gebhart/patrepeval huggingface dataset:
Genetic approaches identify adult pituitary stem cells (2008)

Adult tissues undergo continuous cell turnover in response to stress, damage, or physiological demand. New differentiated cells are generated from dedicated or facultative stem cells or from self-renewing differentiated cells. Here we describe a different stem cell strategy for tissue maintenance, distinct from that observed for dedicated or facultative stem cells. We report the presence of nestin-expressing adult stem cells in the perilumenal region of the mature anterior pituitary and, using genetic inducible fate mapping, demonstrate that they serve to generate subsets of all six terminally differentiated endocrine cell types of the pituitary gland. These stem cells, while not playing a significant role in organogenesis, undergo postnatal expansion and start producing differentiated progeny, which colonize the organ that initially entirely consisted of differentiated cells derived from embryonic precursors. This generates a mosaic organ with two phenotypically similar subsets of endocrine cells that have different origins and different life histories. These parallel but distinct lineages of differentiated cells in the gland may help the maturing organism adapt to changes in the metabolic regulatory landscape.
Extended confocal microscopy of myocardial laminae and collagen network (1998)

Ventricular myocardium has a complex three-dimensional structure which has previously been inferred from two-dimensional images. We describe a technique for imaging the 3D organization of myocytes in conjunction with the collagen network in extended blocks of myocardium. Rat hearts were fixed with Bouin's solution and perfusion-stained with picrosirius red. Transmural blocks from the left ventricular free wall were embedded in Agar 100 resin and mounted securely in an ultramicrotome chuck. Confocal fluorescence laser scanning microscopy was used to obtain 3D images to a depth of 60 microns in a contiguous mosaic across the surface. Approximately 50 microns was then cut off the surface of the block with an ultramicrotome. This sequence was repeated 20 times. Images were assembled and registered in 3D to form an extended volume 3800 x 800 x 800 microns 3 spanning the heart wall from epicardium to endocardium. Examples are given of how digital reslicing and volume rendering methods can be applied to the resulting dataset to provide quantitative structural information about the 3D organization of myocytes, extracellular collagen matrix and blood vessel network of the heart.
Hydrophobic, Highly Conductive Ambient-Temperature Molten Salts (1996)

New, hydrophobic ionic liquids with low melting points (<-30 degrees C to ambient temperature) have been synthesized and investigated, based on 1,3-dialkyl imidazolium cations and hydrophobic anions. Other imidazolium molten salts with hydrophilic anions and thus water-soluble are also described. The molten salts were characterized by NMR and elemental analysis. Their density, melting point, viscosity, conductivity, refractive index, electrochemical window, thermal stability, and miscibility with water and organic solvents were determined. The influence of the alkyl substituents in 1, 2, 3, and 4(5)-positions on these properties was scrutinized. Viscosities as low as 35 cP (for 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)amide (bis(triflyl)amide) and trifluoroacetate) and conductivities as high as 9.6 mS/cm were obtained. Photophysical probe studies were carried out to establish more precisely the solvent properties of 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)amide). The hydrophobic molten salts are promising solvents for electrochemical, photovoltaic, and synthetic applications.
Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection. (1993)

13 patients with human immunodeficiency virus type 1 infection class II-IV, but without opportunistic infection or neoplasm, received 6 micrograms (3.6 x 10(4) IU) of polyethylene glycol recombinant human interleukin 2 (PEG IL-2) intradermally twice a week for 4 mo were then followed for an additional 6 mo. Clinical, immunological, and viral parameters were monitored in the patients, all of whom were taking zidovudine. The cutaneous administration of PEG IL-2 resulted in an indurated zone resembling a delayed-type hypersensitivity response of 26 +/- 1 mm diameter (676 mm2) at 72-96 h after injection throughout the 4 mo of administration. This dose, which was appreciably lower than in most previous trials, was not associated with local or systemic toxicity. No increase in the viral burden of circulating leukocytes or plasma occurred. A number of immunological functions were stimulated by this course of therapy. All patients demonstrated high levels of lymphokine-activated killer cell activity by cells freshly removed from the circulation and in the absence of in vitro exposure to IL-2. Natural killer cell activity was also enhanced. Limiting dilution analysis revealed an increase in the frequency of IL-2-responsive cells from abnormally low to levels above normal during the course of injections. In a subgroup of four patients with > or = 400 CD4+ T cells/microliter at entry, there was a trend to sustained increases in CD4+ T cell numbers. However, this increase did not reach statistical significance. This subset of patients also exhibited higher proliferative responses to phytohemagglutinin as mitogen. Several of these effects persisted for 3-6 mo after cessation of therapy. In conclusion, low-dose IL-2 regimens lead to sustained immune enhancement in the absence of toxicity. We suggest pursuit of this approach for further clinical trials both as prophylaxis and therapy.
Synthesis and Evaluation of Anticonvulsant and Antimicrobial Activities of 3‐Hydroxy‐6‐methyl‐2‐substituted 4H‐Pyran‐4‐one Derivatives (2004)

In this study, thirteen 3-hydroxy-6-methyl-2-substituted 4H-pyran-4-one derivatives were synthesized for the evaluation of their potential anticonvulsant activity. Mannich bases were prepared by the reaction of substituted piperazine derivatives with allomaltol and formaline. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR and elemental analysis. Their anticonvulsant activities were determined in vivo by maximal electroshock (MES), sub-cutaneous Metrazol (scMet), and rotorod toxicity tests for neurological deficits. The antimicrobial activities of the synthesized compounds were investigated in vitro against some bacteria and fungi using the microdilution broth method. Ac-cording to the activity studies, 3-hydroxy-6-methyl-2-[4-(2-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-4H-pyran-4-one (3i) was the compound determined to be most active in the scMet test for all doses at four hours and for the 300 mg/kg dose at half an hour. 2-[4-(4-Chloro-phenyl)-piperazin-1-ylmethyl]-3-hydroxy-6-methyl-4H-pyran-4-one (3f) was found to be protective against MES whereas 2-chlorophenyl derivative (3e) was not. Looking at the antifungal activity results, compounds 3b, 3h, and 3i were determined to have activity against all fungi.
Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. (1991)

The regulation of type 1 plasminogen activator inhibitor (PAI-1) gene expression was studied in vivo employing a murine model system. Nuclease protection analysis revealed relatively high concentrations of PAI-1 mRNA in the aorta, adipose tissue, heart, and lungs of untreated CB6 (BalbC X C57B16) mice. Treatment of CB6 mice with LPS, TNF-alpha, or transforming growth factor-beta (TGF-beta) increased the steady-state levels of PAI-1 mRNA within 3 h in all tissues examined. However, the greatest responses to TGF-beta were observed in adipose tissue and the kidney, while LPS and TNF-alpha strongly stimulated PAI-1 gene expression in the liver, kidney, lung, and adrenals. In C3H/HeJ mice, which exhibit defective TNF-alpha release in response to LPS, the response of the PAI-1 gene to LPS was severely attenuated. However, injection of these mice with TNF-alpha increased PAI-1 mRNA in a tissue-specific pattern strikingly similar to that observed in LPS-treated CB6 mice. These results demonstrate that the PAI-1 gene is regulated in a complex and tissue-specific manner in vivo, and suggest a role for TNF-alpha in the response of the PAI-1 gene to sepsis.
P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation (1999)

P-selectin is a leukocyte adhesion receptor present in endothelial cells and platelets. We examined the role of P-selectin in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis using P-selectin-deficient mice and chimeric mice expressing P-selectin only in platelets or endothelial cells. P-selectin-deficient mice exhibited more severe glomerular damage with increased interstitial mononuclear leukocytic infiltrates, and had significantly increased proteinuria and mortality when compared to wild-type mice. P-selectin on the endothelium was predominantly responsible for protection from the exacerbated disease, because chimeric mice with endothelial P-selectin, and not mice with platelet P-selectin, showed glomerular injury similar to that in wild-type animals. Levels of soluble circulating P-selectin were increased in nephritic wild-type mice and in chimeric mice with endothelial P-selectin, but not platelet P-selectin. Levels of soluble P-selectin, which has been shown to be anti-inflammatory in vitro, were inversely associated with the severity of disease. P-selectin was not expressed in the endothelium of the glomerulus or interstitium. Thus, the protective effect in wild-type mice may be accounted for, in part by soluble P-selectin shed by non-renal endothelial cells, although other endothelial P-selectin-dependent mechanisms cannot be ruled out.
Fatty Acid Composition of Indica‐and Japonica‐Types of Rice Bran and Milled Rice (1989)

Abstract Fatty acid compositions of 10 cultivars each of Indicaand Japonica types of rice bran and milled rice were investigated. The Indica‐type, as compared with the Japonica‐type, had significantly higher palmitic, stearic, linolenic, and arachidic acid contents and lower linoleic and eicosenoic acid contents in the bran and milled rice, and lower oleic acid content in the bran. The correlation coefficient between oleic and linoleic acid contents of bran and milled rice was negative in the Indica‐and Japonica‐types and was the highest between all fatty acids. The regression line in the scatter diagrams between oleic and linoleic acid contents of bran and milled rice divided the Indica and Japonica lines.
Glomerular Hyperfiltration With Hyperglycemia in the Spontaneously Diabetic Torii (SDT) Fatty Rat, an Obese Type 2 Diabetic Model (2021)

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.
Phenotypic diversity in hypertrophic cardiomyopathy (2002)

In recent years, the main focus of human genetic studies on hypertrophic cardiomyopathy (HCM) switched from discovering novel genes and defining disease-causing mutations to studies of mutation distribution in disease populations. Eventually these studies will define genotype-phenotype relationships, which may provide clues to understanding the disease process and help to select the most appropriate treatment strategy. Animal models engineered to recapitulate human disease provide a unique tool to investigate the pathogenic mechanisms and evaluate potential therapies. In this review, we present the spectrum of clinical HCM in the context of the genetic heterogeneity of this common human disease. Recent progress made in understanding molecular pathways that result in cardiac hypertrophy and the factors that modify these processes are discussed.
Construction of a bifunctional mRNA in the mouse by using the internal ribosomal entry site of the encephalomyocarditis virus. (1992)

Picornaviral mRNAs have been shown to possess special structures in their 5' nontranslated regions (5'NTRs) that provide sites for internal binding of ribosomes and thus direct cap-independent translation. The translational cis-acting elements for ribosomal internal entry into the 5'NTR of encephalomyocarditis virus (EMCV), a member of family Picornaviridae, have been named the internal ribosomal entry site (IRES). All of the published experiments regarding the IRES function of the picornavirus 5'NTR, however, were performed with cell extracts in vitro or with tissue culture cells in transient assay systems. In this study, we examined the IRES function of the EMCV 5'NTR in chimeric mouse embryos and demonstrated that this element does in fact work stably in mouse embryos as well as in embryonic stem (ES) cells. By using a dicistronic vector, pWH8, consisting of a promoter-driven neomycin resistance gene (neo) followed by the EMCV 5'NTR-lacZ sequence, we showed that more than half of the ES cells made G418 resistant by the vector stained positive for beta-galactosidase (beta-gal). On Northern (RNA) blots, all of the clones analyzed revealed a transcript of the expected size containing both the beta-gal and the neo cistrons. These results indicate that dicistronic mRNAs are produced from the stably integrated vector in those ES clones and that both of the cistrons are translated to produce functional proteins. The chimeric embryos derived from these ES clones also stained positive for beta-gal, suggesting that the bifunctional mRNAs are active in the embryos. This dicistronic vector system provides a novel tool by which to obtain temporally and spatially coordinated expression of two different genes driven by a single promoter in a single cell in mice.
Methylene-Bridged P-Chiral Diphosphines in Highly Enantioselective Reactions (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTMethylene-Bridged P-Chiral Diphosphines in Highly Enantioselective ReactionsYoshinori Yamanoi and Tsuneo ImamotoView Author Information Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Cite this: J. Org. Chem. 1999, 64, 9, 2988–2989Publication Date (Web):April 10, 1999Publication History Received26 January 1999Published online10 April 1999Published inissue 1 April 1999https://pubs.acs.org/doi/10.1021/jo990131mhttps://doi.org/10.1021/jo990131mrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1989Altmetric-Citations239LEARN 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 (2)»Supporting Information Supporting Information SUBJECTS:Alkyls,Ketones,Ligands,Organophosphorus compounds,Stereoselectivity Get e-Alerts
Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products (2010)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAtroposelective Total Synthesis of Axially Chiral Biaryl Natural ProductsGerhard Bringmann*, Tanja Gulder†‡, Tobias A. M. Gulder†§, and Matthias Breuning*View Author Information Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany* To whom correspondence should be addressed. E-mail: [email protected]; [email protected]†These authors contributed equally to this work.‡Present address: Institute of Organic Chemistry, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany.§Present address: Kekulé Institute of Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk Str. 1, 53121 Bonn, Germany.Cite this: Chem. Rev. 2011, 111, 2, 563–639Publication Date (Web):October 12, 2010Publication History Received20 May 2010Published online12 October 2010Published inissue 9 February 2011https://pubs.acs.org/doi/10.1021/cr100155ehttps://doi.org/10.1021/cr100155ereview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views21715Altmetric-Citations1104LEARN 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:Aromatic compounds,Hydrocarbons,Lactones,Organic compounds,Pharmaceuticals Get e-Alerts
Targeting Vault Nanoparticles to Specific Cell Surface Receptors (2008)

As a naturally occurring nanocapsule abundantly expressed in nearly all-eukaryotic cells, the barrel-shaped vault particle is perhaps an ideal structure to engineer for targeting to specific cell types. Recombinant vault particles self-assemble from 96 copies of the major vault protein (MVP), have dimensions of 72.5 x 41 nm, and have a hollow interior large enough to encapsulate hundreds of proteins. In this study, three different tags were engineered onto the C-terminus of MVP: an 11 amino acid epitope tag, a 33 amino acid IgG-binding peptide, and the 55 amino acid epidermal growth factor (EGF). These modified vaults were produced using a baculovirus expression system. Our studies demonstrate that recombinant vaults assembled from MVPs containing C-terminal peptide extensions display these tags at the top and bottom of the vault on the outside of the particle and can be used to specifically bind the modified vaults to epithelial cancer cells (A431) via the epidermal growth factor receptor (EGFR), either directly (EGF modified vaults) or as mediated by a monoclonal antibody (anti-EGFR) bound to recombinant vaults containing the IgG-binding peptide. The ability to target vaults to specific cells represents an essential advance toward using recombinant vaults as delivery vehicles.
Structure-Based Optimization of a Non-β-lactam Lead Results in Inhibitors That Do Not Up-Regulate β-Lactamase Expression in Cell Culture (2005)

Bacterial expression of beta-lactamases is the most widespread resistance mechanism to beta-lactam antibiotics, such as penicillins and cephalosporins. There is a pressing need for novel, non-beta-lactam inhibitors of these enzymes. One previously discovered novel inhibitor of the beta-lactamase AmpC, compound 1, has several favorable properties: it is chemically dissimilar to beta-lactams and is a noncovalent, competitive inhibitor of the enzyme. However, at 26 microM its activity is modest. Using the X-ray structure of the AmpC/1 complex as a template, 14 analogues were designed and synthesized. The most active of these, compound 10, had a K(i) of 1 microM, 26-fold better than the lead. To understand the origins of this improved activity, the structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 A, respectively. Compound 10 was active in cell culture, reversing resistance to the third generation cephalosporin ceftazidime in bacterial pathogens expressing AmpC. In contrast to beta-lactam-based inhibitors clavulanate and cefoxitin, compound 10 did not up-regulate beta-lactamase expression in cell culture but simply inhibited the enzyme expressed by the resistant bacteria. Its escape from this resistance mechanism derives from its dissimilarity to beta-lactam antibiotics.
Thrombospondin measured in whole blood???an indicator of platelet activation (1996)

Abnormal platelet activation may be involved in prethrombotic states and lead to thromboembolism. When platelets become activated, they release thrombospondin (TSP) from their alpha-granules which binds mainly to the surface of activated platelets, platelet-derived microparticles and other blood cells. To determine bound as well as free TSP in a single assay, we developed an indirect ELISA to measure TSP in fixed whole blood. The intra-assay variance was less than 5% and 97% of purified standard TSP, added to whole blood samples, was recovered with the ELISA. Blood collected with a 20G needle into a syringe resulted in lower "whole blood TSP' values than blood collected with the Vacutainer system. Whole blood TSP levels were measured in 66 healthy blood donors (20F, 46M) aged 25-75 years. The mean whole blood TSP concentration was 33 +/- 19 ng/ml. No significant difference in whole blood TSP was found between healthy females and males (35 +/- 23 ng/ml vs. 33 +/- 17 ng/ml).