gebhart/patrepeval huggingface dataset:
Biodehalogenation. Pathway for transhalogenation and the stereochemistry of eposide formation from halohydrins (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiodehalogenation. Pathway for transhalogenation and the stereochemistry of eposide formation from halohydrinsE. W. Bartnicki and C. E. CastroCite this: Biochemistry 1969, 8, 12, 4677–4680Publication Date (Print):December 1, 1969Publication History Published online1 May 2002Published inissue 1 December 1969https://pubs.acs.org/doi/10.1021/bi00840a003https://doi.org/10.1021/bi00840a003research-articleACS PublicationsRequest reuse permissionsArticle Views225Altmetric-Citations27LEARN 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
Bronchopulmonary infection due to Branhamella catarrhalis: 11 cases assessed by transtracheal puncture. (1978)

Transtracheal punctures were performed in 193 miners of anthracosilicotic coal who presented with an acute exacerbation of chronic bronchitis. The transtracheal aspirates were bacteriologically positive in 104 patients. Branhamella catarrhalis was isolated in 15 patients; 10 of these responded to chemotherapy, as shown by the resolution of all symptoms and the disappearance of the organism on a repeat transtracheal puncture performed 48 hours after the end of treatment. One ampicillin-treated patient, whose bronchial secretions yielded a beta-lactamase-producing B catarrhalis, showed no improvement. But subsequent treatment with cefuroxime was followed by clinical and bacteriological recovery. B catarrhalis probably acted as an opportunistic respiratory pathogen in these patients, who were probably compromised hosts in view of their clinical history. B catarrhalis normally responds to the penicillins commonly used for respiratory infections, but if treatment fails a transtracheal puncture is essential to identify the strain and determine an appropriate antibiotic.
Visualization of the intracellular behavior of HIV in living cells (2002)

To track the behavior of human immunodeficiency virus (HIV)-1 in the cytoplasm of infected cells, we have tagged virions by incorporation of HIV Vpr fused to the GFP. Observation of the GFP-labeled particles in living cells revealed that they moved in curvilinear paths in the cytoplasm and accumulated in the perinuclear region, often near the microtubule-organizing center. Further studies show that HIV uses cytoplasmic dynein and the microtubule network to migrate toward the nucleus. By combining GFP fused to the NH2 terminus of HIV-1 Vpr tagging with other labeling techniques, it was possible to determine the state of progression of individual particles through the viral life cycle. Correlation of immunofluorescent and electron micrographs allowed high resolution imaging of microtubule-associated structures that are proposed to be reverse transcription complexes. Based on these observations, we propose that HIV uses dynein and the microtubule network to facilitate the delivery of the viral genome to the nucleus of the cell during early postentry steps of the HIV life cycle.
PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity (2003)

PKClambda is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. Induction of the hepatic expression of Srebp1c and of its target genes involved in fatty acid/triglyceride synthesis by fasting and refeeding or by hepatic expression of an active form of PI3K was inhibited in L-lambdaKO mice compared with that in control animals. Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. Restoration of PKClambda expression in the liver of L-lambdaKO mice with the use of adenovirus-mediated gene transfer corrected the metabolic abnormalities of these animals. Hepatic PKClambda is thus a determinant of hepatic lipid content and whole-body insulin sensitivity.
Characterization of the substance P receptor in rat brain cortex membranes and the inhibition of radioligand binding by guanine nucleotides. (1983)

Rat brain cortex membranes bind to a conjugate of substance P and 125I-labeled Bolton-Hunter reagent, and this binding can be inhibited by a low concentration of substance P (Kd = 1.2 +/- 0.4 X 10(-8) M). This binding is reversible and saturable (0.5 +/- 0.1 pmol of binding sites/mg of protein). Fragments of substance P as small as the carboxyl-terminal hexapeptide can inhibit the binding although their potency decreases with the decrease in the length of the peptides. The binding affinities of smaller peptides or peptides in which the carboxyl-terminal amide or amino acids are removed are drastically reduced. Biologically active analogs of substance P, physalaemin, eledoisin, substance P methyl ester, [D-Ala0]hepta(5-11)substance P, kassinin, and the eledoisin-related hexapeptide also can inhibit the binding. However, the binding is not inhibited by polypeptides structurally unrelated to substance P or by amine hormones/neurotransmitters. The binding affinities of biologically active peptides to rat brain cortex membranes are almost identical with their affinities for rat parotid cells which we previously determined. Furthermore, the recently described substance P antagonist, [D-Pro, D-Trp]substance P, inhibits the binding of the 125I-labeled substance P derivative to brain cortex membranes and to parotid cells equally well. These results suggest that the substance P receptors in the brain cortex and the parotid gland are similar. The brain cortex membrane binding of the 125I-labeled substance P derivative can be inhibited by micromolar concentrations of GTP, GDP, and their analogs. ITP and IDP were less active. Adenine and pyridine nucleotides were inactive.
The role of adenosine A2a receptors in regulating GABAergic synaptic transmission in striatal medium spiny neurons (1996)

We demonstrated an adenosine A,, receptor-mediated disinhibition of medium spiny projection neurons using intracellular recording and the whole-cell patch-clamp recording applied to these cells, visually identified in thin rat striatal slices. The A,, receptor agonist 2-b-(2-carboxyethyl) phenylethylaminol-5'-Nethylcarboxamido adenosine (CGS-21680; 0.3-l 0 PM) suppressed GABAergic synaptic transmission onto these cells in a manner inhibited by the A,, receptor-selective antagonist (E)-8-(3,4-dimethoxystytyl)-l,3-dipropyl-7-methylxanthine (0.1-l .O PM).
Isolation and characterization of cDNA clones encoding pathogenesis-related proteins from tobacco mosaic virus infected tobacco plants (1987)

Infection of the tobacco cultivar Samsun NN by tobacco mosaic virus (TMV) results in a hypersensitive response. During this defense reaction several host encoded proteins, known as pathogenesis-related proteins (PR-proteins), are induced. Poly(A)+ RNA from TMV infected tobacco plants was used to construct a cDNA library. Thirty two cDNA clones were isolated and after digestion with different restriction endonucleases, twenty clones were found to code for PR-1a, six clones for PR-1b, and four clones for PR-1c. Two independent cDNA clones of each class were further characterized by DNA sequence analysis. All clones analyzed contained the 138 amino acid coding regions of their respective mature proteins, but only partial sequences of the signal peptides. Minor differences between the nucleotide sequences for clones belonging to the same class were detected. Comparison of the amino acid sequence for PR-1a deduced from its nucleotide sequence with published data obtained by Edman degradation of the protein showed four differences. Analysis of the 3' ends of the cDNA clones indicates that various alternate poly(dA) addition sites are used. Southern blot analysis using these cDNAs as probes suggests the presence of multiple PR-protein genes in the genomes of tobacco and tomato plants.
A recombinant, soluble, single-chain class I major histocompatibility complex molecule with biological activity. (1992)

Heterodimeric class I major histocompatibility complex molecules, which consist of a 45-kDa heavy-chain and a 12-kDa beta 2-microglobulin (beta 2m) light chain, bind endogenously synthesized peptides for presentation to antigen-specific T cells. We have synthesized a gene encoding a single-chain, soluble class I molecule derived from mouse H-2Dd, in which the carboxyl terminus of beta 2m is linked via a peptide spacer to the amino terminus of the heavy chain. The chimeric protein is secreted efficiently from transfected L cells, is thermostable, and when loaded with an appropriate antigenic peptide, stimulates an H-2Dd-restricted antigen-specific T-cell hybridoma. Thus, functional binding of peptide does not require the complete dissociation of beta 2m, implying that a heavy chain/peptide complex is not an obligate intermediate in the assembly of the heavy-chain/beta 2m/peptide heterotrimer. Single-chain major histocompatibility complex molecules uniformly loaded with peptide have potential uses for structural studies, toxin or fluor conjugates, and vaccines.
Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene. (1996)

The human retinoblastoma susceptibility gene, a member of the tumor suppressor gene family, is located on chromosome 13q14.12-13q14.2 and consists of 27 exons that are distributed over 180 kb. This study shows that intron 17, the largest in size, consisting of nearly 72,000 bp, contains an open reading frame encoding a novel G protein-coupled receptor in the reverse orientation relative to the transcription of the retino-blastoma susceptibility gene. Correction of a frameshift mutation revealed that this novel G protein-coupled receptor is the human homolog of a chicken T-cell-specific receptor cDNA. This is an additional description of an actively transcribed protein-encoding gene positioned within an intron of another gene, suggesting that introns can have important structural functions.
The pro region of human neutrophil defensin contains a motif that is essential for normal subcellular sorting (1995)

Human defensins (human neutrophil peptides) HNP 1-3 are 29-30 amino acid antibiotic and cytotoxic peptides highly abundant in the cytoplasmic granules of polymorphonuclear leukocytes. The peptides are produced from 94 amino acid (aa) prepropeptides by proteolytic cleavage of the signal sequence and stepwise removal of the 44-45 aa anionic propiece. To study the role of the propiece, we constructed five in-frame deletions in preproHNP-1 cDNA between the signal peptidase site and the amino-terminus of the mature defensin region (aa 21-64). The wild type HNP-1 cDNA and the deletion mutants were ligated into the pBabe-Neo retroviral vector, expressed in GP+E86 packaging derivative of NIH 3T3 cells, then transduced into the 32D cl3 granulocytic cell line. For each construction and both cell lines, we measured the accumulation of the various defensin forms in cells and media by 24-hour labeling or pulse-chase with 35S-cysteine- and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Deletions in the amino-terminal two-fifths of the propiece, delta 21-28 and delta 21-38, had only minor effects on defensin biosynthesis in both cell lines and did not interfere with the accumulation of mature defensin in the granules of 32D cl3 cells. Deletions in the carboxyterminal three-fifths of the propiece (delta 21-51 and delta 21-64) diminished net defensin synthesis, blocked constitutive secretion of prodefensin in both cell lines, and interfered with defensin accumulation in cytoplasmic granules of 32D cl3 cells. These effects were reproduced by the smaller deletion delta 40-51, which contains highly conserved secondary structure. The propiece segment 40-51 appears to be essential for the subcellular trafficking and sorting of HNP-1 defensin.
Mechanism of endocytosis of CD33/Siglec-3: role of ITIMs, tyrosine phosphorylation, and monoubiquitylation (2006)

Thesis (Ph. D.)--University of Washington, 2006.
Dependence of pulmonary absorption kinetics on aerosol particle size. (1986)

To determine the effect of aerosol particle size upon absorption from the respiratory tract (RT), solid, polydisperse disodium fluorescein aerosols (MMDae 1.1, 3.5 and 4.4 micron) were delivered under the same respiratory regime direct to the RT of 2 Beagle dogs by positive pressure ventilation using a purpose designed administration system. Subsequent to aerosol administration the amount of fluorescein absorbed as a function of time was estimated from plasma concentration versus time and intravenous control data using a modified Loo Riegelman method. Maximum fractional deposition within the RT occurred with 3.5 micron aerosol. Fluorescein was absorbed rapidly from the RT according to an apparent first-order process the rate constant for which was independent of particle size and possibly regional deposition. Average values for absorption half lives in the 2 dogs were 17.3 and 11.4 minutes.
Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study (2005)

A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients.
Innate Immune Pattern Recognition: A Cell Biological Perspective (2015)

Receptors of the innate immune system detect conserved determinants of microbial and viral origin. Activation of these receptors initiates signaling events that culminate in an effective immune response. Recently, the view that innate immune signaling events rely on and operate within a complex cellular infrastructure has become an important framework for understanding the regulation of innate immunity. Compartmentalization within this infrastructure provides the cell with the ability to assign spatial information to microbial detection and regulate immune responses. Several cell biological processes play a role in the regulation of innate signaling responses; at the same time, innate signaling can engage cellular processes as a form of defense or to promote immunological memory. In this review, we highlight these aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol.
Accelerating genome editing in CHO cells using CRISPR Cas9 and CRISPy, a web‐based target finding tool (2014)

Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry as a host for the production of complex pharmaceutical proteins. Thus genome engineering of CHO cells for improved product quality and yield is of great interest. Here, we demonstrate for the first time the efficacy of the CRISPR Cas9 technology in CHO cells by generating site-specific gene disruptions in COSMC and FUT8, both of which encode proteins involved in glycosylation. The tested single guide RNAs (sgRNAs) created an indel frequency up to 47.3% in COSMC, while an indel frequency up to 99.7% in FUT8 was achieved by applying lectin selection. All eight sgRNAs examined in this study resulted in relatively high indel frequencies, demonstrating that the Cas9 system is a robust and efficient genome-editing methodology in CHO cells. Deep sequencing revealed that 85% of the indels created by Cas9 resulted in frameshift mutations at the target sites, with a strong preference for single base indels. Finally, we have developed a user-friendly bioinformatics tool, named "CRISPy" for rapid identification of sgRNA target sequences in the CHO-K1 genome. The CRISPy tool identified 1,970,449 CRISPR targets divided into 27,553 genes and lists the number of off-target sites in the genome. In conclusion, the proven functionality of Cas9 to edit CHO genomes combined with our CRISPy database have the potential to accelerate genome editing and synthetic biology efforts in CHO cells.
Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. Interference of tissue-derived components. (1986)

The influence of endotoxin-induced elevated plasma levels of the fast-acting inhibitor of plasminogen activator (PA-inhibitor) on thrombolysis was investigated in rabbits with a jugular vein thrombus. Infusion of human tissue-type plasminogen activator (t-PA) produced similar degrees of thrombolysis in control and endotoxin-treated rabbits, although no free t-PA could be demonstrated in plasma of endotoxin-treated animals. Infusion of t-PA in an extracorporeal arteriovenous shunt resulted in loss of thrombolytic activity in endotoxin-treated animals but not in control animals. Blood clots superfused in vitro with mixtures of t-PA and normal plasma lysed in contrast to clots superfused with t-PA and PA-inhibitor-rich plasma. However, addition of rabbit lung slices to the plasma surrounding the blood clot, reversed the inhibition of thrombolysis by PA-inhibitor-rich plasma. This indicates that tissue-derived factor(s) are involved in the regulation of in vivo thrombolysis. These hypothetical factor(s) are, however, very unstable in plasma, which has thus far precluded their further characterization.
Thiol-beta-lactamase: replacement of the active-site serine of RTEM beta-lactamase by a cysteine residue. (1982)

We describe a procedure by which the codon (AGC) for the active-site serine-70 of pBR322 beta-lactamase (penicillinase, penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) is altered to that for cysteine (TGC). The pertinent nucleotide bases, A-G-C-A, positions 410-413, of pBR322 are excised by treating a limited HgiAI digest of pBR322 with the 3' leads to 5' exonuclease of T4 DNA polymerase. The new sequence, T-G-C-A, is inserted in two steps. First, the Kpn I molecular linker d(T-G-G-T-A-C-C-A) is ligated into the gap described above. The internal sequence G-T-A-C is then excised enzymatically with Kpn I and T4 DNA polymerase and the molecule is recircularized. This mutant gene, which codes for a thiol-beta-lactamase, confers on Escherichia coli K-12 hosts an ampicillin resistance that is reduced compared with that given by pBR322 yet is greater than that of E. coli lacking any intact beta-lactamase gene. Cell-free extracts of E. coli strains hosting the thiol-beta-lactamase gene possess a p-chloromercuribenzoate-sensitive beta-lactamase activity.
FDA Report: Eculizumab (Soliris®) for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria (2008)

On March 16, 2007, eculizumab (Soliris; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion-dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.
Apoptosis in Human Acute Myocardial Infarction (1997)

This study provides evidence that in addition to overt necrosis, a subset of myocytes undergo apoptosis during ischemia-reperfusion injury. Apoptosis may provide a new target for cardioprotection during evolving AMI in humans.
“Lithium-Free” Thin-Film Battery with In Situ Plated Li Anode (2000)

The "Li‐free" thin‐film battery with the cell configuration Li diffusion blocking overlayer/Cu/solid lithium electrolyte is activated by in situ plating of metallic Li at the Cu anode current collector during the initial charge. Electrochemical cycling between 4.2 and 3.0 V is demonstrated over 1000 cycles at or over 500 cycles at . As corroborated by scanning electron microscopy during electrochemical cycling, the overlayer is imperative for a high cycle stability; otherwise the plated Li rapidly develops a detrimental morphology, and the battery loses most of its capacity within a few cycles. The Li‐free thin‐film battery retains the high potential of a Li cell while permitting its fabrication in air without the complications of a metallic Li anode. Thus, the Li‐free thin‐film battery survives solder reflow conditions, simulated by a rapid heating to 250°C for 10 min in air followed by quenching to room temperature, without any signs of degradation. © 2000 The Electrochemical Society. All rights reserved.