gebhart/patrepeval huggingface dataset:
Probing Spindle Assembly Mechanisms with Monastrol, a Small Molecule Inhibitor of the Mitotic Kinesin, Eg5 (2000)

Monastrol, a cell-permeable small molecule inhibitor of the mitotic kinesin, Eg5, arrests cells in mitosis with monoastral spindles. Here, we use monastrol to probe mitotic mechanisms. We find that monastrol does not inhibit progression through S and G2 phases of the cell cycle or centrosome duplication. The mitotic arrest due to monastrol is also rapidly reversible. Chromosomes in monastrol-treated cells frequently have both sister kinetochores attached to microtubules extending to the center of the monoaster (syntelic orientation). Mitotic arrest-deficient protein 2 (Mad2) localizes to a subset of kinetochores, suggesting the activation of the spindle assembly checkpoint in these cells. Mad2 localizes to some kinetochores that have attached microtubules in monastrol-treated cells, indicating that kinetochore microtubule attachment alone may not satisfy the spindle assembly checkpoint. Monastrol also inhibits bipolar spindle formation in Xenopus egg extracts. However, it does not prevent the targeting of Eg5 to the monoastral spindles that form. Imaging bipolar spindles disassembling in the presence of monastrol allowed direct observations of outward directed forces in the spindle, orthogonal to the pole-to-pole axis. Monastrol is thus a useful tool to study mitotic processes, detection and correction of chromosome malorientation, and contributions of Eg5 to spindle assembly and maintenance.
Suppression of immune responses by dendritic cells infected with HIV. (1989)

Evidence of human immunodeficiency virus (HIV) replication both in the skin Langerhans' cells of AIDS patients (Tschachler et al., 1987) and in normal, peripheral blood dendritic cells (DC) (Patterson & Knight, 1987; Knight & Patterson, 1989) suggests that infection of these antigen-presenting cells may contribute to the immunosuppression seen in AIDS. Support for this hypothesis is now provided by experiments in which the capacity of DC infected in vitro to present mitogen to normal syngeneic lymphocytes was measured. Infecting DC with HIV before culturing with lymphocytes inhibited mitogen-stimulated cell proliferation. Viral DNA was detected in DC in these cultures by in situ hybridization but, in addition, HIV was also present in a small proportion of lymphocytes. However, introducing an inhibitor of virus replication, 2',3' dideoxyadenosine, after infection of the DC but before culturing with lymphocytes, blocked growth of HIV in lymphocytes. In these latter experiments mitogen proliferation responses were still suppressed. Infection of DC could, therefore, cause immunosuppression in AIDS, both by direct effect on antigen-presentation and by the transfer of HIV to T cells.
CC-1065 partial structures: enhancement of noncovalent affinity for DNA minor groove binding through introduction of stabilizing electrostatic interactions (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCC-1065 partial structures: enhancement of noncovalent affinity for DNA minor groove binding through introduction of stabilizing electrostatic interactionsDale L. Boger and Subas M. SakyaCite this: J. Org. Chem. 1992, 57, 4, 1277–1284Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/jo00030a042https://doi.org/10.1021/jo00030a042research-articleACS PublicationsRequest reuse permissionsArticle Views166Altmetric-Citations26LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Systematic Assembly of a Full-Length Infectious cDNA of Mouse Hepatitis Virus Strain A59 (2002)

A novel method was developed to assemble a full-length infectious cDNA of the group II coronavirus mouse hepatitis virus strain A59 (MHV-A59). Seven contiguous cDNA clones that spanned the 31.5-kb MHV genome were isolated. The ends of the cDNAs were engineered with unique junctions and assembled with only the adjacent cDNA subclones, resulting in an intact MHV-A59 cDNA construct of approximately 31.5 kb in length. The interconnecting restriction site junctions that are located at the ends of each cDNA are systematically removed during the assembly of the complete full-length cDNA product, allowing reassembly without the introduction of nucleotide changes. RNA transcripts derived from the full-length MHV-A59 construct were infectious, although transfection frequencies were enhanced 10- to 15-fold in the presence of transcripts encoding the nucleocapsid protein N. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar growth kinetics, plaque morphology, and cytopathology in murine cells as did wild-type MHV-A59. Molecularly cloned viruses recognized the MHV receptor (MHVR) for docking and entry, and pretreatment of cells with monoclonal antibodies against MHVR blocked virus entry and replication. Cells infected with molecularly cloned MHV-A59 virus expressed replicase (gene 1) proteins identical to those of laboratory MHV-A59. Importantly, the molecularly cloned viruses contained three marker mutations that had been derived from the engineered component clones. Full-length infectious constructs of MHV-A59 will permit genetic modifications of the entire coronavirus genome, particularly in the replicase gene. The method has the potential to be used to construct viral, microbial, or eukaryotic genomes approaching several million base pairs in length and used to insert restriction sites at any given nucleotide in a microbial genome.
Type 1 Diabetes in the BB Rat: A Polygenic Disease (2009)

This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes.
Oral Viscous Budesonide: A Potential New Therapy for Eosinophilic Esophagitis in Children (2007)

Topical viscous budesonide is a safe and effective therapy for EE in young children.
Tailored transgene expression to specific cell types in the central nervous system after peripheral injection with AAV9 (2016)

The capacity of certain adeno-associated virus (AAV) vectors to cross the blood-brain barrier after intravenous delivery offers a unique opportunity for noninvasive brain delivery. However, without a well-tailored system, the use of a peripheral route injection may lead to undesirable transgene expression in nontarget cells or organs. To refine this approach, the present study characterizes the transduction profiles of new self-complementary AAV9 (scAAV9) expressing the green fluorescent protein (GFP) either under an astrocyte (glial fibrillary acidic (GFA) protein) or neuronal (Synapsin (Syn)) promoter, after intravenous injection of adult mice (2 × 10<sup>13</sup> vg/kg). ScAAV9-GFA-GFP and scAAV9-Syn-GFP robustly transduce astrocytes (11%) and neurons (17%), respectively, without aberrant expression leakage. Interestingly, while the percentages of GFP-positive astrocytes with scAAV9-GFA-GFP are similar to the performances observed with scAAV9-CBA-GFP (broadly active promoter), significant higher percentages of neurons express GFP with scAAV9-Syn-GFP. GFP-positive excitatory as well as inhibitory neurons are observed, as well as motor neurons in the spinal cord. Additionally, both activated (GFAP-positive) and resting astrocytes (GFAP-negative) express the reporter gene after scAAV9-GFA-GFP injection. These data thoroughly characterize the gene expression specificity of AAVs fitted with neuronal and astrocyte-selective promoters after intravenous delivery, which will prove useful for central nervous system (CNS) gene therapy approaches in which peripheral expression of transgene is a concern.
Effect of Lidocaine Pretreatment on Endotoxin-induced Lung Injury in Rabbits (1994)

These results suggest that intravenous lidocaine pretreatment has a prophylactic effect on endotoxin-induced lung injury in rabbits. However, further studies are required to investigate the therapeutic (as an early posttreatment) effect of the drug given after lung injury because rabbits in the current study received lidocaine before endotoxemia.
The Italian Regulatory Guidelines for the implementation of Patient Blood Management. (2017)

Comment in Towards the implementation of patient blood management across Europe. [Blood Transfus. 2017]
Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors (2012)

Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of pruritogen-responsive DRG cells, 11.8-26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.
Induction and reversal of long-term potentiation by low- and high- intensity theta pattern stimulation (1995)

Reversal of long-term potentiation by low-frequency stimulation is often referred to as depotentiation. However, it is not clear whether depotentiation induced by low-frequency stimulation and long-term depression (LTD) induced by similar stimuli are distinct phenomena. We have performed a series of experiments in area CA1 of rat hippocampal slices in which a single pattern of theta-burst (TB) stimulation (Larson, et al., 1986; Staubli and Lynch, 1987) was found to produce either LTP or reversal of LTP depending on the intensity of the stimulation. TB stimulation (10 trains consisting of 4 pulses at 100 Hz, 200 msec apart) delivered at test pulse-intensity induced LTP. However, the same stimulation delivered at a higher intensity (10 times that of the test pulse, evoking a maximal response) did not induce LTP or depression of control responses, but produced lasting depression of previously potentiated responses. This reversal of LTP (TB depotentiation) was observed when the stimulus was delivered between 0.5 and 110 min after induction of LTP. TB depotentiation was reversible, cumulative and saturable when high-intensity TB trains were delivered in succession. TB depotentiation was also blocked by antagonists at NMDA receptors. Low-frequency (1 Hz) stimulation induced LTD, indicating that responses were not already maximally depressed. In addition, high-intensity TB stimulation did not reverse LTD. These results suggest that depotentiation induced by maximal TB stimulation and LTD induced by low-frequency stimulation are distinct phenomena, yet share some characteristics common to forms synaptic plasticity mediated by NMDA receptor activation.
PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments (1994)

The present study was undertaken to investigate the presence of C-type natriuretic peptide (CNP) mRNA and its receptor, natriuretic peptide B-type receptor (ANPR-B) mRNA, in rat renal structures. The microlocalization of mRNAs coding for CNP and ANPR-B was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments, glomeruli, vasa recta bundle, and arcuate arteries. The PCR signal for CNP was detected in glomerulus, vasa recta bundle, and arcuate artery. The PCR product of ANPR-B was widely present in renal structures. Relatively large amounts of ANPR-B PCR product were detected in glomerulus, vasa recta bundle, arcuate artery, and distal nephron segments. A relatively high concentration of CNP (10(-7) M) stimulated guanosine 3',5'-cyclic monophosphate accumulation in glomerulus, medullary thick ascending limb, cortical collecting duct, and inner medullary collecting duct. Our data demonstrate that CNP can be produced locally in the glomerulus and renal vascular system and that ANPR-B is widely distributed in renal structures. Thus CNP may influence renal function and act in autocrine and paracrine fashions in the kidney.
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice (2010)

As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.
α1-Antitrypsin monotherapy prolongs islet allograft survival in mice (2005)

Islet transplantation for type 1 diabetic patients shows promising results with the use of nondiabetogenic immunosuppressive therapy. However, in addition to compromising the immune system of transplant recipients, long-term studies demonstrate that islet viability is impaired. Here, we demonstrate that, in the absence of immunosuppressive agents, monotherapy with clinical-grade human alpha1-antitrypsin (hAAT), the major serum serine-protease inhibitor, prolongs islet graft survival and normoglycemia in transplanted allogeneic diabetic mice, lasting until the development of anti-hAAT antibodies. Compared to untreated or albumin-control-treated graft recipients, which rejected islets at day 10, AAT-treated mice displayed diminished cellular infiltrates and intact intragraft insulin production throughout treatment. Using peritoneal infiltration models, we demonstrate that AAT decreases allogeneic fibroblast-elicited natural-killer-cell influx by 89%, CD3-positive cell influx by 44%, and thioglycolate-elicited neutrophil emigration by 66%. ATT also extended islet viability in mice after streptozotocin-induced beta cell toxicity. In vitro, several islet responses to IL-1beta/IFNgamma stimulation were examined. In the presence of AAT, islets displayed enhanced viability and inducible insulin secretion. Islets also released 36% less nitric oxide and 82% less macrophage inflammatory protein 1 alpha and expressed 63% fewer surface MHC class II molecules. TNFalpha release from IL-1beta/IFNgamma-stimulated islet cells was reduced by 99%, accompanied by an 8-fold increase in the accumulation of membrane TNFalpha on CD45-positive islet cells. In light of the established safety record and the nondiabetogenic potential of AAT, these data suggest that AAT may be beneficial as adjunctive therapy in patients undergoing islet transplantation.
Chemotherapy of murine ovarian carcinoma by methotrexate-antibody conjugates (1977)

Antibodies with specificity for an experimental ovarian carcinoma were coupled to methotrexate by two procedures. Water-soluble carbodiimide gave effective coupling, but a large proportion of the conjugate was rendered insoluble, presumably due to alteration or aggregation of the antibodies. A modification of the mixed anhydride procedure gave rise to products which were completely soluble and allowed a high degree of coupling to be achieved. In vivo testing of the conjugates revealed a significant increase in survival time in treated mice when compared to a variety of control groups; these included groups receiving antiserum or drug alone, mixtures of the two, and conjugates of normal gamma-globulin with methotrexate. Our results provide added support for the concept that tumor-associated antibodies coupled to cytotoxic agents are more effective than single agents or noncoupled mixtures of agents.
Highly P-Typed Mg-Doped GaN Films Grown with GaN Buffer Layers (1991)

Mg-doped GaN films were grown with GaN buffer layers on a sapphire substrate. Hall-effect measurement of as-grown GaN films showed that the hole concentration was 2×10 15 /cm 3 , the hole mobility was 9 cm 2 /V·s and the resistivity was 320 Ω·cm at room temperature. After the low-energy electron-beam irradiation (LEEBI) treatment, each value became 3×10 18 /cm 3 , 9 cm 2 /V·s and 0.2 Ω·cm at room temperature, respectively. This value of the hole concentration is the highest ever reported for the p-type GaN films and that of the resistivity is the lowest.
Composition of human zona pellucida as revealed by SDS‐PAGE after silver staining (1995)

The macromolecular composition of zona pellucida (ZP) isolated from human oocytes and embryos was characterized by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1-D- and 2-D-SDS-PAGE) under reducing conditions after silver staining. ZP specimens obtained after in vitro fertilization were removed from pools of heavily fragmented embryos and inseminated oocytes that failed to fertilize. For unfertilized oocytes, two major bands with an apparent molecular weight of, respectively, 96 and 76-54 kDa were observed after 1-D-SDS-PAGE and silver staining. When ZP were isolated from fragmented embryos, the electrophoretic pattern showed a marked attenuation of the 96-kDa band. Silver-stained 2-D-SDS-PAGE analysis of ZP components from unfertilized oocytes revealed the presence of four protein trains: ZP1 (Mr = 92-80 kDa, pl = 4.9-5.9), ZP2 (Mr = 66-58 kDa, pl = 5.0-6.0), ZP3H (high) (Mr = 72-58 kDa, pl = 3.5-5.1), and ZP3L (low) (Mr = 62-54 kDa, pl = 3.5-5.1). The human ZP3 family (ZP3H and ZP3L) showed marked heterogeneity. Fertilization-associated changes were apparent in the electrophoretic pattern. ZP1 (Mr = 92-86 kDa, pl = 5.0-5.8) displayed a dramatic decrease in intensity, and a new component had migrated to a position similar to that of ZP2. This modification may have been responsible for one aspect of the zona reaction, and could have contributed to a zona block to polysperma.
Pyrimidines. IV. Aziridinylpyrimidines1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPyrimidines. IV. Aziridinylpyrimidines1HENRY C. KOPPEL, ROBERT HENRE SPRINGER, and C. C. CHENGCite this: J. Org. Chem. 1961, 26, 6, 1884–1890Publication Date (Print):June 1, 1961Publication History Published online1 May 2002Published inissue 1 June 1961https://pubs.acs.org/doi/10.1021/jo01065a047https://doi.org/10.1021/jo01065a047research-articleACS PublicationsRequest reuse permissionsArticle Views183Altmetric-Citations10LEARN 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
Targeting XIAP Bypasses Bcl-2–Mediated Resistance to TRAIL and Cooperates with TRAIL to Suppress Pancreatic Cancer Growth In vitro and In vivo (2008)

Resistance to apoptosis is a hallmark of pancreatic cancer, a leading cause of cancer deaths. Therefore, novel strategies are required to target apoptosis resistance. Here, we report that the combination of X-linked inhibitor of apoptosis (XIAP) inhibition and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective approach to trigger apoptosis despite Bcl-2 overexpression and to suppress pancreatic cancer growth in vitro and in vivo. Knockdown of XIAP by RNA interference cooperates with TRAIL to induce caspase activation, loss of mitochondrial membrane potential, cytochrome c release, and apoptosis in pancreatic carcinoma cells. Loss of mitochondrial membrane potential and cytochrome c release are extensively inhibited by a broad range or caspase-3 selective caspase inhibitor and by RNAi-mediated silencing of caspase-3, indicating that XIAP inhibition enhances TRAIL-induced mitochondrial damage in a caspase-3-dependent manner. XIAP inhibition combined with TRAIL even breaks Bcl-2-imposed resistance by converting type II cells that depend on the mitochondrial contribution to the death receptor pathway to type I cells in which TRAIL-induced activation of caspase-3 and caspase-9 and apoptosis proceeds irrespective of high Bcl-2 levels. Most importantly, XIAP inhibition potentiates TRAIL-induced antitumor activity in two preclinical models of pancreatic cancer in vivo. In the chicken chorioallantoic membrane model, XIAP inhibition significantly enhances TRAIL-mediated apoptosis and suppression of tumor growth. In a tumor regression model in xenograft-bearing mice, XIAP inhibition acts in concert with TRAIL to cause even regression of established pancreatic carcinoma. Thus, this combination of XIAP inhibition plus TRAIL is a promising strategy to overcome apoptosis resistance of pancreatic cancer that warrants further investigation.