gebhart/patrepeval huggingface dataset:
Down-regulation by Antisense Oligonucleotides Establishes a Role for the Proline-rich Tyrosine Kinase PYK2 in Angiotensin II-induced Signaling in Vascular Smooth Muscle (2001)

Abnormal vascular smooth muscle cell (VSMC) growth plays a key role in the pathogenesis of hypertension and atherosclerosis. Angiotensin II (Ang II) elicits a hypertrophic growth response characterized by an increase in protein synthesis in the absence of DNA synthesis and cell proliferation. Intracellular signaling mechanisms linking angiotensin type I receptor activation to protein synthesis in VSMC have not been fully characterized. The present study investigates the role of the nonreceptor proline-rich tyrosine kinase 2 (PYK2) in Ang II-induced VSMC protein synthesis and in the regulation of two signaling pathways that have been implicated in the control of protein synthesis, the extracellular signal-regulated kinase (ERK1/2) and the phosphatidylinositol 3-kinase/Akt pathways. PYK2 antisense oligonucleotides were used to down-regulate PYK2 expression in cultured VSMC. An 80% down-regulation in PYK2 expression resulted in an approximately 80% inhibition of ERK1/2 (3.8 +/- 1.3 versus 16.6 +/- 1.8), p70S6 kinase (1.03 +/- 0.03 versus 3.8 +/- 0.5), and Akt activation (3.0 +/- 0.8 versus 16.0 +/- 1.0) by Ang II. Furthermore, PYK2 down-regulation resulted in a complete inhibition of Ang II-induced VSMC protein synthesis. These data conclusively identify PYK2 as an upstream regulator of both the ERK1/2 and the phosphatidylinositol 3-kinase/Akt pathways that are involved in Ang II-induced VSMC protein synthesis.
Excretion patterns of cannabinoid metabolites after last use in a group of chronic users (1985)

The urinary excretion patterns of 86 chronic cannabis users were examined after their last cannabis use by two common screening methods, the semiquantitative EMIT-d.a.u. and the qualitative EMIT-st (Syva Company). We demonstrated that under very strictly supervised abstinence, chronic users can have positive results for cannabinoids in urine at 20 ng/ml or above on the EMIT-d.a.u. assay for as many as 46 consecutive days from admission, and can take as many as 77 days to drop below the cutoff calibrator for 10 consecutive days. For all subjects, the mean excretion time was 27 days. Subject excretion patterns were clearly biphasic, with initial higher rates of excretion not sustained. During the subsequent period of leveling off, most subjects had one or more separate sequences of cannabinoid-negative urine test results, lasting a mean of 3 days each and followed by at least one positive result. Demographic, body type, and drug history variables proved to be only moderate predictors of excretion patterns. Findings were discussed in the context of potential clinical and forensic application.
Benefits Associated with the Interaction of Endophytic Bacteria and Plants (2018)

The endophytic bacteria belong to a larger group of microorganisms that have their life-cycle partly or entirely inside the plant and are located in intra and inter-cellular spaces or in the vascular tissue. These bacteria can be found colonizing aerial parts or roots. This review aims to analyze the colonization strategies of endophytic bacteria through interaction with plants, as well as to highlight the metabolic influence of these organisms in plant tissues, which result in physiological and biochemical changes. Depending on the different mechanisms used internally to colonize a plant, these microorganisms are called obligate, facultative, or passive endophytes. Phytostimulation, biofertilization and biological control are mechanisms that result in the development of the plant through the production of plant hormones, bioavailability of nutrients and antagonistic action to phytopathogens, respectively. The association between endophytic bacteria and plants features important benefits such as significant increases in growth, plant biomass, length of roots, dry matter production, and grain yield. Studies show that there is a great diversity of endophytic bacteria colonizing plant structures that result in several benefits to the host plant.
The Effect of Poloxamer-188 on Neuronal Cell Recovery from Mechanical Injury (2005)

Neuronal injury resulting from mechanical deformation is poorly characterized at the cellular level. The immediate structural consequences of the mechanical loading lead to a variety of inter- and intra-cellular signaling events that interact on multiple time and length scales. Thus, it is often difficult to establish cause-and-effect relationships such that appropriate treatment strategies can be devised. In this report, we showed that treating mechanically injured neuronal cells with an agent that promotes the resealing of disrupted plasma membranes rescues them from death at 24 h post-injury. A new in vitro model was developed to allow uniform mechanical loading conditions with precisely controlled magnitude and onset rate of loading. Injury severity increased monotonically with increasing peak shear stress and was strongly dependent on the rate of loading as assessed with the MTT cell viability assay, 24 h post-injury. Mechanical injury produced an immediate disruption of membrane integrity as indicated by a rapid and transient release of LDH. For the most severe injury, cell viability decreased approximately 40% with mechanical trauma compared to sham controls. Treatment of cells with Poloxamer 188 at 15 min post-injury restored long-term viability to control values. These data establish membrane integrity as a novel therapeutic target in the treatment of neuronal injury.
Overcrowded molecules. I. Substituted 8-tert-butyl-1-(2-pyridyl)naphthalenes, including a thermodynamically stable ketonic tautomer (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOvercrowded molecules. I. Substituted 8-tert-butyl-1-(2-pyridyl)naphthalenes, including a thermodynamically stable ketonic tautomerDonald L. Fields and Thomas H. ReganCite this: J. Org. Chem. 1971, 36, 20, 2986–2990Publication Date (Print):October 1, 1971Publication History Published online1 May 2002Published inissue 1 October 1971https://pubs.acs.org/doi/10.1021/jo00819a017https://doi.org/10.1021/jo00819a017research-articleACS PublicationsRequest reuse permissionsArticle Views55Altmetric-Citations11LEARN 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
The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed (1994)

In a previous study of a t(4;16)(q26;p13) translocation, found in a human malignant T-cell lymphoma the BCMA gene, located on chromosome band 16p13.1, has been characterized. In this study we show that the BCMA gene is organized into three exons and its major initiation transcription site is located 69 nucleotides downstream of a TATA box. RNase protection assays demonstrated that the BCMA gene is preferentially expressed in mature B cells, suggesting a role for this gene in the B-cell developmental process. A cDNA complementary to the BCMA cDNA was cloned and sequenced and its presence was assessed by RNase protection assay and anchor-PCR amplification. This antisense-BCMA RNA is transcribed from the same locus as BCMA, and exhibits mRNA characteristic features, e.g. polyadenylation and splicing. It also contains an ORF encoding a putative 115 aa polypeptide, presenting no homology with already known sequences. RNase protection assays demonstrated the simultaneous expression of natural sense and antisense-BCMA transcripts in the majority of human B-cell lines tested.
[Formulation and clinical test of a novel mucosal adhesive ointment]. (1983)

A novel mucosal adhesive ointment on the base of partly neutralized polymethacrylic acid methyl ester (Eudispert) was formulated. The flow curves of the ointment show a pseudoplastic quality without any thixotropic effect. The viscosity depended on the kind and concentration of the base. During the clinical studies the pure ointment as well as a tretinoin-preparation for a lichen planus treatment showed no local irritation, good mucosal adhesion and suitable way of application for the patients.
The yeast activator HAP1--a GAL4 family member--binds DNA in a directly repeated orientation. (1994)

The yeast transcriptional activator HAP1 contains a DNA-binding domain homologous to GAL4, PPR1, and related factors. By selecting random HAP1-binding sites, we found that HAP1, like GAL4, binds to two CGG triplets. Unlike GAL4, the CGGs in the HAP1 consensus are in a direct and not inverted orientation. Sites with inverted CGGs were not recovered, and mutations converting the direct repeat of CGGs to an inverted repeat greatly reduce HAP1-binding affinity. Also, the 6-bp spacer between the CGGs contains a consensus TA that is positioned asymmetrically. Dimethylsulfate protection patterns on six of these sites show protections and enhancements that also lie in a directly repeated orientation, suggesting that the two HAP1 DNA recognition domains of a HAP1 homodimer are oriented in a directly repeated configuration on the DNA. Moreover, substitution of the HAP1 dimerization domain with that of PPR1, which forms coiled-coils and dimerizes symmetrically, did not diminish the ability of the protein to bind selectively to a direct repeat. This result suggests that one DNA-binding domain of the HAP1 homodimer must be able to swivel 180 degrees relative to the dimerization domain to make specific contacts with the second CGG triplet. Our results present a novel example of domain swiveling in one of the two identical subunits of a homodimer to accommodate specific DNA contacts to both CGG triplets of a direct repeat.
Infectious entry pathway of adenovirus type 2 (1991)

Internalization of the infectious fraction of human adenovirus type 2 into HeLa cells was followed by a quantitative internalization assay. Treatments known to selectively block receptor-mediated endocytosis reduced the internalization of infectious virus to an extent close to the reduction of endocytosis of transferrin. This suggests that one of the first steps in the infectious cycle of adenovirus type 2 is internalization by the coated-pit and -vesicle pathway.
Calcific Periarthritis as the Only Clinical Manifestation of Hypophosphatasia in Middle-Aged Sisters (2013)

Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate and inhibitor of mineralization, leads frequently to premature tooth loss and often to rickets or osteomalacia. In affected adults, the excess PPi sometimes also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy, or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in ligaments or around joints when the condition is called calcific periarthritis (CP). We report three middle-aged sisters with CP as the only clinical manifestation of HPP. Each presented during early adult life with recurrent episodes of pain principally around the shoulders, elbows, wrists, hips, or Achilles tendon. Otherwise, they were in good health, including no history of unusual dental disease, fractures, or pseudofractures. Calcific deposits were identified in symptomatic areas principally by ultrasonographic assessment but also confirmed radiographically. All three sisters had low serum levels of total and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of the TNSALP substrate pyridoxal 5'-phosphate together characteristic of HPP. Mutation analysis revealed that each carried a single unique 18-bp duplication within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons and their mother, who was without signs of CPPD deposition or CP but had knee osteoarthritis. We find that CP can be the only complication of HPP in adults. Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a useful sign of HPP, especially when the CP is familial.
Control of melanocyte differentiation by a MITF–PDE4D3 homeostatic circuit (2010)

Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a variety of biological processes. The magnitude and duration of cAMP expression are regulated by both production and hydrolysis. Melanocyte-stimulating hormone (MSH) plays a crucial role in pigment cell differentiation via cAMP-regulated expression of the master transcription factor MITF. We report the identification of phosphodiesterase 4D3 as a direct target of the MSH/cAMP/MITF pathway. This creates a negative feedback loop that induces refractoriness to chronic stimulation of the cAMP pathway in melanocytes. This homeostatic pathway highlights a potent mechanism controlling melanocyte differentiation that may be amenable to pharmacologic manipulation for skin cancer prevention.
Enhancement of the biological activity of BMP‐2 by synthetic dextran derivatives (2008)

In the present study, we explored the binding capacity of synthetic heparin-like dextran derivatives to recombinant human bone morphogenetic protein 2 (BMP-2), a heparin-binding osteoinductive growth factor. Affinity electrophoresis analysis provided evidence that carboxymethylated dextran polymers grafted with high amounts of benzylamide groups (named DMCB) interact with BMP-2. The capability of such polysaccharides to potentiate the growth factor biological activity was then investigated. In vitro, DMCB dose-dependently promoted osteoblast differentiation induced by BMP-2 in C2C12 myoblasts more efficiently than heparin. A screening study provided evidence that the potentiating effects of the dextran derivatives on the BMP-2-induced alkaline phosphatase activity improved with their benzylamide groups content and, therefore, with their affinity for the growth factor. The biological activity of BMP-2 was monitored in the culture medium after 6 days using C2C12 cells (containing a BMP sensitive luciferase reporter gene). Like heparin, DMCB sustained the biological activity of the growth factor; this result suggests that the formation of the BMP-2/DMCB complex may protect the protein from being inactivated. In rats in vivo, DMCB also stimulated ectopic calcification mediated by BMP-2. These data indicate that dextran-based polysaccharides prolong the half-life of the growth factor and promote its biological activity.
Sumatriptan and cerebral perfusion in healthy volunteers. (1992)

1. The effect of sumatriptan on regional cerebral perfusion was studied in healthy volunteers. 2. Intravenous sumatriptan (2 mg) had no detectable effect on regional cerebral perfusion as measured using a SPECT system with 99technetiumm labelled hexemethylpropyleneamineoxime. 3. Sumatriptan had no effect on pulse, blood pressure or ECG indices. 4. All six volunteers experienced minor adverse effects during the intravenous infusion.
Influence of AT 1 Receptor Blockade on Blood Pressure, Renal Haemodynamics and Hormonal Responses to Intravenous Angiotensin II Infusion in Hypertensive Patients (2002)

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean +/- SEM, 106 +/- 2 mmHg) was significantly decreased compared with treatment with losartan (110 +/- 2 mmHg) and valsartan (109 +/- 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 +/- 0.4%) significantly more than losartan (1.5 +/- 0.4%) and valsartan (1.6 +/- 0.4%) and reduced the increase in aldosterone secretion (17 +/- 5 pg/ml/) significantly more than losartan (74 +/- 17 pg/ml/) and valsartan (82 +/- 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT1 receptor blockade with candesartan.
The attraction of chemokines as a target for specific anti‐inflammatory therapy (2006)

Since the identification of the first chemotactic cytokines 20 years ago, the field has mushroomed, with the discovery of approximately 40 ligands, which interact with 20 different cell surface receptors. At the time of writing this review, a PubMed trawl using the word 'chemokine' will recover over 28,000 manuscripts. In this article, we will give a short history of the discovery of chemokines and provide examples of the potential for therapeutic targeting of the chemokine network in inflammatory disease.
Hypocholesterolemic effect of Lactobacillus gasseri SBT0270 in rats fed a cholesterol-enriched diet (2001)

The effects of administration of Lactobacillus gasseri SBT0270 on serum lipids and bile acids, faecal bile acids and microflora were estimated in hypercholesterolemic rats. An effective dose of strain SBT0270 to exert its hypocholesterolemic effect was 10(9) viable cells/d. The dose of 10(9) cells/d did not affect the faecal coliform counts, but the number of faecal lactobacilli in rats fed this dose was significantly higher than that in the control group observed at the end of feeding period. Hypocholesterolemic effect of Lb. gasseri SBT0270 was attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation and to enhance the excretion of acidic steroids in faeces of hypercholesterolemic rats.
Active Notebook: A Personal and Group Productivity Tool for Managing Information (1995)

This paper describes Active Notebook, a collection of software tools which work together to allow individuals to label document-based information with conceptual classifications, and organize these documents into a semantic taxonomy for later browsing and retrieval. Tools are also provided to support sharing documents and references with peers. Novel techniques for taxonomy sharing avoid the need for a single, global taxonomy to which everyone adheres. Ongoing work on active reminding is described. 1 Introduction More and more, we find ourselves in the information management business. This is especially true for people working on research, but it is apparent from reading popular press in other fields that the problem is pervasive. The number of commercial software tools for organizing and retrieving information is growing at a rapid pace. We introduce Active Notebook, another tool in this category, which takes as its goal to make it easy for users to gain high level semantic control ...
Large metal ion-centered template reactions. Chemical and spectral studies of the "superphthalocyanine" dioxocyclopentakis(1-iminoisoindolinato)uranium(VI) and its derivatives (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLarge metal ion-centered template reactions. Chemical and spectral studies of the "superphthalocyanine" dioxocyclopentakis(1-iminoisoindolinato)uranium(VI) and its derivativesTobin J. Marks and Djordje R. StojakovicCite this: J. Am. Chem. Soc. 1978, 100, 6, 1695–1705Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://pubs.acs.org/doi/10.1021/ja00474a009https://doi.org/10.1021/ja00474a009research-articleACS PublicationsRequest reuse permissionsArticle Views701Altmetric-Citations107LEARN 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
Effect of clindamycin, erythromycin, lincomycin, and tetracycline on growth and extracellular lipase production by propionibacteria in vitro (1982)

Two propionibacteria identified as Propionibacterium acnes and Propionibacterium granulosum were grown anaerobically in the presence of growth subinhibitory concentrations (0.25 and 0.5 minimal inhibitory concentrations) of clindamycin, erythromycin, lincomycin, and tetracycline. Viable counts and assays of extracellular lipase were performed on samples taken at 24-h intervals over a 96-h period. The results showed that lincomycin and clindamycin could inhibit the production of the enzyme by both strains with little effect on their growth rates. Tetracycline caused inhibition of lipase production by P. granulosum only. Although production of the enzyme by P. acnes was delayed in the presence of tetracycline, the final titer was the same as the control. Erythromycin had little effect on growth and enzyme production of either strain. It is possible, therefore, that certain antibiotics used in acne therapy may act not only as bactericidal agents but also as inhibitors of enzyme production under non-growth-limiting conditions.