gebhart/patrepeval huggingface dataset:
A highly conserved insulin-like growth factor-binding protein (IGFBP-5) is expressed during myoblast differentiation. (1993)

Insulin-like growth factor-binding proteins (IGFBPs) are a family of secreted proteins that bind insulin-like growth factors I and II (IGFs I and II) and are capable of modulating IGF actions on target cells. We have shown previously that C2 myoblasts secrete a single approximately 29-kDa IGFBP during their terminal differentiation (Tollefsen, S. E., Lajara, R., McCusker, R. H., Clemmons, D. R., and Rotwein, P. (1989) J. Biol. Chem. 264, 13810-13817). In this study, we have purified the protein from C2 cell-conditioned media by conventional and IGF-affinity chromatography, cloned its cDNA by PCR-based and traditional library screening, and identified it as mouse IGFBP-5. The resultant 5561 nucleotide cDNA encodes a 252-amino acid mature protein (predicted M(r) approximately 28,400) that is 97% identical to rat and human IGFBP-5. In differentiating C2 myoblasts and in F3 azamyoblasts the > 6-kilobase IGFBP-5 mRNA accumulates concomitantly with induction of myogen mRNA, an early marker of muscle differentiation. Ligand blot analysis shows that IGFBP-5 protein is secreted within 12 h of the onset of differentiation in these cells and that it is the only IGFBP produced in several fusing skeletal muscle cell lines. In vivo, IGFBP-5 transcripts are expressed in a variety of mouse tissues including striated muscle, but, unlike other IGFBPs, it is barely detectable in liver. IGFBP-5 is more conserved than other IGFBPs in mammals; its conserved structure and sequence also extends to non-mammalian vertebrates. Hybridization of a mouse BP5 coding region probe to RNA from several chicken and Xenopus tissues demonstrated similarly sized transcripts in these species. A partial Xenopus cDNA is identical in 38/45 deduced amino acids to the mammalian proteins. Identification of an IGF-binding protein that is produced during myoblast differentiation provides a model system in which to study the potential modulatory role of IGFBPs in development.
Exocytosis: Proteins and Perturbations (1996)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates (2020)

Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).
Interaction of retroviral nucleocapsid proteins with transfer RNAPhe: a lead ribozyme and 1H NMR study (1996)

In the initiation of reverse transcription in retroviruses, nucleocapsid (NC) protein accelerates the rate of annealing of transfer RNA replication primer to a complementary sequence on the genomic RNA. In this report, we have probed the conformational changes induced by HIV-1 NC protein and domain deletion mutants in a structurally well-characterized transfer RNA, yeast tRNAPhe, as a model for the natural primer. One molar equivalent of recombinant 71 amino acid HIV-1 nucleocapsid protein (NC 1-71) is sufficient to completely inhibit the Pb2(+)-ribozyme activity of tRNAPhe at 25 degrees C, pH 7.0 and 15 mM MgCl2, Zn2 HIV-1 NC proteins which lack one or both flexible terminal domains also inhibit the ribozyme activity. 1H NMR spectra acquired for Mg(2+)-tRNAPhe suggest that NC 1-71 and NC 12-55 (lacking residues 1-11 and 56-71) inhibit the lead-ribozyme activity by only modestly altering the active site region rather than inducing large-scale unfolding of the molecule. In the absence of Mg2+, the extent of destabilization of tRNAPhe is greater but appears to be confined to internal regions of the acceptor and T psi C helices, as evidenced by the selectively enhanced exchange rates for imino protons associated with these base pairs. These findings show that NC destabilizes the folded form of tRNAPhe and by extension, other complex RNAs, in tertiary and secondary structural regions most susceptible to thermally-induced denaturation.
Antimalarial Xanthones fromGarcinia cowa (1998)

Five xanthones from the bark of Garcinia cowa, namely 7-O-methylgarcinone E (1), cowanin (2), cowanol (3), cowaxanthone (4), and beta-mangostin (5), were found to possess in vitro antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to 3.00 micrograms/ml. Complete 1H- and 13C-NMR assignments of these compounds are also reported.
Estrogen and Progesterone Regulation of Proliferation, Migration, and Loss in Different Target Cells of Rabbit Uterine Epithelium* (1984)

We have explored the possibility that estrogens and progesterone could have different target uterine cell populations according to their cell cycle stage and localization in glands vs. lumen. Experiments were carried out in which rabbits were injected with [3H]thymidine for 3 days to label nuclei of dividing cells, then either 17 beta-estradiol, progesterone, or vehicle were administered. 17 beta-Estradiol induced a decrease in the percentage of cells with labeled nuclei or labeling index of either luminal or glandular epithelium. Since this steroid has been shown to have a significant proliferative effect on glands, the data suggest that its effect is exerted on unlabeled quiescent cells, which are then recruited into the cell cycle. Progesterone, on the other hand, was found to induce a significant increase in labeling index of both luminal and glandular epithelium. Therefore, it is concluded that dividing cells are a target for this hormone. Analysis of the number of nuclear grains according to cell location in luminal vs. glandular epithelia and the effect of hormone administration confirmed that each ovarian hormone acts on different target cell populations. Short and long term administration of estrogens resulted in a larger internal circumference of the uterus due to an increase in the number of luminal cells, whereas the number of glands and glandular cells per section did not appear to change. These findings, in combination with previous research, suggest that endometrial gland cells migrate towards the lumen and estrogen administration decreases the rate of cell loss in the luminal epithelium. The concept of cell migration is supported by experiments in which single administration of [3H]thymidine to rabbits was followed by determination at different times of the geographical distribution of cells with labeled nuclei. There was observed, as a function of time, a decrease in the number of labeled cells in the bottom of the glands with a concomitant increase in the same parameter in the upper part of the glands and luminal epithelia. Estradiol administration changed these kinetics.
Aberrant Promoter Methylation of Multiple Genes during Pathogenesis of Bladder Cancer (2008)

Our results indicate that the methylation profile of novel genes in bladder cancers correlates with clinicopathologic features of poor prognosis and is an age-related phenomenon.
Nanostructured Vanadium Oxide Electrodes for Enhanced Lithium‐Ion Intercalation (2006)

Abstract This article summarizes our most recent studies on improved Li + ‐intercalation properties in vanadium oxides by engineering the nanostructure and interlayer structure. The intercalation capacity and rate are enhanced by almost two orders of magnitude with appropriately fabricated nanostructures. Processing methods for single‐crystal V 2 O 5 nanorod arrays, V 2 O 5 · n H 2 O nanotube arrays, and Ni/V 2 O 5 · n H 2 O core/shell nanocable arrays are presented; the morphologies, structures, and growth mechanisms of these nanostructures are discussed. Electrochemical analysis demonstrates that the intercalation properties of all three types of nanostructure exhibit significantly enhanced storage capacity and rate performance compared to the film electrode of vanadium pentoxide. Addition of TiO 2 to orthorhombic V 2 O 5 is found to affect the crystallinity, microstructure, and possible interaction force between adjacent layers in V 2 O 5 , and subsequently leads to enhanced Li + ‐intercalation properties in V 2 O 5 . The amount of water intercalated in V 2 O 5 is found to have a significant influence on the interlayer spacing and electrochemical performance of V 2 O 5 · n H 2 O. A systematic electrochemical study has demonstrated that the V 2 O 5 ·0.3 H 2 O film has the optimal water content and exhibits the best Li + ‐intercalation performance.
Hair follicle dermal cells repopulate the mouse haematopoietic system (2002)

Skin and hair follicle stem cell biology is the focus of increasing interest, not least because the adult hair follicle has well defined dermal and epithelial populations that display distinct developmental properties. Recent evidence suggests that a number of adult cell populations have much broader stem cell capabilities than previously thought. To examine whether this applied to the hair follicle, and with a view to developing the follicle as a stem cell model system we investigated whether adult hair follicles were capable of demonstrating haematopoietic stem cell activity. To investigate haematopoietic activity in hair follicles we first used in vitro haematopoietic colony assays. This demonstrated that rodent hair follicle end bulbs as well as micro-dissected dermal papilla and dermal sheath cells actively produced cells of erythroid and myeloid lineages but that follicle epithelial cells did not. As a more stringent test, we then transplanted cultured dermal papilla or dermal sheath cells from transgenically marked donor mice into lethally irradiated recipient mice and observed multi-lineage haematopoietic reconstitution when assayed at intervals of up to one year. Colony assays from bone marrow of primary recipients revealed that over 70% of clonogenic precursors were derived from donor hair follicle cells. When bone marrow from primary mice was harvested and used to repopulate secondary myeloablated recipients, multi-lineage haematopoietic engraftment was observed. Our data show that dermal but not epidermal compartments of the adult hair follicle have much broader stem cell activities than previously described. Although the treatment for many forms of blood disorder, such as leukemia, often requires transplantation of haematopoietic stem cells (HSC), their availability can be rate limiting. Given its easy accessibility, our identification of the hair follicle as a source of extramedullary haematopoietic stem cell activity makes it an attractive potential source for blood stem cell therapeutics and highlights its value as a model system in adult stem cell biology.
Long-term effects of nonpeptide vasopressin V2antagonist OPC-31260 in heart failure in the rat (1998)

The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V2 and V1a receptors, respectively. The effect of long-term V2 receptor (V2R) blockade using OPC-31260 was assessed in a rat model of postinfarction-induced CHF. Rats underwent coronary artery ligation or sham operation and were treated for 6 mo with oral OPC-31260 (10 mg . kg-1 . day-1) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic function, increased cardiac and lung weight, and elevated plasma atrial natriuretic peptide; plasma AVP and plasma renin activity were not increased. Chronic V2R blockade increased urine volume (P < 0.01) and decreased urine osmolality (P < 0.01) but had no natriuretic effects. V2R blockade did not activate the renin-angiotensin system but increased plasma AVP in CHF (P < 0.01). V2R blockade did not influence cardiac remodeling, cardiac function, or survival. These results suggest that AVP plays a major role in water retention through the renal V2R in a rat model of CHF. V2R blockade using OPC-31260 may represent an alternative to standard diuretic therapy in the management of water retention that characterizes heart failure.
Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications (2019)

Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.
Receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes: receptor pathway. (1986)

Substantial amounts of epidermal growth factor (EGF) are cleared from the circulation by hepatocytes via receptor-mediated endocytosis and subsequently degraded within lysosomes. We have used a combined biochemical and morphological approach to examine the fate of the receptor after exposure to EGF. Polyclonal antibodies were prepared against the purified receptor and their specificity established by immunoprecipitation and immunoblotting techniques. The EGF receptor was then localized by immunofluorescence and immunoperoxidase techniques and quantified on immunoblots. In untreated livers, EGF receptor was restricted to the sinusoidal and lateral surfaces of hepatocytes. 2-4 min after exposure of cells to EGF, the receptor was found in small vesicles (i.e., coated vesicles) as well as larger vesicles and tubules at the cell periphery. By 15 min the receptor was found in multivesicular endosomes located near bile canaliculi. Exposure of hepatocytes to EGF also resulted in a rapid loss of receptor protein from total liver homogenates and a decrease in its half-life from 8.7 h in control livers to 2.5 h. This EGF-induced loss of receptors was not observed when lysosomal proteinases were inhibited by leupeptin or when endosome/lysosome fusion was prevented by low temperature (16 degrees C). In the presence of leupeptin, receptor could be detected in structures identified as lysosomes using acid-phosphatase cytochemistry. All these results suggested rapid internalization of EGF receptors in response to ligand and degradation within lysosomes. However, four times more ligand was degraded at 8 h than the number of high-affinity (Kd of 8-15 nM) EGF-binding sites lost, suggesting either (a) high-affinity receptors were recycled, and/or (b) more than 300,000 receptors were available for EGF uptake. We identified and characterized a latent pool of approximately 300,000 low-affinity receptors (Kd approximately 200 nM) that could be separated on sucrose gradients from the plasma membrane pool of approximately 300,000 high-affinity receptors (Kd of 8-15 nM). Despite the differences in their binding affinities, the high- and low-affinity receptors appeared to be structurally identical and were both EGF-dependent protein kinases. In addition, the dynamics of the low-affinity receptors were consistent with a functional role in EGF uptake and delivery to lysosomes.
Mesothelial Differentiation as Reflected by Differential Gene Expression (2003)

Human mesothelial cells obtained from benign effusions retain their proliferative capacity and grow uniformly either with a fibroblastic or epithelioid morphology in vitro. These cultures therefore provide a model for the process of mesothelial differentiation in vivo. To study this differentiation, we isolated differentially expressed genes obtained by suppression subtractive hybridization. Of the nine genes found to be overexpressed in fibroblastic mesothelial cells, three are matrix-associated (integrin alpha5, collagen binding protein 2, human cartilage glycoprotein 39), whereas the others are associated with a proliferative cell type (14-3-3 epsilon, plexin B2, N33, and three genes encoding ribosomal elements). Seven of the eight genes upregulated in the epithelioid phenotype are related rather to specialized functions, such as metabolism (aldose reductase, lecithin:cholesterol acyltransferase, ATPase 6), cytoskeletal composition (cytokeratins 7 and 8), and regulation of differentiation (granulin, annexin II). Immunohistochemistry with available antibodies to six of the differentially expressed gene products confirmed the differences also in pleural tissues, where submesothelial cells displayed the fibroblastic markers, whereas surface cells displayed the epithelioid markers. In summary, this approach revealed a pattern of genes coordinately regulated during mesothelial differentiation and suggests that mesothelium may regenerate also by recruiting cells from the submesothelial layer. Some of the gene products may also be useful markers for differentiation and activation in serosal tissues.
DNA sequencing with dye-labeled terminators and T7 DNA polymerase: effect of dyes and dNTPs on incorporation of dye-terminators and probability analysis of termination fragments (1992)

The incorporation of fluorescently labeled dideoxynucleotides by T7 DNA polymerase is optimized by the use of Mn2+, fluorescein analogs and four 2'-deoxyribonucleoside 5'-O-(1-thiotriphosphates) (dNTP alpha S's). The one-tube extension protocol was tested on single-stranded templates, as well as PCR fragments which were made single-stranded by digestion with T7 gene 6 exonuclease. Dye primer sequencing using four dNTP alpha S's was shown to give uniform termination patterns which were comparable to four dNTPs. Efficiency of the polymerase also appeared to improve with the dNTP alpha S's. A mathematical model was developed to predict the pattern of termination based on enzyme activity and ratios of ddNTP/dNTPs. This method can be used to optimize sequencing reactions and to estimate enzyme discrimination constants of chain terminators.
Quantification of AC electromagnetic tracking system accuracy in a CT scanner environment (2007)

The purpose of this study was to quantify the effects of a computed tomography (CT) scanner environment on the positional accuracy of an AC electromagnetic tracking system, the second generation NDI Aurora. A three-axis positioning robot was used to move an electromagnetically tracked needle above the CT table throughout a 30cm by 30cm axial plane sampled in 2.5cm steps. The corresponding position data was captured from the Aurora and was registered to the positioning system data using a rigid body transformation minimizing the least squares L2-norm. Data was sampled at varying distances from the CT gantry (three feet, two feet, and one foot) and with the CT table in a nominal position and lowered by 10cm. A coordinate system was defined with the x axis normal to the CT table and the origin at the center of the CT table, and the z axis spanning the table in the lateral direction with the origin at the center of the CT table. In this coordinate system, the positional relationships of each sampled point, the CT table, and the Aurora field generator are clearly defined. This allows error maps to be displayed in accurate spatial relationship to the CT scanner as well as to a representative patient anatomy. By quantifying the distortions in relation to the position of CT scanner components and the Aurora field generator, the optimal working field of view and recommended guidelines for operation can be determined such that targeting inside human anatomy can be done with reasonable expectations of desired performance.
A working guide to boosted regression trees (2008)

1. Ecologists use statistical models for both explanation and prediction, and need techniques that are flexible enough to express typical features of their data, such as nonlinearities and interactions. 2. This study provides a working guide to boosted regression trees (BRT), an ensemble method for fitting statistical models that differs fundamentally from conventional techniques that aim to fit a single parsimonious model. Boosted regression trees combine the strengths of two algorithms: regression trees (models that relate a response to their predictors by recursive binary splits) and boosting (an adaptive method for combining many simple models to give improved predictive performance). The final BRT model can be understood as an additive regression model in which individual terms are simple trees, fitted in a forward, stagewise fashion. 3. Boosted regression trees incorporate important advantages of tree-based methods, handling different types of predictor variables and accommodating missing data. They have no need for prior data transformation or elimination of outliers, can fit complex nonlinear relationships, and automatically handle interaction effects between predictors. Fitting multiple trees in BRT overcomes the biggest drawback of single tree models: their relatively poor predictive performance. Although BRT models are complex, they can be summarized in ways that give powerful ecological insight, and their predictive performance is superior to most traditional modelling methods. 4. The unique features of BRT raise a number of practical issues in model fitting. We demonstrate the practicalities and advantages of using BRT through a distributional analysis of the short-finned eel (Anguilla australis Richardson), a native freshwater fish of New Zealand. We use a data set of over 13 000 sites to illustrate effects of several settings, and then fit and interpret a model using a subset of the data. We provide code and a tutorial to enable the wider use of BRT by ecologists.
MIP-3α neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice (2007)

A characteristic feature of human inflammatory bowel disease, particularly Crohn's disease, is the presence of activated CD4(+) T cells. Recently, we have shown that colonic epithelial cell production of macrophage inflammatory protein (MIP)-3alpha, a CD4 T cell-directed chemokine, is elevated in inflammatory bowel disease. However, the functional relevance of MIP-3alpha production during intestinal inflammation is poorly understood. The aim of this study was to determine whether MIP-3alpha production is increased during murine 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and to examine the effect of anti-MIP-3alpha neutralizing monoclonal antibody administration in this model. We found that the administration of TNBS significantly increased colonic MIP-3alpha protein levels in Balb/c mice. Consistent with this, a marked increase in the number of CCR6-bearing lamina propria CD4(+) and CD8(+) T cells was also observed in TNBS-treated animals. Treatment of mice with an anti-MIP-3alpha neutralizing monoclonal antibody significantly reduced TNBS-mediated increases in colonic weight-to-length ratio, mucosal ulceration, histological damage, and myeloperoxidase activity. TNBS-mediated increases in the number of CCR6-bearing lamina propria T cells were also substantially reduced by anti-MIP-3alpha neutralizing monoclonal antibody treatment. Taken together, our findings indicate that blockade of MIP-3alpha bioactivity can significantly reduce TNBS-mediated colonic injury and T cell recruitment, suggesting a role for this chemokine in the pathophysiology of intestinal inflammation.