bilateral trade between Vietnam and its 45 partners from 2002 to 2013 with an objective of identifying the determinants explaining Vietnam's trade of climate smart products. The estimation results reveal that economic size, market size, distance, real exchange rate, border, and the quality of infrastructure of both Vietnam and its trading partners play a major role in bilateral trade of CSG. Additionally, the paper applies the method using speed of convergence and the estimated gravity equation to answer whether Vietnam has fully realized the potential trade of CSG. Accordingly, Vietnam has strong opportunity for trade expansion with 19 out of 45 countries in the scope of this paper.

Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials.

Directory of Open Access Journals (Sweden)

Heike Althen

Full Text Available The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN, an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.

IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers.

Science.gov (United States)

Frantzi, Maria; Zoidakis, Jerome; Papadopoulos, Theofilos; Zürbig, Petra; Katafigiotis, Ioannis; Stravodimos, Konstantinos; Lazaris, Andreas; Giannopoulou, Ioanna; Ploumidis, Achilles; Mischak, Harald; Mullen, William; Vlahou, Antonia

2013-09-06