gebhart/patrepeval huggingface dataset:
Metabolic Syndrome Pandemic (2008)

The metabolic syndrome is a multiplex risk factor that consists of several risk correlates of metabolic origin. In addition, to dyslipidemia, hypertension, and hyperglycermia, the syndrome carries a prothrombotic state and a proinflammatory state. Persons with the metabolic syndrome are at essentially twice the risk for cardiovascular disease compared with those without the syndrome. It further raises the risk for type 2 diabetes by about 5-fold. Although some investigators favor keeping risk factors separate for purposes of clinical management, others believe that identifying individuals with an aggregation of risk factors provides additional useful information to guide clinical management. In particular it focuses attention on obesity and sedentary life habits that are the root of the syndrome. This review addresses the prevalence of this clustering phenomenon throughout the world. Such seems appropriate because of the increasing prevalence of obesity in almost all countries. The available evidence indicates that in most countries between 20% and 30% of the adult population can be characterized as having the metabolic syndrome. In some populations or segments of the population, the prevalence is even higher. On the other hand, in parts of developing world in which young adults predominate, the prevalence is lower; but with increasing affluence and aging of the population, the prevalence undoubtedly with rise.
Cover Picture: Eur. J. Immunol. 5/10 (2010)

Abstract This issue's cover image is provided by Chen et al ., the authors of “ A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses ” ( pp . 1451–1460). The image depicts immunofluorescent staining of mouse spleen frozen sections and demonstrates that FITC‐conjugated heat‐killed E. coli are efficiently captured by spleen marginal zone macrophages – a process that is facilitated by MARCO expressed on macrophages.
Cell Growth and Size Homeostasis in Proliferating Animal Cells (2009)

A long-standing question in biology is whether there is an intrinsic mechanism for coordinating growth and the cell cycle in metazoan cells. We examined cell size distributions in populations of lymphoblasts and applied a mathematical analysis to calculate how growth rates vary with both cell size and the cell cycle. Our results show that growth rate is size-dependent throughout the cell cycle. After initial growth suppression, there is a rapid increase in growth rate during the G1 phase, followed by a period of constant exponential growth. The probability of cell division varies independently with cell size and cell age. We conclude that proliferating mammalian cells have an intrinsic mechanism that maintains cell size.
A Crystalline Mesoporous Coordination Copolymer with High Microporosity (2007)

Mixing it up: UMCM-1 (University of Michigan Crystalline Material-1), a mesoporous material with unprecedented levels of microporosity, arises from the coordination copolymerization of a dicarboxylate and a tricarboxylate linker mediated by zinc (see picture; blue tetrahedra Zn4O clusters, C gray, H white, O red). Exceptionally high surface area derives from the microporous cages lining the 1D mesoporous channels. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705020_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effect of structural parameters of peptides on dimer formation and highly oxidized side products in the oxidation of thiols of linear analogues of human β‐defensin 3 by DMSO (2008)

The purpose of this study was to examine the effects of structural parameters of peptides on their oxidation by DMSO, including location of cysteine, effect of adjunct group participation, molecular hydrophobicity, steric hindrance or the accessibility of thiol group and peptide conformation, on oxidation rates, dimer formation and associated side products. We designed and synthesized two series of linear cysteine-containing analogues of human beta-defensin 3 (the C1-peptides with cysteine at the N-terminus residue 1, the C29-peptides with cysteine located at residue 29 in the centre of peptide), which were used for preparation of disulphide-linked homodimers. HPLC-ESI-MS was used to monitor the oxidation process and to characterize the molecular weights of dimers and side products of high oxidation. The formations of dimers and side products were dependent on the position of cysteines. Hydrophobicity generally rendered the thiol groups less accessible and hence exposed them to slow oxidation to form dimers (or even fail to form dimers during the timescale of observation). Molecular dynamics simulations showed that the exposure of cysteines (and sulphurs) of the C1-peptides was much larger than for the C29-peptides. The larger hydrophobic side chains tended to enable clustering of the side chains that sequester cysteine, particularly in the C29-peptides, which provided a molecular explanation for the observed trends in oxidation rates. Together with molecular modelling, we propose a reaction mechanism to elucidate the oxidation results of these peptides.
Activation of human factor X (Stuart factor) by a protease from Russell's viper venom (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActivation of human factor X (Stuart factor) by a protease from Russell's viper venomRichard G. Di Scipio, Mark A. Hermodson, and Earl W. DavieCite this: Biochemistry 1977, 16, 24, 5253–5260Publication Date (Print):November 1, 1977Publication History Published online1 May 2002Published inissue 1 November 1977https://pubs.acs.org/doi/10.1021/bi00643a015https://doi.org/10.1021/bi00643a015research-articleACS PublicationsRequest reuse permissionsArticle Views192Altmetric-Citations86LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Field-Assisted Splitting of Pure Water Based on Deep-Sub-Debye-Length Nanogap Electrochemical Cells (2017)

Owing to the low conductivity of pure water, using an electrolyte is common for achieving efficient water electrolysis. In this paper, we have fundamentally broken through this common sense by using deep-sub-Debye-length nanogap electrochemical cells to achieve efficient electrolysis of pure water (without any added electrolyte) at room temperature. A field-assisted effect resulted from overlapped electrical double layers can greatly enhance water molecules ionization and mass transport, leading to electron-transfer limited reactions. We have named this process "virtual breakdown mechanism" (which is completely different from traditional mechanisms) that couples the two half-reactions together, greatly reducing the energy losses arising from ion transport. This fundamental discovery has been theoretically discussed in this paper and experimentally demonstrated in a group of electrochemical cells with nanogaps between two electrodes down to 37 nm. On the basis of our nanogap electrochemical cells, the electrolysis current density from pure water can be significantly larger than that from 1 mol/L sodium hydroxide solution, indicating the much better performance of pure water splitting as a potential for on-demand clean hydrogen production.
pH and Ionic Strength Dependence of Protein (Un)Folding and Ligand Binding to Bovine β-Lactoglobulins A and B (2002)

Formation of complexes between bovine beta-lactoglobulins (BLG) and long-chain fatty acids (FAs), effect of complex formation on protein stability, and effects of pH and ionic strength on both complex formation and protein stability were investigated as a function of pH and ionic strength by electrophoretic techniques and NMR spectroscopy. The stability of BLG against unfolding is sharply affected by the pH of the medium: both A and B BLG variants are maximally stabilized against urea denaturation at acidic pH and against SDS denaturation at alkaline pH. The complexes of BLGB with oleic (OA) and palmitic acid (PA) appear more stable than the apoprotein at neutral pH whereas no differential behavior is observed in acidic and alkaline media. PA forms with BLG more stable complexes than OA. The difference between the denaturant concentration able to bring about protein unfolding in the holo versus the apo forms is larger for urea than for SDS treatment. This evidence disfavors the hypothesis of strong hydrophobic interactions being involved in complex formation. Conversely, a significant contribution to FA binding by ionic interactions is demonstrated by the effect of pH and of chloride ion concentration on the stoichiometry of FA.BLG complexes. At neutral pH in a low ionic strength buffer, one molecule of FA is bound per BLG monomer; this ratio decreases to ca. 0.5 per monomer in the presence of 200 mM NaCl. The polar heads of bound FA appear to be solvent accessible, and carboxyl resonances exhibit an NMR titration curve with an apparent pK(a) of 4.7(1).
Structure and stability of semiconductor tip apexes for atomic force microscopy (2009)

The short range force between the tip and the surface atoms, that is responsible for atomic-scale contrast in atomic force microscopy (AFM), is mainly controlled by the tip apex. Thus, the ability to image, manipulate and chemically identify single atoms in semiconductor surfaces is ultimately determined by the apex structure and its composition. Here we present a detailed and systematic study of the most common structures that can be expected at the apex of the Si tips used in experiments. We tackle the determination of the structure and stability of Si tips with three different approaches: (i) first principles simulations of small tip apexes; (ii) simulated annealing of a Si cluster; and (iii) a minima hopping study of large Si tips. We have probed the tip apexes by making atomic contacts between the tips and then compared force-distance curves with the experimental short range forces obtained with dynamic force spectroscopy. The main conclusion is that although there are multiple stable solutions for the atomically sharp tip apexes, they can be grouped into a few types with characteristic atomic structures and properties. We also show that the structure of the last atomic layers in a tip apex can be both crystalline and amorphous. We corroborate that the atomically sharp tips are thermodynamically stable and that the tip-surface interaction helps to produce the atomic protrusion needed to get atomic resolution.
Iron regulation of Shiga-like toxin expression in Escherichia coli is mediated by the fur locus (1987)

Shiga-like toxin is an iron-regulated cytotoxin quite similar to Shiga toxin from Shigella dysenteriae 1. The structural genes for Shiga-like toxin in Escherichia coli (sltA and sltB) appear to be transcribed as an operon from a promoter upstream of sltA. We used a gene fusion between the promoter and proximal portion of sltA with the gene for bacterial alkaline phosphatase to assess the regulation of toxin expression. Growth in low-iron conditions resulted in a 13- to 16-fold increase in alkaline phosphatase activity. In the presence of a null mutation in the fur locus, however, alkaline phosphatase activity was constitutively high regardless of the iron concentration. These data indicate negative regulation of the slt operon by the fur gene product. We used deletion analysis of the region upstream of the gene fusion to localize the promoter of the slt operon and to show that a region of DNA between the -35 and -10 boxes is necessary for iron regulation of slt expression. In this region, there is a 21-base-pair dyad repeat that is homologous to similar dyads in the promoter regions of three other fur-regulated genes. This region of dyad symmetry may represent an operator binding site for the Fur protein in the presence of iron.
mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes (2005)

The insulin-signaling pathway leading to the activation of Akt/protein kinase B has been well characterized except for a single step, the phosphorylation of Akt at Ser-473. Double-stranded DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM) gene product, integrin-linked kinase (ILK), protein kinase Calpha (PKCalpha), and mammalian target of rapamycin (mTOR), when complexed to rapamycin-insensitive companion of mTOR (RICTOR), have all been identified as playing a critical role in Akt Ser-473 phosphorylation. However, the apparently disparate results reported in these studies are difficult to evaluate, given that different stimuli and cell types were examined and that all of the candidate proteins have never been systematically studied in a single system. Additionally, none of these studies were performed in a classical insulin-responsive cell type or tissue such as muscle or fat. We therefore examined each of these candidates in 3T3-L1 adipocytes. In vitro kinase assays, using different subcellular fractions of 3T3-L1 adipocytes, revealed that phosphatidylinositol 3,4,5-trisphosphate-stimulated Ser-473 phosphorylation correlated well with the amount of DNA-PK, mTOR, and RICTOR but did not correlate with levels of ATM, ILK, and PKCalpha. PKCalpha was completely absent from compartments with Ser-473 phosphorylation activity. Although purified DNA-PK could phosphorylate a peptide derived from Akt that contains amino acid Ser-473, it could not phosphorylate full-length Akt2. Vesicles immunoprecipitated from low density microsomes using antibodies directed against mTOR or RICTOR had phosphatidylinositol 3,4,5-trisphosphate-stimulated Ser-473 activity that was sensitive to wortmannin but not staurosporine. In contrast, immunopurified low density microsome vesicles containing ILK could not phosphorylate Akt on Ser-473 in vitro. Small interference RNA knockdown of RICTOR, but not DNA-PK, ATM, or ILK, suppressed insulin-activated Ser-473 phosphorylation and, to a lesser extent, Thr-308 phosphorylation in 3T3-L1 adipocytes. Based on our cell-free kinase and small interference RNA results, we conclude that mTOR complexed to RICTOR is the Ser-473 kinase in 3T3-L1 adipocytes.
Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma. (1988)

Addition of IL-4 (1,000 U/ml) to either high or low concentrations of IL-2 augmented tumor-infiltrating lymphocytes (TIL) growth from human melanoma. Weekly restimulation with irradiated tumor cells in conjunction with IL-4 allowed enhanced growth of TIL. With low-dose IL-2 (10 U/ml) and IL-4, expanded TIL had little cytolytic activity against Daudi or allogeneic tumors. Further, IL-4 augmented the total lytic activity against autologous tumors in most cases. With high-dose IL-2 (1,000 U/ml), IL-4 addition decreased nonspecific killing activity against Daudi or allogeneic melanomas in many cases, and reciprocally augmented cytolytic activity against the autologous melanoma in many cases. This suggests the possible use of IL-4 in cancer therapy, especially in adoptive cellular immunotherapy using TIL or in conjunction with IL-2 administration.
Estudo sobre a ocorrência de micronúcleos e alterações nucleares em indivíduos com a Doença de Alzheimer (2012)

&lt;p&gt;A doença de Alzheimer (DA) é uma doença neurodegenerativa progressiva, de etiologia complexa, caracterizada clinicamente pela perda de memória e de outras funções cognitivas. Avanços na genética molecular têm indicado a existência de genes que conferem susceptibilidade, sendo o fator genético considerado como preponderante na etiopatogenia da DA. O teste de micronúcleos pode fornecer evidências de danos genotóxicos, que podem estar associadas à manifestação da doença de Alzheimer. Realizou-se esta investigação com o objetivo de verificar a predisposição à formação de micronúcleos e alterações nucleares em indivíduos com DA, tendo em vista contribuir para o conhecimento deste mal, considerado a principal causa de demência entre idosos. Para isto foram amostrados dez indivíduos afetados pela DA comparados a controles do mesmo sexo e faixa etária, e não portadores da doença. O teste de micronúcleo e alterações nucleares foi realizado em células esfoliadas da mucosa oral, com análise de 3000 células por indivíduo. Os dados foram tabulados e submetidos à análise estatística com a utilização do programa Graphpad. Foram observados micronúcleos em taxas não significativas e numero elevado de células em cariólise e cariorréxis, alterações nucleares associadas a fenômenos apoptóticos. A frequência alta destas alterações está de acordo com um epitélio envelhecido e pode ser um indicativo no estudo citopatológico da doença de Alzheimer.&lt;/p&gt;
Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUse of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteinsBeverly Peterkofsky and Robert DiegelmannCite this: Biochemistry 1971, 10, 6, 988–994Publication Date (Print):March 16, 1971Publication History Published online1 May 2002Published inissue 16 March 1971https://pubs.acs.org/doi/10.1021/bi00782a009https://doi.org/10.1021/bi00782a009research-articleACS PublicationsRequest reuse permissionsArticle Views473Altmetric-Citations1009LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Mutations which alter the level or structure of nsP4 can affect the efficiency of Sindbis virus replication in a host-dependent manner (1990)

Two mutants of Sindbis virus have been isolated which grow inefficiently at 34.5 degrees C in mosquito cells yet replicate normally in chicken embryo fibroblast cells at the same temperature. In addition, these mutants exhibit temperature-sensitive growth in both cell types and are RNA- at the nonpermissive temperatures (K.J. Kowal and V. Stollar, Virology 114:140-148, 1981). To clarify the basis of this host restriction, we have mapped the causal mutations for these temperature-dependent, host-restricted mutants. Functional mapping and sequence analysis of the mutant cDNAs revealed several mutations which mapped to the amino terminus of nsP4, the putative polymerase subunit of the viral RNA replicase. These mutations resulted in the following amino acid changes in nsP4: leucine to valine at residue 48, aspartate to glycine at residue 142, and proline to arginine at residue 187. Virus containing any of these mutations was restricted in its ability to replicate in mosquito but not chicken embryo fibroblast cells at 34.5 degrees C. In addition to its temperature-dependent, host-restricted phenotype, virus derived from one cDNA clone also exhibited decreased levels of nsP34 and nsP4 yet contained only a silent change in its genome. This C-to-U mutation occurred at nucleotide 5751, the first nucleotide after the opal termination codon separating nsP3 and nsP4. Our results suggest that this substitution decreases readthrough of the opal codon and diminishes production of nsP34 and nsP4. Such a decrease in synthesis rates might lead to levels of these products which are insufficient for viral RNA replication in mosquito cells at the higher temperature. This work provides the first evidence that nsP4 function can be strongly influenced by the host environment.
Hormonal Regulation of Cytochrome P450 Enzymes, Cholesterol Side-Chain Cleavage and 17α-Hydroxylase/C17 – 20 Lyase in Leydig Cells1 (1990)

Testosterone biosynthesis in Leydig cells is dependent on two cytochrome P450 enzymes, cholesterol side-chain cleavage (P450scc) and 17 alpha-hydroxylase/C17-20 lyase (P450(17 alpha]. The expression of these two enzymes is differentially regulated by LH acting via its second messenger, cyclic adenosine 3',5'-monophosphate (cAMP), and by specific steroid hormones. P450scc is constitutively expressed in normal mouse Leydig cells and in MA-10 tumor Leydig cells. Chronic cAMP stimulation increases the steady state levels of P450scc mRNA and de novo P450scc protein synthesis. In contrast, cAMP is obligatory for de novo synthesis of P450(17 alpha) in normal mouse Leydig cells; P450(17 alpha) synthesis ceases in the absence of luteinizing hormone or cAMP. MA-10 tumor Leydig cells do not express P450(17 alpha) even after treatment with cAMP. The amount of P450(17 alpha) in Leydig cells is negatively regulated by testosterone acting by two distinct mechanisms. At low concentrations, testosterone acts via the androgen receptor to repress cAMP-induced synthesis of P450(17 alpha), whereas at high concentrations this steroid increases the rate of degradation of the enzyme by an oxygen-mediated mechanism. Both constitutive and cAMP-induced synthesis of P450scc protein and steady state levels of mRNA are modulated by glucocorticoids. In normal mouse Leydig cells, glucocorticoids repress P450scc synthesis and steady state levels of P450scc mRNA, whereas glucocorticoids stimulate P450scc synthesis and levels of P450scc mRNA in the tumor Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)