gebhart/patrepeval huggingface dataset:
Taste Receptors in the Gastrointestinal Tract II.l-Amino acid sensing by calcium-sensing receptors: implications for GI physiology (2006)

The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for several key nutrients, notably Ca2+ ions and L-amino acids, and is expressed abundantly throughout the gastrointestinal tract. While its role as a Ca2+ ion sensor is well recognized, its physiological significance as an L-amino acid sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion is only now coming to light. This review focuses on the CaR's amino acid sensing properties at both the molecular and cellular levels and considers new and putative physiological roles for the CaR in the amino acid-dependent regulation of gut hormone secretion, epithelial transport, and satiety.
Dehydration of (R)-2-hydroxyacyl-CoA to enoyl-CoA in the fermentation of α-amino acids by anaerobic bacteria (2004)

Several clostridia and fusobacteria ferment alpha-amino acids via (R)-2-hydroxyacyl-CoA, which is dehydrated to enoyl-CoA by syn-elimination. This reaction is of great mechanistic interest, since the beta-hydrogen, to be eliminated as proton, is not activated (pK 40-50). A mechanism has been proposed, in which one high-energy electron acts as cofactor and transiently reduces the electrophilic thiol ester carbonyl to a nucleophilic ketyl radical anion. The 2-hydroxyacyl-CoA dehydratases are two-component systems composed of an extremely oxygen-sensitive component A, an activator, and component D, the actual dehydratase. Component A, a homodimer with one [4Fe-4S]cluster, transfers an electron to component D, a heterodimer with 1-2 [4Fe-4S]clusters and FMN, concomitant with hydrolysis of two ATP. From component D the electron is further transferred to the substrate, where it facilitates elimination of the hydroxyl group. In the resulting enoxyradical the beta-hydrogen is activated (pK14). After elimination the electron is handed-over to the next incoming substrate without further hydrolysis of ATP. The helix-cluster-helix architecture of component A forms an angle of 105 degrees, which probably opens to 180 degrees upon binding of ATP resembling an archer shooting arrows. Therefore we designated component A as 'Archerase'. Here, we describe 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans, Clostridium symbiosum and Fusobacterium nucleatum, 2-phenyllactate dehydratase from Clostridium sporogenes, 2-hydroxyisocaproyl-CoA dehydratase from Clostridium difficile, and lactyl-CoA dehydratase from Clostridium propionicum. A relative of the 2-hydroxyacyl-CoA dehydratases is benzoyl-CoA reductase from Thauera aromatica. Analogous but unrelated archerases are the iron proteins of nitrogenase and bacterial protochlorophyllide reductase. In anaerobic organisms, which do not oxidize 2-oxo acids, a second energy-driven electron transfer from NADH to ferredoxin, the electron donor of component A, has been established. The transfer is catalysed by a membrane-bound NADH-ferredoxin oxidoreductase driven by an electrochemical Na(+)-gradient. This enzyme is related to the Rnf proteins involved in Rhodobacter capsulatus nitrogen fixation.
A Decade of Right Liver Adult-to-Adult Living Donor Liver Transplantation (2008)

High midterm survivals were achieved by reduction of hospital mortality through accumulation of experience and transplanting recipients with low chance of recurrence of HCC. RLDLT could be considered as a legitimate alternative to DDLT.
Effect of rejuvenation and frozenstorage on 42‐day‐old AS‐1 RBCs (2001)

Forty-two-day-old AS-1 RBCs that have been rejuvenated and then frozen have more than 75 percent viability and normal oxygen delivery function. Rejuvenation of RBCs does not introduce additional safety hazards to blood transfusion.
A Comparison of Multiple Urine Markers for Interstitial Cystitis (2002)

This study confirmed several previously reported urine alterations in interstitial cystitis, including increased anti-proliferative factor, epidermal growth factor, IGF binding protein-3 and IL-6, and decreased heparin-binding epidermal growth factor-like growth factor and cyclic guanosine monophosphate. Of all markers studied anti-proliferative factor had the least overlap in the interstitial cystitis and control groups, and so it is the most likely candidate to become a diagnostic test.
Psycho-social aspects of chronic pain in spinal cord injury (1980)

The relationship between persistent pain in spinal cord injury and medical-descriptive, demographic, psychological and familial-social data was studied. Multiple linear regression and discriminant analysis were used to predict (1) presence or absence of pain; (2) severity of pain; (3) time post-injury onset of pain; (4) whether or not pain interfered with activities of daily living. The best combinations of predictor variables accounted for only 15 and 19% of the dependent measures pain vs. no-pain and onset of pain, respectively. The best combinations of predictor variables accounted for 43 and 44%, respectively of the dependent measures severity of pain and whether or not pain interfered with activities of daily living. Higher levels of subjective pain were associated with greater age, higher verbal intelligence, higher levels of anxiety and a more negative psycho-social situation. Persons who reported pain interfering with activities of daily living were more likely to be older, of higher intelligence, more depressed, clinically rated as experiencing greater levels of distress and immersed in a more negative psycho-social environment. The importance of psycho-social variables in the understanding of persistent spinal cord injury pain and the need for prospective studies along these lines are demonstrated.
Design of Selective Neuronal Nitric Oxide Synthase Inhibitors for the Prevention and Treatment of Neurodegenerative Diseases (2009)

Nitric oxide (NO), which is produced from L-arginine by the nitric oxide synthase (NOS) family of enzymes, is an important second-messenger molecule that regulates several physiological functions. In endothelial cells, it relaxes smooth muscle, which decreases blood pressure. Macrophage cells produce NO as an immune defense system to destroy pathogens and microorganisms. In neuronal cells, NO controls the release of neurotransmitters and is involved in synaptogenesis, synaptic plasticity, memory function, and neuroendocrine secretion. NO is a free radical that is commonly thought to contribute to oxidative damage and molecule and tissue destruction, and thus it is somewhat surprising that it has so many significant beneficial physiological effects. However, the cell is generally protected from NO's toxic effects, except under certain pathological conditions in which excessive NO is produced. In that case, tissue damage and oxidative stress can result, leading to a wide variety of diseases, including rheumatoid arthritis, Alzheimer's disease, and Parkinson's disease, among others. In this Account, we describe research aimed at identifying small molecules that can selectively inhibit only the neuronal isozyme of NOS, nNOS. By targeting only nNOS, we attained the beneficial effects of lowering excess NO in the brain without the detrimental effects of inhibition of the two isozymes found elsewhere in the body (eNOS and iNOS). Initially, in pursuit of this goal, we sought to identify differences in the second sphere of amino acids in the active site of the isozymes. From this study, the first class of dual nNOS-selective inhibitors was identified. The moieties important for selectivity in the best lead compound were determined by structure modification. Enhancement provided highly potent, nNOS-selective dipeptide amides and peptidomimetics, which were active in a rabbit model for fetal neurodegeneration. Crystal structures of these compounds bound to NOS isozymes showed a one-amino-acid difference between nNOS and eNOS in the second sphere of amino acids; this was the difference that we were searching for from the beginning of this project. With the aid of these crystal structures, we developed a new fragment-based de novo design method called "fragment hopping", which allowed the design of a new class of nonpeptide nNOS-selective inhibitors. These compounds were modified to give low nanomolar, highly dual-selective nNOS inhibitors, which we recently showed are active in a rabbit model for the prevention of neurobehavioral symptoms of cerebral palsy. These compounds could also have general application in other neurodegenerative diseases for which excess NO is responsible.
Statins: maid-of-all-work in cardiovascular diseases! (2003)

Inhibitors of HMG-CoA reductase (statins) lower the level of circulating LDL-C by blocking the activity of HMG-CoA reductase. Their efficiency to prevent cardiovascular events was demonstrated in several clinical trials for primary and secondary prevention. However, subgroups analysis of trials together with experimental studies have increasingly documented that the beneficial effects of statins extend beyond the sole reduction in LDL-C. These effects include improvements of vasoreactivity, haemostasis and plaque stability, reduction of pro-inflammatory events such as a decrease in monocyte adhesion and infiltration, oxidation level and pericellular proteolysis. Possible repair of ischemic tissues through enhancement of mobilization of endothelial progenitor cells are also described, although more investigation are needed to clearly identify the role and safety of statins in angiogenesis. These pleiotropic effects are generally explained by the fact that statins inhibit the intracellular production of metabolites located downstream of mevalonate in the cholesterol pathway, such as isoprenoids (farnesyl pyrophosphate and geranylgeranylpyrophosphate). These hydrophobic metabolites allow the membrane anchorage of small G proteins (Ras and Rho) as well as the Gy subunit of heterotrimeric G proteins, a post-translational step that is critical in the regulation of G protein signaling activity. These drugs are therefore a valuable tool not only for the clinician but also for the biologist, allowing to investigate the regulation of gene expression that is controlled by the intracellular activity of membrane-anchored prenylated signaling proteins.
Copper-catalyzed reaction of aryl iodides with active methylene compounds (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCopper-catalyzed reaction of aryl iodides with active methylene compoundsKazumi Okuro, Makoto Furuune, Masahiro Miura, and Masakatsu NomuraCite this: J. Org. Chem. 1993, 58, 26, 7606–7607Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/jo00078a053https://doi.org/10.1021/jo00078a053research-articleACS PublicationsRequest reuse permissionsArticle Views3323Altmetric-Citations124LEARN 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
Signal Transducers and Activators of Transcription-3/Pim1 Axis Plays a Critical Role in the Pathogenesis of Human Pulmonary Arterial Hypertension (2011)

We demonstrated for the first time that inhibition of the inappropriate activation of STAT3/Pim1 axis is a novel, specific, and attractive therapeutic strategy to reverse PAH.
Expanding the Ig Superfamily Code for Laminar Specificity in Retina: Expression and Role of Contactins (2012)

Bipolar, amacrine, and retinal ganglion cells elaborate arbors and form synapses within the inner plexiform layer (IPL) of the vertebrate retina. Specific subsets of these neuronal types synapse in one or a few of the ≥10 sublaminae of the IPL. Four closely related Ig superfamily transmembrane adhesion molecules--Sidekick1 (Sdk1), Sdk2, Dscam, and DscamL--are expressed by non-overlapping subsets of chick retinal neurons and promote their lamina-specific arborization (Yamagata and Sanes, 2008). Here, we asked whether contactins (Cntns), six homologs of Sdks and Dscams, are expressed by and play roles in other subsets. In situ hybridization showed that cntn1-5 were differentially expressed by subsets of amacrine cells. Immunohistochemistry showed that each Cntn protein was concentrated in a subset of IPL sublaminae. To assess roles of Cntns in retinal development, we focused on Cntn2. Depletion of Cntn2 by RNA interference markedly reduced the ability of Cntn2-positive cells to restrict their arbors to appropriate sublaminae. Conversely, ectopic expression of cntn2 redirected neurites of transduced neurons to the Cntn2-positive sublaminae. Thus, both loss- and gain-of-function strategies implicate Cntn2 in lamina-specific neurite targeting. Studies in heterologous cells showed that Cntn2 mediates homophilic adhesion, but does not bind detectably to Sdks, Dscams, or other Cntns. Overexpression analysis showed that Cntns1 and 3 can also redirect neurites to appropriate sublaminae. We propose that Cntns, Sdks, and Dscams comprise an Ig superfamily code that uses homophilic interactions to promote lamina-specific targeting of retinal dendrites in IPL.
Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy (2015)

Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.
CRTH2, an orphan receptor of T‐helper‐2‐cells, is expressed on basophils and eosinophils and responds to mast cell‐derived factor(s) (1999)

We have recently cloned a putative chemoattractant receptor, named CRTH2, which is preferentially expressed on human T-helper- (Th) 2 but not Th1 cells. In this study, we demonstrated that CRTH2 is also highly expressed on peripheral blood basophils and eosinophils. Our search for a CRTH2 ligand identified mast cells as the possible producers of a ligand. When stimulated with an anti-FcepsilonR1 antibody, cord blood-derived mast cells secreted factor(s) that induced Ca(2+) mobilization in CRTH2-expressing K562 cells but not in mock transfected cells. These findings implied the involvement of CRTH2 in mast cell-mediated immune responses such as allergic reactions.
Meshless deformations based on shape matching (2005)

We present a new approach for simulating deformable objects. The underlying model is geometrically motivated. It handles pointbased objects and does not need connectivity information. The approach does not require any pre-processing, is simple to compute, and provides unconditionally stable dynamic simulations.The main idea of our deformable model is to replace energies by geometric constraints and forces by distances of current positions to goal positions. These goal positions are determined via a generalized shape matching of an undeformed rest state with the current deformed state of the point cloud. Since points are always drawn towards well-defined locations, the overshooting problem of explicit integration schemes is eliminated. The versatility of the approach in terms of object representations that can be handled, the efficiency in terms of memory and computational complexity, and the unconditional stability of the dynamic simulation make the approach particularly interesting for games.
Control of Cell Growth. IV. Growth Properties of a New Cell Line Established from an Estrogen-Dependent Kidney Tumor of the Syrian Hamster1,2 (1976)

A permanent cell line has been established in culture from an estrogen-dependent kidney tumor of the Syrian hamster. The cells were selected from mixed populations by three methods: 1) animal passage enrichment, 2) growth on petri dishes, and 3) serum-type dependence. The inoculation of these cells, designated the H-301 line, into host animals showed tumor formation in estrogen-treated males or estrogen-treated females, but no tumor formation in normal or castrated hamsters of either sex. The estrogen-dependent tumor formation in male hamsters by H-301 cells was inhibited by progesterone, hydrocortisone, and testosterone. When H-301 cell growth was examined in culture, the addition of estrogens or other steroid hormones to the medium over the range of 0.1 to 10 ng/ml showed no growth-stimulating or inhibiting effects. Medium prepared with charcoal-extracted serum (to reduce by 90% the endogenous levels of steroid hormones) supported growth as well as medium prepared with normal serum. Furthermore, the addition of either estrogens, testosterone, or antiestrogens to medium prepared with charcoal-extracted serum showed no significant effects upon growth. We have shown also that culture medium prepared with serum from young calves did not support the growth of the cells, and the addition of estrogens to this medium did not change this growth pattern. However, the addition of fetal calf serum to medium already containing calf serum promoted maximal growth. Evidence is presented that the growth-promoting agent in fetal calf serum was inactivated by a 90 C heat treatment. Furthermore, the ether-soluble fractions from fetal calf serum and horse serum did not significantly improve growth when added to calf serum containing medium. We conclude that estrogens or other steroid hormones alone are not sufficient to promote the growth of the H-301 cells, but that heat-labile serum factors are required.
Determination of Immunity to Varicella-Zoster Virus by Means of an Intradermal Skin Test (1985)

Journal Article Determination of Immunity to Varicella-Zoster Virus by Means of an Intradermal Skin Test Get access Philip LaRussa, Philip LaRussa From the Department of Pediatrics, New York University Medical Center, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Sharon Projansky Steinberg, Sharon Projansky Steinberg From the Department of Pediatrics, New York University Medical Center, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Melinda D. Seeman, Melinda D. Seeman From the Department of Pediatrics, New York University Medical Center, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Anne A. Gershon Anne A. Gershon From the Department of Pediatrics, New York University Medical Center, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 152, Issue 5, November 1985, Pages 869–875, https://doi.org/10.1093/infdis/152.5.869 Published: 01 November 1985 Article history Received: 21 January 1985 Revision received: 01 May 1985 Published: 01 November 1985
In Vivo Measurement of Swine Endocardial Convective Heat Transfer Coefficient (2004)

We measured the endocardial convective heat transfer coefficient h at 22 locations in the cardiac chambers of 15 pigs in vivo. A thin-film Pt catheter tip sensor in a Wheatstone-bridge circuit, similar to a hot wire/film anemometer, measured h. Using fluoroscopy, we could precisely locate the steerable catheter sensor tip and sensor orientation in pigs' cardiac chambers. With flows, h varies from 2500 to 9500 W/m2 x K. With zero flow, h is approximately 2400 W/m2 x K. These values of h can be used for the finite element method modeling of radiofrequency cardiac catheter ablation.
Bioactive Macrocyclic Inhibitors of the PD‐1/PD‐L1 Immune Checkpoint (2017)

Blockade of the immunoinhibitory PD-1/PD-L1 pathway using monoclonal antibodies has shown impressive results with durable clinical antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have now been approved for the treatment of a number of tumor types, whereas the development of small molecules targeting immune checkpoints lags far behind. We characterized two classes of macrocyclic-peptide inhibitors directed at the PD-1/PD-L1 pathway. We show that these macrocyclic compounds act by directly binding to PD-L1 and that they are capable of antagonizing PD-L1 signaling and, similarly to antibodies, can restore the function of T-cells. We also provide the crystal structures of two of these small-molecule inhibitors bound to PD-L1. The structures provide a rationale for the checkpoint inhibition by these small molecules, and a description of their small molecule/PD-L1 interfaces provides a blueprint for the design of small-molecule inhibitors of the PD-1/PD-L1 pathway.
Sequence comparison and secondary structure analysis of the 3' noncoding region of flavivirus genomes reveals multiple pseudoknots. (2001)

Sequences of 191 flavivirus RNAs belonging to four sero-groups were used to predict the secondary structure of the 3' noncoding region (3' NCR) directly upstream of the conserved terminal hairpin. In mosquito-borne flavivirus RNAs (n = 164) a characteristic structure element was identified that includes a phylogenetically well-supported pseudoknot. This element is repeated in the dengue and Japanese encephalitis RNAs and centers around the conserved sequences CS2 and RCS2. In yellow fever virus RNAs that contain one CS2 motif, only one copy of this pseudoknotted structure was found. The conserved pseudoknotted element is absent from the 3' NCR of tick-borne virus RNAs, which altogether adopt a secondary structure that is very different from that of mosquito-borne virus RNAs. The strong conservation of the pseudoknot in mosquito-borne flavivirus RNAs implies a stronger relationship between these viruses than concluded from previous secondary structure analyses. The role of the (tandem) pseudoknots in flavivirus replication is discussed.