gebhart/patrepeval huggingface dataset:
Ulcerative colitis: responding to the challenges. (2007)

Aminosalicylates are the first-line therapy for patients with mild to moderate active ulcerative colitis. Treatment should start at dosages of 4.8 g per day of the active 5-aminosalicylate moiety, rather than starting at a lower dosage and increasing if treatment fails. Infliximab has been shown to be effective and is now approved by the US Food and Drug Administration for the treatment of moderately to severely active ulcerative colitis in patients who have had an inadequate response to conventional therapy.
Distribution of immunoglobulin G receptors in the small intestine of the young rat. (1980)

Conjugates of horseradish peroxidase (HRP) and immunoglobulin G (IgG) were used to map the distribution of cell surface receptors that can bind IgG at 0 degrees C within the small intestine of 10-12-d-old rats. Luminal receptors are present only within the duodenum and proximal jejunum. In these locations, receptors are limited to absorptive cells that line the upper portion of individual villi. Near villus tips, receptors are relatively evenly distributed over the entire luminal plasmalemma. In the midregion of villi, receptors are unevenly distributed over the luminal surface. Receptors (a) specifically bind rat and rabbit IgG, (b) recognize the Fc portion of the immunoglobulins, and (c) bind at pH 6.0 but not pH 7.4. To determine whether IgG receptors are confined to the luminal portion of the plasmalemma, intact epithelial cells were isolated from the proximal intestine of 10-12-d-old rats and incubated with HRP conjugates at 0 degree C. The specific binding of rat IgG-HRP to cells at pH 6.0 indicates that IgG receptors, which are functionally similar to those found on the luminal surface, are also present over the entire abluminal surface of absorptive cells. These results are consistent with the transport of IgG to the abluminal plasma membrane in the form of IgG-receptor complexes on the surface of vesicles. Exposure of these complexes to the serosal plasma, which is presumably at pH 7.4, would cause release of IgG from the receptors. To assess possible inward movement of vesicles from the abluminal surface after discharge of IgG, intravenously injected HRP was used as a space-filling tracer in the serosal plasma. HRP could be visualized within the coated and tubular vesicles responsible for transport of IgG in the opposite direction. These vesicles may, therefore, provide a pathway whereby receptors shuttle between the luminal and abluminal surfaces of cells.
Enhancement of recA protein-promoted DNA strand exchange activity by volume-occupying agents. (1992)

To investigate the in vivo effects of macromolecular crowding we examined the effect of inert macromolecules such as polyvinyl alcohol and polyethylene glycol on the in vitro activity of recA protein. The addition of either of these volume-occupying agents enables recA protein to promote homologous pairing and exchange of DNA strands at an otherwise nonpermissive magnesium ion concentration. In the presence of these macromolecules, both the rate of recA protein association with single-stranded DNA (ssDNA) and the steady-state affinity of recA protein for ssDNA are increased. Consequently, the ability of recA protein to compete with ssDNA-binding protein (SSB protein) is enhanced, and the inhibitory effects of SSB protein on the formation of recA protein-ssDNA presynaptic complexes are eliminated. Because the ability of recA protein to bind to ssDNA-containing secondary structures is also enhanced in volume-occupied solution, joint molecule formation is not greatly reduced when SSB protein is omitted from the reaction. Thus, increased recA protein interactions with ssDNA contribute to enhanced presynaptic complex formation. In addition, polyvinyl alcohol and polyethylene glycol must also affect another property of recA protein, i.e. self-association, which is required for synapsis and DNA strand exchange. Our examination of DNA strand exchange in the presence of volume-occupying agents helps to reconcile the requirement for elevated magnesium ion concentrations in recA protein-promoted recombination reactions in vitro, with a presumably low magnesium ion concentration in vivo.
Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD (2016)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined. Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated. Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis. We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens. WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence. Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro. Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo. Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD. We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy.
Cell membrane electrical charge investigations by silicon nanowires incorporated field effect transistor (SiNWFET) suitable in cancer research (2013)

Obtaining biocompatible skein shaped silicon nanowires covered field-effect transistors (SiNWFETs) is reported. Such structures are formed by the growth of Si nanowires on top of the polysilicon gate terminal of a n-MOSFET in three-probe top-gate geometry for cells membrane electrical charge detection suitable in biological applications such as cancer investigations. We observe that electro-negativity increment of metastatic cells outer membrane restricts the drain current of bioFET. SiNWFET is proposed to be used covered with skein SiNW. Different invasive grades of colon cancers (HT29 and SW48) owing to their dissimilar negative charge production, affect the electrical response of the device.
Therapeutic FGF19 promotes HDL biogenesis and transhepatic cholesterol efflux to prevent atherosclerosis (2019)

Fibroblast growth factor (FGF)19, an endocrine hormone produced in the gut, acts in the liver to control bile acid synthesis. NGM282, an engineered FGF19 analog, is currently in clinical development for treating nonalcoholic steatohepatitis. However, the molecular mechanisms that integrate FGF19 with cholesterol metabolic pathways are incompletely understood. Here, we report that FGF19 and NGM282 promote HDL biogenesis and cholesterol efflux from the liver by selectively modulating LXR signaling while ameliorating hepatic steatosis. We further identify ABCA1 and FGF receptor 4 as mediators of this effect, and that administration of a HMG-CoA reductase inhibitor or a blocking antibody against proprotein convertase subtilisin/kexin type 9 abolished FGF19-associated elevations in total cholesterol, HDL cholesterol (HDL-C), and LDL cholesterol in <i>db/db</i> mice. Moreover, we show that a constitutively active MEK1, but not a constitutively active STAT3, mimics the effect of FGF19 and NGM282 on cholesterol change. In dyslipidemic <i>Apoe</i><sup>-/-</sup> mice fed a Western diet, treatment with NGM282 dramatically reduced atherosclerotic lesion area in aortas. Administration of NGM282 to healthy volunteers for 7 days resulted in a 26% increase in HDL-C levels compared with placebo. These findings outline a previously unrecognized role for FGF19 in the homeostatic control of cholesterol and may have direct impact on the clinical development of FGF19 analogs.
Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis (2004)

The results suggest that A. vaginae may be an important component of the complex bacterial ecology that constitutes abnormal vaginal flora. This organism could play a role in treatment failure if further studies confirm it is consistently metronidozole resistant.
Spatial Transformations for Eye–Hand Coordination (2004)

Eye-hand coordination is complex because it involves the visual guidance of both the eyes and hands, while simultaneously using eye movements to optimize vision. Since only hand motion directly affects the external world, eye movements are the slave in this system. This eye-hand visuomotor system incorporates closed-loop visual feedback but here we focus on early feedforward mechanisms that allow primates to make spatially accurate reaches. First, we consider how the parietal cortex might store and update gaze-centered representations of reach targets during a sequence of gaze shifts and fixations. Recent evidence suggests that such representations might be compared with hand position signals within this early gaze-centered frame. However, the resulting motor error commands cannot be treated independently of their frame of origin or the frame of their destined motor command. Behavioral experiments show that the brain deals with the nonlinear aspects of such reference frame transformations, and incorporates internal models of the complex linkage geometry of the eye-head-shoulder system. These transformations are modeled as a series of vector displacement commands, rotated by eye and head orientation, and implemented between parietal and frontal cortex through efficient parallel neuronal architectures. Finally, we consider how this reach system might interact with the visually guided grasp system through both parallel and coordinated neural algorithms.
Carbethoxynitrene (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbethoxynitreneWalter. Lwowski, Tom J. Maricich, and Thomas W. MattinglyCite this: J. Am. Chem. Soc. 1963, 85, 8, 1200–1202Publication Date (Print):April 1, 1963Publication History Published online1 May 2002Published inissue 1 April 1963https://doi.org/10.1021/ja00891a039RIGHTS & PERMISSIONSArticle Views212Altmetric-Citations76LEARN 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 InReddit PDF (348 KB) Get e-Alerts Get e-Alerts
Production of ethanol by Clostridium thermosaccharolyticum: I. Effect of cell recycle and environmental parameters (1989)

The direct microbial conversion (DMC) process for the production of ethanol from lignocellulosic biomass is limited by low volumetric ethanol production rates due to the low cell densities of Clostridium thermosaccharolyticum which is a key organism for ethanol production in this process. Hence, this study focuses on the use of a continuous- culture cell recycle system to improve the volumetric ethanol productivity and yield of the fermentation of xylose by C. thermosaccharolyticum. Early experiments with the continuous-culture cell recycle system showed a two-fold improvement in volumetric ethanol productivity. However, the ethanol yield at the higher dilution rates suffered because of the large amount of lactate produced. The manipulation of two environmental parameters--iron concentration in the nutrient medium and the N(2) purge rate of the fermentor headspace--allowed a dramatic reduction in the lactate production and a simultaneous improvement in the ethanol titer and yield. Under the improved conditions of increased iron concentration (12.5 mg/L FeSO(4) x 7H(2)O) and decreased N(2) purge rate (0.1 L/min), a continuous culture of C. thermosaccharolyticum operating at a dilution rate of 0.24 h(-1) and 50% cell recycle produced 8.6 g/L ethanol and less than 1 g/L each of acetate and lactate. The volumetric ethanol productivity was 2.2 g/L/h, which is 8 times larger than obtained for a continuous culture operated with no cell recycle and the same specific growth rate.
Bcl‐3 is an interleukin‐1–responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene (2002)

These data define a new role for Bcl-3 in joint cells as an IL-1beta-responsive early gene involved in cell-mediated cartilage remodeling. Our findings implicate Bcl-3 as an important contributor to chronic inflammatory disease states, such as osteoarthritis and rheumatoid arthritis.
ONCOLYSIS BY CLOSTRIDIA. II. EXPERIMENTS ON A TUMOR SPECTRUM WITH A VARIETY OF CLOSTRIDIA IN COMBINATION WITH HEAVY METAL. (1964)

The oncolytic effects of intravenously injected spores of Cl. butyricum (M-55) have been tested in a series of mouse and rat tumors. The results depended on the strain of tumor used, the age and thereby the size of the tumor, and the species of animal. Since even in the most favorable circumstances the oncolysis is rarely complete, it was attempted to improve the results by the simultaneous application of a series of metabolic products of clostridia and of tumors. The results were essentially negative.

It was observed that porphyrins present in the tumor or formed during oncolysis had a deleterious effect on the growth of clostridia. If the activity of porphyrins was blocked by the parenteral or local application of heavy metals, particularly the proper iron compounds, a faster and more extensive lysis could be obtained. This was true not only for tumors which had only a moderate sensitivity to the clostridia but also for smaller tumors of sensitive strains. Oncolysis by a series of nonpathogenic strains of clostridia was tested on three different mouse tumors, and in each instance the effect could be enhanced by the simultaneous parenteral treatment with an iron dextran complex. These observations open a way for improvement of results of spore therapy that so far were not sufficiently satisfying.
Phosphotyrosine-Dependent Interaction of SHC and Insulin Receptor Substrate 1 with the NPEY Motif of the Insulin Receptor via a Novel Non-SH2 Domain (1995)

The SHC proteins have been implicated in insulin receptor (IR) signaling. In this study, we used the sensitive two-hybrid assay of protein-protein interaction to demonstrate that SHC interacts directly with the IR. The interaction is mediated by SHC amino acids 1 to 238 and is therefore independent of the Src homology 2 domain. The interaction is dependent upon IR autophosphorylation, since the interaction is eliminated by mutation of the IR ATP-binding site. In addition, mutational analysis of the Asn-Pro-Glu-Tyr (NPEY) motif within the juxtamembrane domain of the IR showed the importance of the Asn, Pro, and Tyr residues to both SHC and IR substrate 1 (IRS-1) binding. We conclude that SHC interacts directly with the IR and that phosphorylation of Tyr-960 within the IR juxtamembrane domain is necessary for efficient interaction. This interaction is highly reminiscent of that of IRS-1 with the IR, and we show that the SHC IR-binding domain can substitute for that of IRS-1 in yeast and COS cells. We identify a homologous region within the IR-binding domains of SHC and IRS-1, which we term the SAIN (SHC and IRS-1 NPXY-binding) domain, which may explain the basis of these interactions. The SAIN domain appears to represent a novel motif which is able to interact with autophosphorylated receptors such as the IR.
Reduced Frequency of HLA DRB1*03‐DQB1*02 in Children with Type 1 Diabetes Associated with Enterovirus RNA (2003)

Enteroviruses have been associated with type 1 diabetes mellitus (T1DM), but it is unclear whether there is a distinct disease subtype. Plasma and stool samples from 206 consecutively diagnosed children and 160 healthy control children were analyzed by reverse-transcription polymerase chain reaction for the RNA of 60 enteroviruses. More children with diabetes tested positive for enterovirus RNA (30% vs. 4%; odds ratio, 11.1; 95% confidence interval, 4.7-25.7; P<.001). Enterovirus 71 was detected in 25% of children; these were temporally associated with outbreaks in Southeast Asia and Australia. Fewer children with the diabetes-associated human leukocyte antigen DRB1*03-DQB1*02 genotype tested positive for enterovirus RNA (P=.02). More children presenting with severe diabetic ketoacidosis (pH, <7.1) tested positive for enterovirus RNA (P=.04). These results suggest that there is a subgroup of patients with T1DM, who are at low genetic risk, in whom enteroviruses contribute to diabetes onset.
Regulation of LFA-1 avidity in human B cells. Requirements for dephosphorylation events for high avidity ICAM-1 binding (1992)

Regulation of the avidity of LFA-1 (CD11a/CD18, alpha L beta 2) for its ligand ICAM-1 (CD54) was studied in human B cells by evaluating the effects of a phorbol ester, anti-IgM antibodies, staurosporine, and okadaic acid. We monitored changes in LFA-1 avidity by quantifying binding of cells to an immobilized rICAM-1 fusion protein. In this assay, the protein kinase C-activating phorbol ester PDB and anti-IgM antibodies, as well as the protein kinase inhibitor, staurosporine, were able to induce LFA-1-dependent binding to ICAM-1. This demonstrates that the high avidity state of LFA-1 can be induced by a protein kinase C-dependent and by a protein kinase C-independent pathway. Furthermore, treatment of the cells with the protein phosphatase inhibitor, okadaic acid, inhibited binding to ICAM-1. Treatment with staurosporine before addition of okadaic acid not only induced enhanced binding of cells to ICAM-1, but also dramatically reduced the ability of okadaic acid to inhibit binding. These results suggest a critical role for a protein phosphatase in inducing the high avidity state of LFA-1 as well as a role for a protein kinase in inducing the low avidity state of LFA-1.
Dissecting Colony Development ofNeurospora crassaUsing mRNA Profiling and Comparative Genomics Approaches (2008)

Colony development, which includes hyphal extension, branching, anastomosis, and asexual sporulation, is a fundamental aspect of the life cycle of filamentous fungi; genetic mechanisms underlying these phenomena are poorly understood. We conducted transcriptional profiling during colony development of the model filamentous fungus Neurospora crassa, using 70-mer oligonucleotide microarrays. Relative mRNA expression levels were determined for six sections of defined age excised from a 27-h-old N. crassa colony. Functional category analysis showed that the expression of genes involved in cell membrane biosynthesis, polar growth, and cellular signaling was enriched at the periphery of the colony. The relative expression of genes involved in protein synthesis and energy production was enriched in the middle section of the colony, while sections of the colony undergoing asexual development (conidiogenesis) were enriched in expression of genes involved in protein/peptide degradation and unclassified proteins. A cross-examination of the N. crassa data set with a published data set of Aspergillus niger revealed shared patterns in the spatiotemporal regulation of gene orthologs during colony development. At present, less than 50% of genes in N. crassa have functional annotation, which imposes the chief limitation on data analysis. Using an evolutionary approach, we observed that the expression of phylogenetically conserved groups of genes was enriched in the middle section of an N. crassa colony whereas expression of genes unique to euascomycete species and of N. crassa orphan genes was enriched at the colony periphery and in the older, conidiating sections of a fungal colony.
Amino acid sequences of α-helical segments from S-carboxymethylkerateine-A. Tryptic and chymotryptic peptides from a type-II segment (1978)

1. Amino acid-sequence studies were done on a peptide of mol.wt. approx. 12500 that was isolated from the highly helical fragments obtained by partial chymotryptic digestion of the low-sulphur proteins (S-carboxymethylkerateine-A) from wool. 2. The peptides obtained by tryptic and chymotryptic digestion of this large peptide were separated by ion-exchange chromatography on DEAE-cellulose at pH8.5 with an (NH4)(2)CO(3) concentration gradient and, where necessary, purified further by paper electrophoresis. 3. Determination of the sequences of many of these peptides showed that a high proportion of the cationic residues occurs in pairs. 4. Although two of the four S-carboxymethylcysteine residues are located in what appears to be a non-helical region near the N-terminus the other two S-carboxymethylcysteine residues occur in or near sequences suggesting a helical conformation. 5. Some peptides were obtained, in low yields, that appeared to be homologues of more major ones. These suggest either homologies in the helical portions of the low-sulphur proteins or the presence of closely related amino acid sequences in helical regions of completely different origins. 6. A partial sequence of the complete peptide is proposed.
Nitric Oxide-Releasing Cyclodextrins (2018)

A series of secondary amine-modified cyclodextrin (CD) derivatives was synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6-2.4 μmol/mg) and release half-lives (0.7-4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donors. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa, a Gram-negative pathogen, with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated heptasubstituted CD derivatives exhibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug-releasing therapeutic.