gebhart/patrepeval huggingface dataset:
Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism (2002)

Peroxisomes function in beta-oxidation of very long and long-chain fatty acids, dicarboxylic fatty acids, bile acid intermediates, prostaglandins, leukotrienes, thromboxanes, pristanic acid, and xenobiotic carboxylic acids. These lipids are mainly chain-shortened for excretion as the carboxylic acids or transported to mitochondria for further metabolism. Several of these carboxylic acids are slowly oxidized and may therefore sequester coenzyme A (CoASH). To prevent CoASH sequestration and to facilitate excretion of chain-shortened carboxylic acids, acyl-CoA thioesterases, which catalyze the hydrolysis of acyl-CoAs to the free acid and CoASH, may play important roles. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). PTE-2 is ubiquitously expressed and induced at mRNA level by treatment with the peroxisome proliferator WY-14,643 and fasting. Induction seen by these treatments was dependent on the peroxisome proliferator-activated receptor alpha. Recombinant PTE-2 showed a broad chain length specificity with acyl-CoAs from short- and medium-, to long-chain acyl-CoAs, and other substrates including trihydroxycoprostanoyl-CoA, hydroxymethylglutaryl-CoA, and branched chain acyl-CoAs, all of which are present in peroxisomes. Highest activities were found with the CoA esters of primary bile acids choloyl-CoA and chenodeoxycholoyl-CoA as substrates. PTE-2 activity is inhibited by free CoASH, suggesting that intraperoxisomal free CoASH levels regulate the activity of this enzyme. The acyl-CoA specificity of recombinant PTE-2 closely resembles that of purified mouse liver peroxisomes, suggesting that PTE-2 is the major acyl-CoA thioesterase in peroxisomes. Addition of recombinant PTE-2 to incubations containing isolated mouse liver peroxisomes strongly inhibited bile acid-CoA:amino acid N-acyltransferase activity, suggesting that this thioesterase can interfere with CoASH-dependent pathways. We propose that PTE-2 functions as a key regulator of peroxisomal lipid metabolism.
Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones (1991)

Novel pyrido[2,3-b][1,4]benzodiazepinones (I), pyrido[2,3-b][1,5]benzodiazepinones (II), and dipyrido[3,2-b:2',3'-e][1,4]diazepinones (III) were found to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in vitro at concentrations as low as 35 nM. In all three series, small substituents (e.g., methyl, ethyl, acetyl) are preferred at the lactam nitrogen, whereas slightly larger alkyl moieties (e.g., ethyl, cyclopropyl) are favored at the other (N-11) diazepinone nitrogen. In general, lipophilic substituents are preferred on the A ring, whereas substitution on the C ring generally reduces potency relative to the corresponding compounds with no substituents on the aromatic rings. Maximum potency is achieved with methyl substitution at the position ortho to the lactam nitrogen atom; however, in this case an unsubstituted lactam nitrogen is preferred. Additional substituents on the A ring can be readily tolerated. The dipyridodiazepinone derivative 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e] [1,4]diazepin-6-one (96, nevirapine) is a potent (IC50 = 84 nM) and and selective non-nucleoside inhibitor of HIV-1 reverse transcriptase, and has been chosen for clinical evaluation.
Segment Concentration Profile of Myoglobin Adsorbed to Metal Ion Chelating Lipid Monolayers at the Air−Water Interface by Neutron Reflection (2002)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTSegment Concentration Profile of Myoglobin Adsorbed to Metal Ion Chelating Lipid Monolayers at the Air−Water Interface by Neutron ReflectionM. S. Kent, H. Yim, D. Y. Sasaki, J. Majewski, G. S. Smith, K. Shin, S. Satija, and B. M. OckoView Author Information Sandia National Laboratories, Albuquerque, New Mexico Los Alamos National Laboratories, Los Alamos, New Mexico National Institute of Standards and Technology, Gaithersburg, Maryland Brookhaven National Laboratories, Brookhaven, New York Cite this: Langmuir 2002, 18, 9, 3754–3757Publication Date (Web):March 29, 2002Publication History Received17 September 2001Revised15 January 2002Published online29 March 2002Published inissue 1 April 2002https://pubs.acs.org/doi/10.1021/la011440mhttps://doi.org/10.1021/la011440mbrief-reportACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views191Altmetric-Citations24LEARN 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 SUBJECTS:Adsorption,Ions,Layers,Lipids,Optical properties Get e-Alerts
Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients (2013)

High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.
Fusion of sequence elements from non-anchored proteins to generate a fully functional signal for glycophosphatidylinositol membrane anchor attachment. (1991)

Glycophosphatidylinositol (GPI) membrane anchor attachment is directed by a cleavable signal at the COOH terminus of the protein. The complete lack of homology among different GPI-anchored proteins suggests that this signal is of a general nature. Previous analysis of the GPI signal of decay accelerating factor (DAF) suggests that the minimal requirements for GPI attachment are (a) a hydrophobic domain and (b) a cleavage/attachment site consisting of a pair of small residues positioned 10-12 residues NH2-terminal to a hydrophobic domain. As an ultimate test of these rules we constructed four synthetic GPI signals, meeting these requirements but assembled entirely from sequence elements not normally involved in GPI attachment. We show that these synthetic signals are able to direct human growth hormone (hGH), a secreted protein, to the plasma membrane via a GPI anchor. Our results indicate that different hydrophobic sequences, derived from either the prolactin or hGH NH2-terminal signal peptide, can be linked to different cleavage sites via different hydrophilic spacers to produce a functional GPI signal. These data confirm that the only requirements for GPI-anchoring are a pair of small residues positioned 10-12 residues NH2 terminal to a hydrophobic domain, no other structural motifs being necessary.
Intra-arterial thrombolysis (2001)

Intra-arterial (IA) thrombolysis is an emerging treatment strategy for acute ischemic stroke. In IA thrombolysis, the cervicocephalic arterial tree is traversed with an endovascular microcatheter delivery system, the catheter port is positioned immediately within and adjacent to the offending thrombus, and fibrinolytic agents are infused directly into the clot. This delivery technique permits high concentrations of lytic agent to be applied to the clot while minimizing systemic exposure. Early open series suggested that IA thrombolysis achieves higher recanalization rates than i.v. thrombolysis. The first randomized Phase III trial of IA thrombolysis, the Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial, confirmed this promise, showing that IA therapy begun up to 6 hours after symptom onset was associated with higher recanalization rates and better clinical outcomes, with acceptable hemorrhage rates. MRI studies have provided striking imaging evidence of the potential beneficial effects of IA therapy, showing not only rescue of regions of diffusion-perfusion mismatch but also normalization and salvage of some tissues with pretreatment bioenergetic failure evidenced by early diffusion abnormality. The Emergency Management of Stroke Bridging Trial demonstrated the feasibility of combined i.v. and intra-arterial thrombolysis. Intra-arterial thrombolysis is a promising treatment strategy for acute ischemic stroke. In coming years, IA thrombolysis, alone or in combination with endovascular mechanical reperfusion techniques, is likely to be increasingly refined and validated and to become a widely accepted therapy for acute ischemic stroke.
The porcine melanocortin-5 receptor (MC5R) gene: polymorphisms, linkage and physical mapping. (2000)

Source/description: The melanocortin-5 receptor mediates the effects of adrenocorticotropic hormone (ACTH) or melanocortin stimulating hormones (MSH) on exocrine gland functions, including theromoregulation, immunomodulation, and sexual behaviour. Primers were designed in sequence regions conserved among the human, rat and bovine MC5R genes (Genbank accession nos U08353, L27081 and AJ002024, respectively). The consensus coding sequence (884 bp) of the porcine PCR products showed 82 % nucleotide identity and 81.2% amino acid identity to the corresponding human sequence. The porcine MC5R sequence has been submitted to GenBank (accession number AF133793). Two single nucleotide polymorphisms were found by sequence analyses of the PCR products amplified from the pooled DNAs of individual pigs from several different breeds.
Metal ion activation of galactosyltransferase. (1976)

Galactosyltransferase, which functions as the catalytic component of lactose synthase and in the glycosylation of glycoproteins, has been previously reported to have an absolute dependence on Mn2+ for activity, with a Kd for Mn2+ (10(-3) M) 2 to 3 orders of magnitude greater than the physiological range of Mn2+ concentrations (v 10(-6) M). Reinvestigation of the metal ion dependence of this enzyme has shown that Zn2+, Cd2+, Fe2+, Co2+, and Pr3+ also produce activation, although with lower activities at saturation than that attained with Mn2+. Velocity against metal ion concentration curves for all metals, including Mn2+, are sigmoid, suggesting the presence of two or more activating metal binding sites on the enzyme. The presence of two sites is confirmed by studies using both Mn2+ and Ca2+. While galactosyltransferase is inactive in the presence of Ca2+ alone, at low concentrations of Mn2+ (10(-5) M), enzyme activity is stimulated by Ca2+. A more detailed investigation by steady state kinetics has revealed that there is a tight binding site for Mn2+ (site I: Kd of 2 X 10(-6) M) from which Ca2+ is excluded, and a site at which Ca2+ can replace Mn2+ (site II: Kd for Ca2+ of 1.76 X 10(-3) M), to which metal binding has a specific synergistic effect on UDP-galactose binding, possibly as a result of the formation of an enzyme-Ca2+-UDP-galactose bridge complex. The site I Mn2+, site II Ca2+-activated enzyme has a maximum velocity similar to that of the Mn2+-activated enzyme, and is the enzyme form that must act in lactose synthesis in vivo. A trypsin-degraded form of galactose transferase (galactosyltransferase-T) (Powell, J.T., and Brew, K. (1974) Eur. J. Biochem. 48, 217-228) appears to lack site I and is activated by Ca2+ in the absence of Mn2+.
Analysis of Volatile Organic Compounds in Air with a Micro Ion Trap Mass Analyzer (2003)

Analysis of several volatile organic compounds in air has been demonstrated with a micro ion trap mass analyzer equipped with a semipermeable membrane sampling inlet. MS/MS of selected compounds was also shown to be feasible with the miniature ion trap and could be used to improve sensitivity by reducing background noise.
Identification of a novel picornavirus related to cosaviruses in a child with acute diarrhea (2008)

Diarrhea, the third leading infectious cause of death worldwide, causes approximately 2 million deaths a year. Approximately 40% of these cases are of unknown etiology. We previously developed a metagenomic strategy for identification of novel viruses from diarrhea samples. By applying mass sequencing to a stool sample collected in Melbourne, Australia from a child with acute diarrhea, one 395 bp sequence read was identified that possessed only limited identity to known picornaviruses. This initial fragment shared only 55% amino acid identity to its top BLAST hit, the VP3 protein of Theiler's-like virus, suggesting that a novel picornavirus might be present in this sample. By using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, 6562 bp of the viral genome was sequenced, which includes the entire putative polyprotein. The overall genomic organization of this virus was similar to known picornaviruses. Phylogenetic analysis of the polyprotein demonstrated that the virus was divergent from previously described picornaviruses and appears to belong to the newly proposed picornavirus genus, Cosavirus. Based on the analysis discussed here, we propose that this virus represents a new species in the Cosavirus genus, and it has tentatively been named Human Cosavirus E1 (HCoSV-E1).
Flexible a-Si:H Position-Sensitive Detectors (2005)

Flexible and large area (5 mm /spl times/80 mm with an active length of 70 mm) position-sensitive detectors (PSDs) deposited onto polymeric substrates (polyimide-Kapton VN) have been fabricated. The optimized structure presented is based on a heterojunction of amorphous silicon (a-Si:H)/ZnO:Al. The sensors were characterized by spectral response, photocurrent dependence as a function of light intensity, and position detection measurements. The set of data obtained on one-dimensional PSDs based on the heterojunction show excellent performances with a maximum spectral response of 0.12 A/W at 500 nm and a nonlinearity of /spl plusmn/10% over 70-mm length. The produced sensors present a nonlinearity higher than those ones produced on glass substrates, due to the different thermal coefficients exhibited by the polymer and the a-Si:H film. In order to prove this behavior, it was measured the defect density obtained by the constant photocurrent method on a-Si:H thin films deposited on polymeric substrates and bent with different radii of curvature.
Prediction of the Coding Sequences of Unidentified Human Genes. XIX. The complete Sequences of 100 New cDNA Clones from Brain Which Code for Large Proteins in vitro (2000)

As an extension of our human cDNA project for accumulating sequence information on the coding sequences of unidentified genes, we here present the entire sequences of 100 cDNA clones of unidentified genes, named KIAA1673-KIAA1772, from three sets of size-fractionated cDNA libraries derived from human adult whole brain, hippocampus, and fetal whole brain. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here were 4.9 kb and 2.7 kb (corresponding to 895 amino acid residues), respectively. By computer-assisted analysis of the deduced amino acid sequences, 44 predicted gene products were classified into five functional categories of proteins relating to cell signaling/communication, nucleic acid management, cell structure/motility, protein management, and metabolism. Furthermore, the expression profiles of the genes were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse-transcription-coupled polymerase chain reaction, the products of which were quantified by enzyme-linked immunosorbent assay.
La moral, la ética y la bioética como limitantes sociales a la protección de las invenciones por la vía de las patentes (2006)

El presente trabajo tiene como finalidad demostrar la relacion entre la moral, la etica, la bioetica y la proteccion de las invenciones por la via de las patentes, realizando para ello un estudio de derecho comparado entre las legislaciones sobre la materia, con especial enfasis en la legislacion latinoamericana, pretendiendo comprobar la presencia constante en el derecho invencional iberoamericano de las nociones bioeticas para limitar la proteccion de las invenciones contrarias a las mismas, y la coincidencia entre estas de las exclusiones fundadas en razones morales o bioeticas.
Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers (2009)

Developing an immunogen that elicits broadly neutralizing antibodies (bNAbs) is an elusive but important goal of HIV vaccine research, especially after the recent failure of the leading T cell based HIV vaccine in human efficacy trials. Even if such an immunogen can be developed, most animal model studies indicate that high serum neutralizing concentrations of bNAbs are required to provide significant benefit in typical protection experiments. One possible exception is provided by the anti-glycan bNAb 2G12, which has been reported to protect macaques against CXCR4-using SHIV challenge at relatively low serum neutralizing titers. Here, we investigated the ability of 2G12 administered intravenously (i.v.) to protect against vaginal challenge of rhesus macaques with the CCR5-using SHIV(SF162P3). The results show that, at 2G12 serum neutralizing titers of the order of 1:1 (IC(90)), 3/5 antibody-treated animals were protected with sterilizing immunity, i.e. no detectable virus replication following challenge; one animal showed a delayed and lowered primary viremia and the other animal showed a course of infection similar to 4 control animals. This result contrasts strongly with the typically high titers observed for protection by other neutralizing antibodies, including the bNAb b12. We compared b12 and 2G12 for characteristics that might explain the differences in protective ability relative to neutralizing activity. We found no evidence to suggest that 2G12 transudation to the vaginal surface was significantly superior to b12. We also observed that the ability of 2G12 to inhibit virus replication in target cells through antibody-mediated effector cell activity in vitro was equivalent or inferior to b12. The results raise the possibility that some epitopes on HIV may be better vaccine targets than others and support targeting the glycan shield of the envelope.
Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation (1992)

Platelets subjected to elevated levels of fluid shear stress in the absence of exogenous agonists will aggregate. Shear stress-induced aggregation requires von Willebrand factor (vWF) multimers, extracellular calcium (Ca2+), adenosine diphosphate (ADP), and platelet membrane glycoprotein (GP)Ib and GPIIb-IIIa. The sequence of interaction of vWF multimers with platelet surface receptors and the effect of these interactions on platelet activation have not been determined. To elucidate the mechanism of shear stress-induced platelet aggregation, suspensions of washed platelets were subjected to different levels of uniform shear stress (15 to 120 dyne/cm2) in an optically modified cone and plate viscometer. Cytoplasmic ionized calcium ([Ca2+]i) and aggregation of platelets were monitored simultaneously during the application of shear stress; [Ca2+]i was measured using indo-1 loaded platelets and aggregation was measured as changes in light transmission. Basal [Ca2+]i was approximately 60 to 100 nmol/L. An increase of [Ca2+]i (up to greater than 1,000 nmol/L) was accompanied by synchronous aggregation, and both responses were dependent on the shear force and the presence of vWF multimers. EGTA chelation of extracellular Ca2+ completely inhibited vWF-mediated [Ca2+]i and aggregation responses to shear stress. Aurin tricarboxylic acid, which blocks the GPIb recognition site on the vWF monomer, and 6D1, a monoclonal antibody to GPIb, also completely inhibited platelet responses to shear stress. The tetrapeptide RGDS and the monoclonal antibody 10E5, which inhibit vWF binding to GPIIb-IIIa, partially inhibited shear stress-induced [Ca2+]i and aggregation responses. The combination of creatine phosphate/creatine phosphokinase, which converts ADP to adenosine triphosphate and blocks the effect of ADP released from stimulated platelets, inhibited shear stress-induced platelet aggregation without affecting the increase of [Ca2+]i. Neither the [Ca2+]i nor aggregation response to shear stress was inhibited by blocking platelet cyclooxygenase metabolism with acetylsalicylic acid. These results indicate that GPIb and extracellular Ca2+ are absolutely required for vWF-mediated [Ca2+]i and aggregation responses to imposed shear stress, and that the interaction of vWF multimers with GPIIb-IIIa potentiates these responses. Shear stress-induced elevation of platelet [Ca2+]i, but not aggregation, is independent of the effects of release ADP, and both responses occur independently of platelet cyclooxygenase metabolism. These results suggest that shear stress induces the binding of vWF multimers to platelet GPIb and this vWF-GPIb interaction causes an increase of [Ca2+]i and platelet aggregation, both of which are potentiated by vWF binding to the platelet GPIIb-IIIa complex.
Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN- gamma . (1988)

Acute experimental allergic encephalomyelitis (EAE) was induced in C57BL/6J and SJL/J mice by injection of isologous spinal cord homogenate given in conjunction with Bordetella pertussis and Freund's adjuvant. SJL/J mice showed a highly aggressive and 100% lethal form of the disease; C57BL/6J mice were much less susceptible as they had low morbidity rates (20 to 40%), low disease scores, and mostly no mortality. Treatment of these low susceptibility mice with neutralizing mAb against IFN-gamma caused an increase in morbidity rates as well as significant mortality (up to 80%). Similar antibody treatment did not affect the course of the disease in the high susceptibility SJL/J mice. However, treatment of these mice with IFN-gamma resulted in reduced morbidity and mortality. A similar but less pronounced inhibition of the disease in SJL/J mice could be obtained by administration of IFN-alpha/beta or by acute infection with lactate dehydrogenase virus. The results indicate that endogenous as well as exogenous IFN can exert a down-regulating effect on the development of EAE. They also indicate that endogenous IFN-gamma is produced during the development of EAE and plays a disease-limiting role.