gebhart/patrepeval huggingface dataset:
The Herpes Simplex Virus JMP Mutant Enters Receptor-Negative J Cells through a Novel Pathway Independent of the Known Receptors nectin1, HveA, and nectin2 (2004)

The herpes simplex virus type 1(JMP) [HSV-1(JMP)] mutant was selected for its ability to grow and form plaques in receptor-negative J cells. It enters J cells through a novel gD-dependent pathway, independent of all known HSV receptors, nectin1, nectin2, and HveA. Evidence that the pathway is dependent on a nectin3 binding site on HSV-1(JMP) and requires three mutations in gD rests on the following. We derived monoclonal antibodies to nectin3 and show that J cells express nectin3. HSV-1(JMP) entry and cell-to-cell spread were inhibited by soluble nectin3-Fc, demonstrating that virions carry a binding site for nectin3. The site is either directly involved in HSV-1(JMP) entry, or nectin3 binding to its site affects the gD domains involved in entry (entry site). HSV-1(JMP) entry and cell-to-cell spread in J cells were also inhibited by soluble nectin1-Fc, showing that the nectin1 binding site on gD(JMP) overlaps with the entry site or that nectin1 binding to gD affects the entry site. gD(JMP) carries three mutations, S140N, R340H, and Q344R. The latter two lie in the C tail and are present in the parental HSV-1(MP). HSV-1 strain R5000 carrying the S140N substitution was not infectious in J cells, indicating that this substitution was not sufficient. We constructed two recombinants, one carrying the three substitutions and the other carrying the two C-tail substitutions. Only the first recombinant infected J cells with an efficiency similar to that of HSV-1(JMP), indicating that the three mutations are required for the novel entry pathway. The results highlight plasticity in gD which accounts for changes in receptor usage.
Cooperative NCoR/SMRT interactions establish a corepressor-based strategy for integration of inflammatory and anti-inflammatory signaling pathways (2009)

Innate immune responses to bacterial or viral infection require rapid transition of large cohorts of inflammatory response genes from poised/repressed to actively transcribed states, but the underlying repression/derepression mechanisms remain poorly understood. Here, we report that, while the nuclear receptor corepressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) corepressors establish repression checkpoints on broad sets of inflammatory response genes in macrophages and are required for nearly all of the transrepression activities of liver X receptors (LXRs), they can be selectively recruited via c-Jun or the Ets repressor Tel, respectively, establishing NCoR-specific, SMRT-specific, and NCoR/SMRT-dependent promoters. Unexpectedly, the binding of NCoR and SMRT to NCoR/SMRT-dependent promoters is frequently mutually dependent, establishing a requirement for both proteins for LXR transrepression and enabling inflammatory signaling pathways that selectively target NCoR or SMRT to also derepress/activate NCoR/SMRT-dependent genes. These findings reveal a combinatorial, corepressor-based strategy for integration of inflammatory and anti-inflammatory signals that play essential roles in immunity and homeostasis.
Comparing outcomes of different treatment regimens for severe haemophilia (2003)

Published retrospective reports from France, the Netherlands and Sweden were analysed for data relating to the long-term outcomes (primarily the development of arthropathy) of three regimens for the management of severe haemophilia: on-demand treatment, intermediate-dose prophylaxis and high-dose prophylaxis. The mean annual consumption of factor concentrate was also compared. These data indicate that both prophylaxis regimens resulted in significantly improved long-term outcomes, as assessed by pain, clinical and radiological assessment scores. At the same time, the most recently reported annual factor consumption levels of these young adult patients are comparable in the on-demand and intermediate-dose prophylaxis cohorts, suggesting that the improvement in long-term clinical outcomes and reduced risk of arthropathy may lead to reduced factor consumption in adult patients who received early prophylactic therapy.
A Three-Component Tandem Reductive Aldol Reaction Catalyzed by N-Heterocyclic Carbene−Copper Complexes (2006)

[Structure: see text] An efficient catalytic system for the three-component coupling of electrophilic alkenes, aldehydes, and silane was optimized with a new family of copper N-heterocyclic carbene complexes. These catalysts do not require activation and show high activity (TOF>15,000 h-1) as well as some anti diastereoselectivity.
Identification of Allergens in Dermatophagoides pteronyssinus Mite Body Extract by Crossed Radioimmunoelectrophoresis with Two Different Rabbit Antibody Pools (1983)

An extract of purified Dermatophagoides pteronyssinus mite bodies was investigated by crossed radioimmunoelectrophoresis (CRIE), using sera from 29 mite-allergic patients. Two CRIE series consisting of rabbit antibodies to (1) whole mite culture and to (2) purified mite bodies were run simultaneously, showing 27 and 29 precipitates, respectively. Cases of major discrepancy between the two series were ascribed to absence of antibody to allergenic components and to artefactual radiostaining due to inclusion of allergen in precipitates representing other antigens. Carefully performed controls were necessary to establish the reliability of CRIE. Specific response patterns in the studied set of sera were found to several of the represented antigens. Two major allergens appeared in both CRIE systems. Two intermediate and several minor allergens were further identified.
Cell-surface marker discovery for lung cancer (2017)

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan-Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.
Control of Cell Divisions in the Nervous System: Symmetry and Asymmetry (2000)

The diverse cell types in the nervous system are derived from neural progenitor cells. Neural progenitors can undergo symmetric divisions to expand cell population or asymmetric divisions to generate diverse cell types. Furthermore, neural progenitors must exit the cell cycle in a developmentally regulated manner to allow for terminal differentiation. The patterns of neural progenitor divisions have been characterized in vertebrates and invertebrates. During the course of nervous system development, extrinsic and intrinsic cues dictate the division patterns of neural progenitors by influencing their cell cycle behavior and cellular polarity. The identification in Drosophila of asymmetrically distributed fate determinants, adapter molecules, and polarity organizing molecules that participate in asymmetric neural progenitor divisions should provide points of entry for studying similar asymmetric divisions in vertebrates.
Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine in Genomic DNA from Hepatocellular Carcinoma Tissues by Capillary Hydrophilic-Interaction Liquid Chromatography/Quadrupole TOF Mass Spectrometry (2013)

The marked depletion of 5-hmC may have profound effects on epigenetic regulation in HCC and could be a potential biomarker for the early detection and prognosis of HCC.
Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. (1994)

We have found several genetic changes in the TGF-beta-type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA.
Detection of Surface Antigen 17-1A in Breast and Colorectal Cancer (1999)

Substantial progress has been made in detecting cell surface or intracytoplasmatic antigens to identify spread tumor cells with monoclonal antibodies (MAbs). The 17-1A antigen is already used as a target for specific immunotherapy in colorectal cancer. The purpose of this study was to compare the expression of 17-1A antigen in colorectal tumors versus breast cancers. MAb against the epithelial-specific antigen (ESA) and a routine staining technique were used to detect the 17-1A antigen in 100 cases of colorectal and 111 cases of breast cancer. The antigen expression of each tumor entity was examined by light microscopy on paraffin sections. Thirty six of the formalin-fixed paraffin sections of breast cancer were compared with their corresponding frozen sections. Evaluation was realized by a histological score (grade 0-9) considering the distribution and the staining intensity. We found an antigen expression of 17-1A in colorectal cancer quantified at 7.1+/-1.8 and at 4.5+/-2.5 for breast cancer in our score. Comparing paraffin sections and frozen sections in the 36 cases of breast cancer, the score was 5.5+/-2.3 in the paraffin and 8.1+/-1.9 in the frozen section group. Our results confirmed the high expression of 17-1A cases of in colorectal carcinoma. Furthermore, 17-1A is expressed in the majority of breast carcinomas, revealing a high difference between paraffin and frozen sections. As a result, a specific immunotherapy with MAbs against 17-1A antigen in minimal residual stages of breast cancer might be considered.
Effect of alteration of the acetic acid synthesis pathway on the fermentation pattern of escherichia coli (1991)

The glucose metabolism of an Escherichia coli strain bearing mutations abolishing both acetyl phosphotransferase (PTA) and acetate kinase (ACK) activities was studied under aerobic and anaerobic conditions. These studies were conducted in a complex medium with the mutant carrying no plasmid, the mutant carrying the common cloning vector pUC19, and the mutant carrying a plasmid bearing the "pet" operon that encodes Zymomonas mobilis pyruvate decarboxylase and alcohol dehydrogenase activities. The mutant carrying no plasmid showed lower specific growth and glucose uptake rates relative to the parent wild-type strain (K-12), Lactic acid was produced at higher levels than the wild type, and considerable amounts of pyruvic acid were secreted as an unusual byproduct. Analysis of other fermentation products showed low but significant amounts of acetic acid, no accumulation of formic acid, and lower secretion of succinate and ethanol. The maintenance of the plasmid pUC19 in the mutant negatively affected metabolism. Expression of the pet operon overcame the metabolic stress caused by the plasmid, enhancing growth and glucose uptake rates to the values observed in the plasmidfree mutant. Also, expression of the pet operon allowed consumption of pyruvate accumulated during the first hours of fermentation.
Effects of low-energy gallium-aluminum-arsenide laser irradiation on cultured fibroblasts and keratinocytes (1997)

The gallium-aluminum-arsenide laser, when utilized at powers 5-100 milliwatts and times of between 10-120 seconds has no biostimulatory effects on fibroblasts or keratinocyte cultures as assessed by cell proliferation, adhesion, or migration.
Phospholipids coupled to a carrier induce IgG antibody that blocks tumour necrosis factor induction by toxic malaria antigens. (1993)

Phospholipid-containing antigens of malaria parasites stimulate macrophages to secrete tumour necrosis factor (TNF), induce hypoglycaemia and are toxic to mice. This TNF induction is inhibited by antisera made against the antigens, the inhibitory activity of which can be removed specifically by adsorption to phosphatidylinositol (PI) liposomes. Although the same was true of antisera made against PI, the inhibitory activity of antisera made against some other phospholipids appeared to be directed against a common determinant, probably the phosphate ester head group. We have shown previously that the activity of all the antisera was associated mainly with IgM and was not boosted by repeated injections of the antigens. To try and induce a secondary response against the parasite antigens using non-toxic molecules, mice were immunized with various phosphorylated compounds coupled to keyhole limpet haemocyanin (KLH). Three injections of PI-KLH or of phosphatidylserine (PS) coupled to KLH induced significantly higher titres of inhibitory antibody than one; furthermore, the inhibitory activity was mainly in the IgG fraction. The antisera did not inhibit TNF induction by lipopolysaccharide (LPS) or lipoteichoic acid. However, antisera against PS-KLH, though not PI-KLH, inhibited the induction of TNF by the phospholipid, platelet-activating factor (PAF). These antisera, and antisera from mice immunized with phospho-threonine or galactosamine-1-phosphate conjugated to KLH, contained inhibitory antibodies of differing specificities. Mice immunized with PI-KLH, PS-KLH or phospho-threonine-KLH did not develop hypoglycaemia when challenged with the parasite toxic antigens. These results indicate that the antigenicity of non-toxic analogues can be dramatically enhanced by coupling to a protein carrier.
Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction (2000)

Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.
Resveratrol Induces Long-Lasting IL-8 Expression and Peculiar EGFR Activation/Distribution in Human Keratinocytes: Mechanisms and Implications for Skin Administration (2013)

Resveratrol synergized with TNFα in the induction of delayed, long-lasting IL-8 expression through sustained EGFR-ERK axis activation. The time course indicates that resveratrol metabolites could be implicated. Topical administration of Resv to psoriatic patients over-expressing TNFα, IL-8 and EGFR-ERK in the skin should be cautiously considered. Since high nuclear levels of EGFR correspond to increased risk of tumorigenesis, chronic resveratrol application to the skin may be potentially dangerous. Wound healing acceleration by resveratrol could not be envisaged due to its anti-proliferative effects towards normal keratinocytes.
Neuropeptides in hypertension: role of neuropeptide Y and calcitonin gene related peptide. (1990)

1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague-Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfused mesenteric arterial bed, NPY and the structurally similar peptide intestinal polypeptide (PYY) decreased the periarterial nerve stimulation induced release of NA and potentiated the increase in perfusion pressure to nerve stimulation or exogenously applied agonists (e.g. angiotensin, vasopressin, phenylephrine). In contrast to NPY and PYY, C-terminal NPY fragments inhibited NA release and produced a parallel decrease in perfusion pressure thus supporting the concept of Y1 (post) and Y2 (pre) NPY receptors. 3. In the mesenteric artery of SHR the prejunctional inhibitory effect of NPY was attenuated while the postjunctional response was enhanced. 4. Following intrathecal (Int) injection of NPY, there was a decrease in blood pressure, total peripheral resistance (predominantly by a decrease in mesenteric vascular resistance) and renal nerve activity. The depressor effect of Int NPY was attenuated in the SHR. 5. Unilateral injections of NPY into the posterior hypothalamic nucleus increased blood pressure, hindquarter and renal vascular resistance and renal nerve activity. The pressor effect was enhanced in the SHR. 6. Periarterial nerve stimulation of the perfused mesenteric artery produced a frequency dependent vasodilation in beds pretreated with guanethidine and precontracted with methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrochemical characterization of Pt–Ru–Ni/C anode electrocatalyst for methanol electrooxidation in membraneless fuel cells (2015)

In the present work, carbon-supported Pt–Ru, Pt–Ni and Pt–Ru–Ni electrocatalysts with different atomic ratios were synthesized by NaBH<sub>4</sub> reduction method.
High Processivity of the Reverse Transcriptase from a Non-long Terminal Repeat Retrotransposon (2002)

R2 is a retrotransposable element that specifically inserts into the 28 S rRNA genes of arthropods. The element encodes a single protein with endonuclease activity that cleaves the 28 S gene target site and reverse transcriptase (RT) activity that uses the cleaved DNA to prime reverse transcription. Here we compare various properties of the R2 RT activity with those of the well characterized retroviral RT, avian myeloblastosis virus (AMV). In processivity assays using heterogeneous RNA templates, R2 RT can synthesize cDNA over twice the length of that synthesized by AMV RT and can synthesize cDNA over 4 times longer than AMV RT in assays with poly(rA) templates. The higher processivity of R2 RT compared with retroviral RTs is a result of the slower rate of dissociation of the enzyme from RNA templates. The elongation rates of the two enzymes are similar. Finally, a highly distinct property of the R2 RT, compared with retroviral enzymes, is its ability to displace RNA strands annealed to RNA templates during cDNA synthesis. We suggest that both the higher processivity and displacement properties of R2 RT compared with retroviral RT result from the greater affinity of the R2 protein for the RNA template upstream of its active site.
Trends in Long-Term Survival Following Liver Resection for Hepatic Colorectal Metastases (2002)

Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.
Human Dendritic Cells Mediate Cellular Apoptosis via Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) (1999)

TRAIL (TNF-related apoptosis-inducing ligand) is a member of the TNF family that induces apoptosis in a variety of cancer cells. In this study, we demonstrate that human CD11c(+) blood dendritic cells (DCs) express TRAIL after stimulation with either interferon (IFN)-gamma or -alpha and acquire the ability to kill TRAIL-sensitive tumor cell targets but not TRAIL-resistant tumor cells or normal cell types. The DC-mediated apoptosis was TRAIL specific, as soluble TRAIL receptor blocked target cell death. Moreover, IFN-stimulated interleukin (IL)-3 receptor (R)alpha(+) blood precursor (pre-)DCs displayed minimal cytotoxicity toward the same target cells, demonstrating a clear functional difference between the CD11c(+) DC and IL-3Ralpha(+) pre-DC subsets. These results indicate that TRAIL may serve as an innate effector molecule on CD11c(+) DCs for the elimination of spontaneously arising tumor cells and suggest a means by which TRAIL-expressing DCs may regulate or eliminate T cells responding to antigen presented by the DCs.
Structure and developmental regulation of the B-lymphoid tyrosine kinase gene blk. (1992)

The murine blk gene, which encodes a B-lymphoid-specific tyrosine kinase of the Src family (p55blk), contains 13 exons that span more than 30 kilobases of DNA on chromosome 14. In the first three exons, which encode the 5'-untranslated region and N-terminal amino acid sequence unique to p55blk, the blk gene differs from other members of the src family; in the last 10 exons, the organization of the blk gene is similar to that of other src genes. By primer extension and S1 nuclease protection analyses, we show that blk transcripts initiate from four major sites at the 5'-flank of blk; two sites predominate. The resulting transcripts differ only in the lengths of their 5'-untranslated sequences and encode identical proteins. None of the transcriptional start sites are preceded by consensus TATA elements, AT-rich elements, or extensive GC-rich regions. Expression of blk is regulated during B-cell development: blk RNA is expressed in all pro-B-, pre-B-, and mature B-cell lines examined, but is absent from plasma cell lines. Immunolocalization of p55blk in normal mouse spleen supports these observations: staining is restricted to lymphocytes and is concentrated in regions rich in B-cells; plasma cells and stromal cells are not stained with anti-Blk antibodies. Assays for RNA synthesis in isolated nuclei indicate that the lineage and developmental stage specificities of blk expression are regulated at least in part by changes in its rate of transcription.