gebhart/patrepeval huggingface dataset:
Enantiospecific Synthesis of the Bridged Pyrrolizidine Core of Asparagamine A: Dipolar Cycloadditions of Azomethine Ylides Derived from the Sulfonylation of Vinylogous Amides. (2002)

An important precursor to the bridged pyrrolizidine core 2 of asparagamine A is vinylogous amide 1. The key reaction in the synthesis of 2 is an intramolecular 1,3-dipolar cycloaddition of an azomethine ylide derived from the sulfonylation of 1. A variety of highly functionalized pyrrolidines, pyrrolizidines, and indolizidines can be prepared from vinylogous amides such as 1. Tf=trifluoromethanesulfonyl. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Retinoic acid-induced duplication of the zebrafish retina. (1992)

Exogenous treatment of zebrafish embryos with retinoic acid induces a duplication of the retinas during development. These effects occur only when retinoic acid is applied within a 2-hr period prior to and during the initial formation of the optic primordia, and they are concentration-dependent. Light microscopic examination reveals that the second retina derives from cells in the ventral region of the developing eyecup that normally become pigment epithelial cells. Two distinct ganglion cell fields are usually observed in eyes with duplicated retinas. Bundles of axons from each ganglion cell field join as they leave the eye and innervate the contralateral tectum.
Clinical implications of benign multiple sclerosis: A 20‐year population‐based follow‐up study (2004)

Abstract In 2001, we followed up all patients from the 1991 Olmsted County Multiple Sclerosis (MS) prevalence cohort. We found that the longer the duration of MS and the lower the disability, the more likely a patient is to remain stable and not progress. This is particularly powerful for patients with benign MS with Expanded Disability Status Scale score of 2 or lower for 10 years or longer who have a greater than 90% chance of remaining stable. This is important because these patients represent 17% of the entire prevalence cohort. These data should assist in the shared therapeutic decision‐making process of whether to start immunomodulatory medications. Ann Neurol 2004;56:303–306
Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. (1994)

The aquaporins transport water through membranes of numerous tissues, but the molecular mechanisms for sensing changes in extracellular osmolality and regulating water balance in brain are unknown. We have isolated a brain aquaporin by homology cloning. Like aquaporin 1 (AQP1, also known as CHIP, channel-forming integral membrane protein of 28 kDa), the deduced polypeptide has six putative transmembrane domains but lacks cysteines at the known mercury-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl2, even after substitution of cysteine at the predicted mercury-sensitive site. Northern analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicates this fourth mammalian member of the aquaporin water channel family (designated gene symbol, AQP4) as the osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
Synthesis of O‐Glycopeptides of the Tumor‐Associated TN‐ and T‐Antigen Type and Their Binding to Bovine Serum Albumin (1986)

The synthesis of immunologically relevant conjugates from bovine serum albumin (BSA) and glycotripeptides with T N ‐ and T‐antigen structures has been achieved for the first time. In the glycoserylserylthreonines, two monosacharide (T N ) and two disaccharide (T) units are α‐glycosidically linked with serine and threonine; they correspond to the N ‐terminal structural elements of glycophorin A with M blood group characteristics. The synthesis is accomplished by means of a special protecting group technique (Sacch = mono‐ or disaccharide unit). equation image
Substitutions at the Thiazole Moiety of Epothilone (1998)

Epothilone A is metalated at low temperature with an excess of butyllithium preferentially at C19 of the thiazole moiety.After addition of various carbon and heteroatom electrophiles the correspondmg substitution products were obtained.Some of them have similar cytotoxic activity than the starting material.Epothilones are currently of great interest due to their potential as anticancer agents.'.2In previous papers we reported various derivatizations of the macrocycle and of the adjacent double bond of epothilones?Modification of the thiazole moiety of epothilone A (1) via a selective deprotonation-electrophile addition sequence should easily access a variety of analogs to study structure activity relationships, although it was difficult to predict whether strong nucleophilic bases like BuLi deprotonate the thiazole group regioselectively (Scheme 1). Scheme 1 Possible reaction sites of epothilone A (I) with nucleophilic bases. deprotonation deprotonation addition dThus in a first experiment, epothilone A (1) was treated with 5 equivalents of B S i in THF at -90 OC.The solution soon turned orange and after 15 minutes acetic acid-& was added.TLC of the pale yellow reaction mixture showed just starting material and two minor spots.After usual workup and chromatographic separation three fractions were obtained in 70, 10 and 5% yields.
Evaluation of toxicity profile of leaf base extract of Sorghum bicolor in rat. (2009)

The toxicity profile of 70% methanolic extract of Sorghum bicolor leaf base widely used in ethnomedicine was evaluated in male rats treated daily for 28 days using 100 – 400 mg/kg p. o. doses. No adverse clinical signs were observed. There was no significant change in the feed intake, body weight and relative organ weight except the significant (P and differential white blood cells), hepatic function indices (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, direct bilirubin, total bilirubin, alkaline phosphatase, albumin, total protein) as well as renal function indices (urea and creatinine). Uric acid was however reduced significantly (P
Cell-Based Gene Transfer of Vascular Endothelial Growth Factor Attenuates Monocrotaline-Induced Pulmonary Hypertension (2001)

These results indicate that cell-based VEGF gene transfer is an effective method of preventing the development and progression of pulmonary hypertension in the monocrotaline model and suggest a potential therapeutic role for angiogenic factors in the therapy of this devastating disease.
RADIOIMMUNOASSAY OF METHIONINE‐AND LEUCINE‐ENKEPHALINS IN REGIONS OF RAT BRAIN AND COMPARISON WITH ENDORPHINS ESTIMATED BY A RADIORECEPTOR ASSAY (1978)

Abstract— Radioimmunoassays (RIAs) selective for methionine‐enkephalin (Met‐ENK) and leucineenkephalin (Leu‐ENK) have been developed using competition towards binding of 10 pM 125 I‐enkephalins to antibodies raised in rabbits against ENKs coupled to ovalbumin with carbodiimide. The high sensitivity of the RIAs (IC 50 0.57 n m and 0.55 n m for Met‐ and Leu‐ENK, respectively) allowed estimation of the enkephalin content in extracts of all rat brain regions. Regional levels are compared with those determined on the same extracts by a radioreceptor assay (RRA) using competition towards binding of 5 n m [ 3 H]Leu‐ENK to rat striatal membranes. Optimal conditions for killing the animals and extracting the endorphins have been carefully investigated: killing by rapid microwave irradiation was not found necessary as long as brain regions were homogenized into 0.1 n ‐HCl before deproteinization. Marked differences both in total endorphins (RRA) and ENKs (RIA) between regions are observed with similar ranking of the various regions: highest levels are found in striatum and hypothalamus and lowest in cerebellum and hippocampus. In each region the total ENK levels (RIA) represent only 2–13% of the total endorphins (RRA) suggesting the presence of large amounts of endorphins other than the ENKs.
Regulation by lipids of cofactor binding to a peripheral membrane enzyme: binding of thiamin pyrophosphate to pyruvate oxidase (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegulation by lipids of cofactor binding to a peripheral membrane enzyme: binding of thiamin pyrophosphate to pyruvate oxidaseThomas A. O'Brien, Robert Blake, II, and Robert B. GennisCite this: Biochemistry 1977, 16, 14, 3105–3109Publication Date (Print):July 12, 1977Publication History Published online1 May 2002Published inissue 12 July 1977https://pubs.acs.org/doi/10.1021/bi00633a010https://doi.org/10.1021/bi00633a010research-articleACS PublicationsRequest reuse permissionsArticle Views65Altmetric-Citations25LEARN 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
A Role for Malonyl-CoA in Glucose-Stimulated Insulin Secretion from Clonal Pancreatic β-Cells (1989)

To gain insight into the relationship between acyl coenzyme A (CoA) esters and glucose-induced insulin release, acyl-CoA profiles were determined in clonal pancreatic beta-cells (HIT). A high sensitivity high performance liquid chromatography method was used to measure malonyl, succinyl, beta-hydroxy beta-methylglutaryl and acetyl-CoA esters and free CoASH. Malonyl-CoA content increased more than 3-fold following exposure of HIT cells to 10 mM glucose. The rise in malonyl-CoA, which preceded insulin secretion, was evident 2 min after exposure to glucose and was sustained for at least 30 min. The increase in malonyl-CoA was associated with inhibition of fatty acid oxidation, increased de novo lipid synthesis and a rise in diacylglycerol content. Succinyl-CoA levels, which may reflect anaplerotic influx into the citric acid cycle, were elevated in the presence of glucose. The concentration of acetyl-CoA and the ratio of free CoASH to acetyl-CoA was unchanged. The data are consistent with a metabolic model in which malonyl-CoA mediates the switch from fatty acid catabolism to lipid synthesis during glucose stimulation of beta-cells. We suggest that these changes in lipid metabolism, by leading to increased diacylglycerol synthesis or protein acylation could play a pivotal role in the regulation of the sustained phase of insulin secretion.
Characterization of the 5′-Flanking Region and Regulation of Transcription of Human BAFF-R Gene (2009)

B-cell activating factor (BAFF) is critical for maintaining the development and homeostasis of B cells. Overexpression of BAFF is associated with autoimmune diseases and malignant B lymphoma. BAFF receptor (BAFF-R) was found to be a specific receptor of BAFF. It not only plays a significant role in splenic B-cell maturation but also works as a major mediator in BAFF-dependent costimulatory response in peripheral B and T cells. Previous studies have demonstrated that BAFF-R is related to several diseases; however, the molecular mechanism of BAFF-R genic transcription has not been clearly defined. The aim of this study was to investigate the transcriptional regulation of the BAFF-R gene. This study was designed to clone and characterize the 5'-regulatory region of the human BAFF-R gene and determine the mechanisms involved in its transcriptional regulation. In addition, the effects of interferon (IFN)-gamma and BAY11-7082 (inhibitor of nuclear factor [NF]-kappaB) on the expression and promoter activity of BAFF-R were examined. The results showed that the sequence between -1420 and +261 could be a core promoter region, and -1562 and -1420 bp harbored a transcriptive silencer. IFN-gamma promoted BAFF-R promoter activity and upregulated BAFF-R mRNA expression. BAY11-7082 (inhibitor of NF-kappaB) exhibited an inhibitory effect on BAFF-R promoter activity and downregulated BAFF-R mRNA expression. Our data provided novel evidence to clarify the mechanism of transcriptional regulation of BAFF-R and illustrated that IFN-gamma and NF-kappaB pathway were involved in regulating BAFF-R expression. Thus some BAFF-R-related diseases might be cured by blocking transcriptional regulation of BAFF-R and reducing its expression.
Induction of in vitro differentiation of mouse erythroleukemia cells by genistein, an inhibitor of tyrosine protein kinases. (1991)

We have found that genistein, a specific inhibitor of tyrosine protein kinases, induces in vitro erythroid differentiation of mouse erythroleukemia cells. Characterization of the induction process indicated that the genistein-induced differentiation is different from that induced by conventional inducing agents such as dimethyl sulfoxide or hexamethylene-bisacetamide. This conclusion was based upon the earlier appearance of differentiated cells, insensitivity to a specific inhibitor (dexamethasone), and responsiveness of some of the differentiation-resistant cells to genistein in the genistein-induced erythroid differentiation. Possible biological significance of this finding is discussed with respect to the involvement of protein phosphorylation (or dephosphorylation) in mouse erythroleukemia cell differentiation.
Participation and Community Development (2010)

This paper tries to put forward the argument that participation is a vehicle of community development. In order to achieve development in the community, community members should be involved directly in the process of development. Participation is participating in decision making, to choose a community project, plan it, implement it, manage it, monitor it, control it. The paper focuses on the definition of community development and participation in order to elaborate them. The main argument in this paper is: Participation is a vehicle to achieve to development that community members can involve directly in development process. This paper is theoretical in nature and the review is based on secondary materials.
Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma (2002)

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma.
β-Arrestin Scaffolding of the ERK Cascade Enhances Cytosolic ERK Activity but Inhibits ERK-mediated Transcription following Angiotensin AT1a Receptor Stimulation (2002)

beta-Arrestins are cytosolic proteins that mediate homologous desensitization of G protein-coupled receptors (GPCRs) by binding to agonist-occupied receptors and by uncoupling them from heterotrimeric G proteins. The recent finding that beta-arrestins bind to some mitogen-activated protein (MAP) kinases has suggested that they might also function as scaffolds for GPCR-stimulated MAP kinase activation. To define the role of beta-arrestins in the regulation of ERK MAP kinases, we examined the effect of beta-arrestin overexpression on ERK1/2 activation and nuclear signaling in COS-7 cells expressing angiotensin II type 1a receptors (AT1aRs). Expression of either beta-arrestin1 or beta-arrestin2 reduced angiotensin-stimulated phosphatidylinositol hydrolysis but paradoxically increased angiotensin-stimulated ERK1/2 phosphorylation. The increase in ERK1/2 phosphorylation in beta-arrestin-expressing cells correlated with activation of a beta-arrestin-bound pool of ERK2. The beta-arrestin-dependent increase in ERK1/2 phosphorylation was accompanied by a significant reduction in ERK1/2-mediated, Elk1-driven transcription of a luciferase reporter. Analysis of the cellular distribution of phospho-ERK1/2 by confocal immunofluorescence microscopy and cellular fractionation revealed that overexpression of beta-arrestin resulted in a significant increase in the cytosolic pool of phospho-ERK1/2 and a corresponding decrease in the nuclear pool of phospho-ERK1/2 following angiotensin stimulation. beta-Arrestin overexpression resulted in formation of a cytoplasmic pool of beta-arrestin-bound phospho-ERK, decreased nuclear translocation of phospho-ERK1/2, and inhibition of Elk1-driven luciferase transcription even when ERK1/2 was activated by overexpression of cRaf-1 in the absence of AT1aR stimulation. These data demonstrate that beta-arrestins facilitate GPCR-mediated ERK activation but inhibit ERK-dependent transcription by binding to phospho-ERK1/2, leading to its retention in the cytosol.
ACHIEVING AND MAINTAINING COMPLIANCE WITH THE KETOGENIC DIET (1995)

The ketogenic diet, a treatment for intractable epilepsy, is rarely initiated because it requires strict compliance with a diet that is perceived to be unpalatable. In a case study of a 15-year-old girl with uncontrolled epilepsy, we used a stimulus-choice procedure to assess relative preferences of 33 foods from the diet and to develop two treatments based on Premack's principle. The results of a multielement analysis showed that both treatments increased dietary compliance. Compliance was maintained with generalization of treatment across settings, and was associated with a 40% reduction in seizures.
The role of apoptosis in pulmonary fibrosis (2008)

Apoptosis has been defined as “gene-directed cellular self-destruction” and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies. Idiopathic pulmonary fibrosis (IPF) is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition) supporting an interaction between altered apoptosis and the pathogenesis of the disease. Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis. Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.
A Review of Bioinformatics Tools for Bio-Prospecting from Metagenomic Sequence Data (2017)

The microbiome can be defined as the community of microorganisms that live in a particular environment. Metagenomics is the practice of sequencing DNA from the genomes of all organisms present in a particular sample, and has become a common method for the study of microbiome population structure and function. Increasingly, researchers are finding novel genes encoded within metagenomes, many of which may be of interest to the biotechnology and pharmaceutical industries. However, such "bioprospecting" requires a suite of sophisticated bioinformatics tools to make sense of the data. This review summarizes the most commonly used bioinformatics tools for the assembly and annotation of metagenomic sequence data with the aim of discovering novel genes.