gebhart/patrepeval huggingface dataset:
Phosphoinositide 3-kinase forms a complex with platelet membrane glycoprotein Ib-IX-V complex and 14-3-3ζ (2000)

The binding of von Willebrand factor (vWF) to glycoprotein (GP) Ib-IX-V stimulates transmembrane signaling events that lead to platelet adhesion and aggregation. Recent studies have revealed that the signaling protein 14-3-3ζ binds directly to the cytoplasmic domain of GP Ib. In this study, the dynamic association of 14-3-3ζ with GP Ib-IX, the phosphoinositide 3-kinase (PI 3-kinase), or both, was investigated in resting, thrombin, or vWF and botrocetin-stimulated platelets by analysis of discrete subcellular fractions. Results of this study demonstrate maximal coimmunoprecipitation of 14-3-3ζ with GP Ib-IX in the nonstimulated cytosolic fraction and in the actin cytoskeletal fraction of thrombin- or vWF-stimulated human platelets. Immunoprecipitated 14-3-3ζ or GP Ib from cytosolic fractions contained PI 3-kinase enzyme activity and an 85-kd polypeptide recognized by antibodies to the p85 subunit of PI 3-kinase. After platelet activation, the level of association between these species decreased in the cytosolic fraction. However, increased complex formation between 14-3-3ζ and GP Ib-IX and between PI 3-kinase and GP Ib-IX was detected in actin cytoskeletal fractions derived from thrombin- or vWF-stimulated platelets. Recombinant glutathione S-transferase-14-3-3ζ fusion protein (14-3-3ζ–GST) inhibited affinity-captured PI 3-kinase enzyme activity up to 70% at 2 μmol/L 14-3-3ζ–GST. However, increasing concentrations up to 5 μmol/L 14-3-3ζ–GST resulted in the 3-fold enhancement of PI 3-kinase enzyme activity. We propose that the association between PI 3-kinase and 14-3-3ζ with GP Ib-IX serves to promote the rapid translocation of these signaling proteins to the activated cytoskeleton, thereby regulating the formation of 3-position phosphoinositide-signaling molecules in this subcellular compartment.
Transcriptional activation of endothelial cell integrin αv by protein kinase C activator 12(S)-HETE (1995)

Previous work demonstrated that 12(S)-HETE [12(S)-hydroxyeicosatetraenic acid], a lipoxygenase metabolite of arachidonic acid, stimulates the surface expression of integrin alpha v beta 3 on mouse lung vascular endothelial cells (CD clone 3) in a post-transcriptional and protein kinase C (PKC)-dependent fashion. In this study we examined the effect of 12(S)-HETE on the expression of integrin receptors alpha v beta 3 and alpha 5 beta 1 in a different clone of a mouse endothelial cell population derived from lung microvasculature (designated CD clone 4). The results indicated that 12(S)-HETE transcriptionally activates the gene expression of integrin alpha v as assessed by quantitative reverse transcription/polymerase chain reaction/Southern hybridization, RNase protection assay, solution hybridization, and northern blotting. The induction of alpha v mRNA occurred within 1 hour, peaked at approximately 4 hours (2- to 4-fold increase), persisted for up to 16 hours, and thereafter gradually declined. The PKC activator phorbol 12-myristate 13-acetate (PMA) induced the alpha v mRNA, in a similar way. 12(S)-HETE treatment did not, in contrast, alter the mRNA levels of integrin subunit alpha 5 or beta 1. The induction of alpha v mRNA appeared to be protein synthesis-independent, since cycloheximide did not alter the 12(S)-HETE effect. 12(S)-HETE also did not appear to alter the mRNA half-life of alpha v. On the other hand, 12(S)-HETE-induced increase in alpha v mRNA levels was PKC-dependent, since pretreatment of CD clone 4 cells with calphostin C significantly inhibited 12(S)-HETE-increased alpha v mRNA. Nuclear runoff experiments revealed that the increase in alpha v mRNA results from an enhanced gene transcription. Facilitated alpha v gene transcription resulted in an increased surface expression of alpha v beta 3 protein, which resulted in an increased cell adhesion to vitronectin. The above observations, in conjunction with our previous experimental data, suggest that 12(S)-HETE may employ diverse mechanisms to stimulate the integrin alpha v beta 3 expression in vascular endothelial cells, which could play important roles in tumor cell adhesion, angiogenesis, hemostasis, and many other vascular events.
Glomerular Activation of the Lectin Pathway of Complement in IgA Nephropathy Is Associated with More Severe Renal Disease (2006)

IgA nephropathy (IgAN) is characterized by glomerular co-deposition of IgA and complement components. Earlier studies showed that IgA activates the alternative pathway of complement, whereas more recent data also indicate activation of the lectin pathway. The lectin pathway can be activated by binding of mannose-binding lectin (MBL) and ficolins to carbohydrate ligands, followed by activation of MBL-associated serine proteases and C4. This study examined the potential role of the lectin pathway in IgAN. Renal biopsies of patients with IgAN (n=60) showed mesangial deposition of IgA1 but not IgA2. Glomerular deposition of MBL was observed in 15 (25%) of 60 cases with IgAN and showed a mesangial pattern. All MBL-positive case, but none of the MBL-negative cases showed glomerular co-deposition of L-ficolin, MBL-associated serine proteases, and C4d. Glomerular deposition of MBL and L-ficolin was associated with more pronounced histologic damage, as evidenced by increased mesangial proliferation, extracapillary proliferation, glomerular sclerosis, and interstitial infiltration, as well as with significantly more proteinuria. Patients who had IgAN with or without glomerular MBL deposition did not show significant differences in serum levels of MBL, L-ficolin, or IgA or in the size distribution of circulating IgA. Furthermore, in vitro experiments showed clear binding of MBL to polymeric but not monomeric patient IgA, without a significant difference between both groups. Together, these findings strongly point to a role for the lectin pathway of complement in glomerular complement activation in IgAN and suggest a contribution for both MBL and L-ficolin in the progression of the disease.
Rapid Identification of Bacteria with a Disposable Colorimetric Sensing Array (2011)

Rapid identification of both species and even specific strains of human pathogenic bacteria grown on standard agar has been achieved from the volatiles they produce using a disposable colorimetric sensor array in a Petri dish imaged with an inexpensive scanner. All 10 strains of bacteria tested, including Enterococcus faecalis and Staphylococcus aureus and their antibiotic-resistant forms, were identified with 98.8% accuracy within 10 h, a clinically important time frame. Furthermore, the colorimetric sensor arrays also proved useful as a simple research tool for the study of bacterial metabolism and as an easy method for the optimization of bacterial production of fine chemicals or other fermentation processes.
Inhibition of HIV-1 Latency Reactivation by Dehydroepiandrosterone (DHEA) and an Analog of DHEA (1993)

The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Correlations in timing of sodium channel expression, epilepsy, and sudden death in Dravet syndrome (2013)

Dravet Syndrome (DS) is an intractable genetic epilepsy caused by loss-of-function mutations in SCN1A, the gene encoding brain sodium channel Nav 1.1. DS is associated with increased frequency of sudden unexpected death in humans and in a mouse genetic model of this disease. Here we correlate the time course of declining expression of the murine embryonic sodium channel Nav 1.3 and the rise in expression of the adult sodium channel Nav 1.1 with susceptibility to epileptic seizures and increased incidence of sudden death in DS mice. Parallel studies with unaffected human brain tissue demonstrate similar decline in Nav 1.3 and increase in Nav 1.1 with age. In light of these results, we introduce the hypothesis that the natural loss Nav 1.3 channel expression in brain development, coupled with the failure of increase in functional Nav 1.1 channels in DS, defines a tipping point that leads to disinhibition of neural circuits, intractable seizures, co-morbidities, and premature death in this disease.
Mobile augmented reality for cultural heritage: A technology acceptance study (2012)

We have developed a mobile augmented reality application with historical photographs and information about a historical street. We follow a design science research methodology and use an extended version of the technology acceptance model (TAM) to study the acceptance of this application. A prototype has been developed in accordance with general principles for usability design, and two surveys have been conducted. A web survey with 200 participants that watched a short video demonstration of the application to validate the adapted acceptance model, and a street survey, where 42 participants got the opportunity to try the application in a live setting before answering a similar questionnaire and provide more concrete feedback. The results show that both perceived usefulness and perceived enjoyment has a direct impact on the intention to use mobile augmented reality applications with historical pictures and information. Further a number of practical recommendations for the development and deployment of such systems are provided.
Follow‐up evaluation of a phase II prostate cancer vaccine trial (1999)

BACKGROUND A phase II trial, involving infusions of autologous dendritic cells (DC) and two human histocompatibility antigen (HLA-A2)-specific prostate-specific membrane antigen (PSMA) peptides, was recently completed. Thirty percent of the participants, including subjects with hormone-refractory metastastic disease, and those with suspected local recurrence of prostate cancer, were identified as clinical responders. This report describes the follow-up evaluation of 19 responders in the two study groups. METHODS After conclusion of the study, study participants were subjected to follow-up evaluations at 6–8-week intervals. Each responder was reevaluated for response status, and duration of response was determined. RESULTS Subjects were observed for an average of 291 days (metastastic group, group A-2) and 557 days (local recurrence group, group B), which included the treatment and follow-up periods. The average duration of response was 149 days for group A-2, and 187 days for group B. A majority of responders (11/19; 58%) were still responsive at the end of the current follow-up. CONCLUSIONS The responses observed may be significant and relatively durable. This study suggests that DC-based cancer vaccines in the future may provide an additional therapy for advanced prostate cancer. Prostate 40:125–129, 1999. © 1999 Wiley-Liss, Inc.
Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma (1997)

We have used comparative genomic hybridization (CGH) to survey genomic regions with aberrant copy numbers of DNA sequences in pancreatic adenocarcinoma. In 12 cell lines and 6 primary tumors from 18 patients with pancreatic adenocarcinomas, highly frequent losses (> 60%) were observed on chromosome arms 6q, 9p, and 18q and the Y chromosome. Moderately frequent losses (40-60%) were observed on chromosome arms 3p, 4q, 8p, and 21q. Interestingly, these samples showed extremely high frequencies of increases in copy numbers of DNA sequences on the long arm of chromosome 20 (15/18, 83%). We further analyzed five cell lines by fluorescence in situ hybridization (FISH) with probes on chromosome 20 to define the increase in copy number more accurately, and we found that 20q was increased to between 5 and 8 copies per cell. These results suggest the existence of an oncogene or oncogenes in 20q that play a role in the development and/or the progression of pancreatic carcinogenesis.
Human Immunodeficiency Virus Type 1 N-Terminal Capsid Mutants That Exhibit Aberrant Core Morphology and Are Blocked in Initiation of Reverse Transcription in Infected Cells (2001)

A group of conserved hydrophobic residues faces the interior of the coiled-coil-like structure within the N-terminal domain of the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA). It has been suggested that these residues are important for maintaining stable structure and functional activity. To investigate this possibility, we constructed two HIV-1 clones, in which Trp23 or Phe40 was changed to Ala. We also constructed a third mutant, D51A, which has a mutation that destroys a salt bridge between Pro1 and Asp51. All three mutants are replication defective but produce virus particles. Mutant virions contain all of the viral proteins, although the amount and stability of CA are decreased and levels of virion-associated integrase are reduced. The mutations do not affect endogenous reverse transcriptase activity; however, the mutants are blocked in their ability to initiate reverse transcription in infected cells and no minus-strand strong-stop DNA is detected. The defect in reverse transcription is associated with striking defects in the morphology of mutant virus cores, as determined by transmission electron microscopy. Our data indicate that the mutations made in this study disrupt CA structure and prevent proper maturation of virus cores. We propose that this results in a defect in core stability or in an early postentry event preceding reverse transcription.
Engineering of a femtomolar affinity binding protein to human serum albumin (2008)

We describe the development of a novel serum albumin binding protein showing an extremely high affinity (K(D)) for HSA in the femtomolar range. Using a naturally occurring 46-residue three-helix bundle albumin binding domain (ABD) of nanomolar affinity for HSA as template, 15 residues were targeted for a combinatorial protein engineering strategy to identify variants showing improved HSA affinities. Sequencing of 55 unique phage display-selected clones showed a strong bias for wild-type residues at nine positions, whereas various changes were observed at other positions, including charge shifts. Additionally, a few non-designed substitutions appeared. On the basis of the sequences of 12 variants showing high overall binding affinities and slow dissociation rate kinetics, a set of seven 'second generation' variants were constructed. One variant denoted ABD035 displaying wild-type-like secondary structure content and excellent thermal denaturation/renaturation properties showed an apparent affinity for HSA in the range of 50-500 fM, corresponding to several orders of magnitude improvement compared with the wild-type domain. The ABD035 variant also showed an improved affinity toward serum albumin from a number of other species, and a capture experiment involving human serum indicated that the selectivity for serum albumin had not been compromised from the affinity engineering.
Alterations of adenylyl cyclase and G proteins in aortocaval shunt-induced heart failure (2004)

Unlike most other experimental models of congestive heart failure, the volume overload model induced by aortocaval shunt (AVS) in rats was found to exhibit enhanced beta-adrenoceptor (beta-AR) signaling. To study whether the adenylyl cyclase (AC)-G protein system is involved in such a change, we examined cardiac AC activity and protein content as well as G(s)alpha and G(i)alpha activities, protein contents, and mRNA levels in both left (LV) and right (RV) ventricles at the failing stage (16 wk after surgery). Basal and forskolin-stimulated AC activities were significantly increased in both LV and RV from the failing hearts; this change was associated with an upregulation of type V/VI AC protein. In contrast to 5'-guanylyl imidodiphosphate and NaF, the stimulatory effect of isoproterenol on AC was increased in the failing heart. Although G(s)alpha and G(i)alpha protein contents in the failing hearts were not altered, the mRNA level for G(s)alpha was decreased by 20% and that for G(i)alpha was increased by 20%. In addition, the activity of G(s)alpha, but not G(i)alpha, as assessed by toxin-catalyzed ADP ribosylation, was significantly decreased in the failing heart. Losartan and imidapril treatments improved cardiac function and attenuated alterations in mRNA levels for G(s)alpha and G(i)alpha proteins, as well as G(s)alpha activity, without affecting changes in AC protein content or activities in heart failure due to volume overload. These data suggest that increased AC activity may contribute to the enhanced beta-AR signaling in the AVS model of heart failure, whereas alterations in gene expression for G proteins may be of an adaptive nature at this stage of heart failure.
Novel imido- and phosphorane-imido-nickel(II) complexes. Crystal and molecular structure of (.mu.3-NH)(.mu.3-NPMe3)(NiClPMe3)3 (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel imido- and phosphorane-imido-nickel(II) complexes. Crystal and molecular structure of (.mu.3-NH)(.mu.3-NPMe3)(NiClPMe3)3Hans Friedrich Klein, Stefan Haller, Herbert Koenig, Michele Dartiguenave, Yves Dartiguenave, and Marie Joelle MenuCite this: J. Am. Chem. Soc. 1991, 113, 12, 4673–4675Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://pubs.acs.org/doi/10.1021/ja00012a042https://doi.org/10.1021/ja00012a042research-articleACS PublicationsRequest reuse permissionsArticle Views183Altmetric-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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Cardiotoxicity of novel HER2-targeted therapies (2013)

Although cardiac toxicity has been reported as an adverse event for novel HER2-targeted therapies, cardiac dysfunction rate of the novel HER2-targeted therapies is significantly lower than the trastuzumab and combination of these agents with trastuzumab did not significantly increase the cardiac adverse events.
Streptococcus mutans biofilm formation: utilization of a gtfB promoter–green fluorescent protein (PgtfB::gfp) construct to monitor development (2002)

The glucosyltransferases of Streptococcus mutans are recognized as important virulence factors for this cariogenic bacterium. To study the expression of the gtfB gene of S. mutans in biofilms, a gtfB promoter (PgtfB)-green fluorescent protein (GFP) reporter system was developed. A Streptococcus-Escherichia coli shuttle vector harbouring a PGTFB::gfp cassette was introduced into S. mutans GS-5, and the expression of GFP by the transformed S. mutans cells was confirmed by fluorescence microscopy. Furthermore, confocal laser scanning microscopy was carried out on biofilms attached to polystyrene plates; enhanced gtfB expression was observed in various microcolonies across these biofilms. To further test the hypothesis that gtfB expression is upregulated in biofilms, flow cytometry analysis was done on planktonic and biofilm cells; this analysis showed an approximately five-fold increase in gtfB expression in the biofilm cells relative to the planktonic cells. Real-time (TaqMan) PCR analysis confirmed that gtfB expression in the biofilm cells was enhanced relative to the planktonic cells. Previously, it has been suggested that the S. mutans gtfC gene might be co-transcribed with gtfB. Therefore, RT-PCR analysis was performed on gtfB-expressing S. mutans; this analysis demonstrated that gtfC was co-transcribed with gtfB. These results indicated that GFP expression can be utilized to examine gene regulation in S. mutans biofilm formation.
Increased Amygdala Responses to Sad But Not Fearful Faces in Major Depression: Relation to Mood State and Pharmacological Treatment (2012)

Aberrant amygdala activation in response to sad facial emotions is specific to the depressed state and is a potential biomarker for a negative affective bias during a depressive episode.
3-[4-(1,2-Diphenylbut-1-enyl)phenyl]acrylic Acid: A Non-Steroidal Estrogen with Functional Selectivity for Bone over Uterus in Rats (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-[4-(1,2-Diphenylbut-1-enyl)phenyl]acrylic Acid: A Non-Steroidal Estrogen with Functional Selectivity for Bone over Uterus in RatsTimothy M. Willson, Brad R. Henke, Tanya M. Momtahen, Paul S. Charifson, Kenneth W. Batchelor, Dennis B. Lubahn, Linda B. Moore, Beverly B. Oliver, Howard R. Sauls, James A. Triantafillou, Steven G. Wolfe, and Philip G. BaerCite this: J. Med. Chem. 1994, 37, 11, 1550–1552Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/jm00037a002https://doi.org/10.1021/jm00037a002research-articleACS PublicationsRequest reuse permissionsArticle Views409Altmetric-Citations124LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts