gebhart/patrepeval huggingface dataset:
Effects of Thyroid Hormones on the Guinea Pig1 (1970)

The adminsitration in vivo of thyroxine, its analogues or derivatives, or 131I did not cause any changes in oxygen uptake by liver homogenates in the absence or presence of glycerophosphate or fructose-l,6-diphosphate. Also, no alteration either in rates of oxidation of glycerophosphate, succinate, choline, β-hydroxybutyrate, glutamate, pyruvate and L (+) lactate or in the oxidative phosphorylating efficiency of mitochondria from liver or kindey of this species was noted. Glycerophosphate, succinate and choline dehydrogenase activities in mitochondria from liver, kidney, heart, brain and spleen were unaltered after the administration of thyroxine, its analogues or derivatives, or 131I. The cytochrome c concentration of mitochondria also failed to respond to the treatment. Glucose-6- phosphate phosphohydrolase activity in microsomes was found within the normal range in various thyroid hormone states. The activities of malic enzyme, NADP-linked isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, and NAD-linked glycerophosphate dehydrodenase in the cytoplasmic soluble fraction were also not affected. On the other hand, phospholipids, fatty acid esters and cholesterol in blood plasma were elevated very significantly after the injection of thyroxine, or some of its analogues or derivatives. Free fatty acid concentrations were slightly increased after the administration of either l-triiodothyronine or 131I, but no elevation was noted after the administration of l-thyroxine, O-methyl-dl-thyroxine, or tetraiodothyroacetic acid. (Endocrinology86: 241, 1970)
Accuracy of Clinical Diagnosis in Parkinsonism — A Prospective Study (1991)

Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 years experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M-50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.
Purification and Properties of an Intranuclear Virus-specific Antigen from Tissue Infected with Borna Disease Virus (1986)

A virus-specific antigen was extracted from brains of rats and from MDCK cells infected with Borna disease (BD) virus and purified to homogeneity by immunoaffinity chromatography and HPLC. The antigen consists of two components which are almost equal in size (38 000 mol. wt.), and it forms aggregates in its native form. The virus specificity of the two antigenic entities was confirmed by immunoblots with convalescent serum and monoclonal antibodies. Immunofluorescent staining with monoclonal antibodies and a hyperimmune serum prepared against the purified antigen showed the intranuclear fluorescence typical for BD virus-infected cells.
Ribonuclease T1: Structure, Function, and Stability (1991)

Abstract Proteins carry out the most important and difficult tasks in all living organisms. To do so, they must often interact specifically with other small and large molecules. This requires that they fold to a globular conformation with a unique active site that is used for the specific interaction. Consequently, protein folding can be regarded as the “secret of life”. Biochemists and chemists have a great interest in elucidating the mechanism by which proteins fold and in predicting the folded conformation and its stability given just the amino acid sequence. This challenge is sometimes called the “protein folding problem”. The ability to construct proteins differing in sequence by one or more amino acids and to analyze their three‐dimensional structures by X‐ray crystallography and NMR spectroscopy is a powerful tool for investigating the conformational stability and folding of proteins. Several proteins are now under intensive study by this approach. One of these is ribonuclease T1.
Search for a Third Susceptibility Gene for Maturity-Onset Diabetes of the Young: Studies With Eleven Candidate Genes (1994)

Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. This cohort of families will be useful for identifying other diabetes-susceptibility genes. Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid–binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. None of these loci showed evidence for linkage with MODY, implying that mutations in these genes do not make a major genetic contribution to the development of MODY. In addition to these linkage analyses, one or two affected subjects from each family were screened for the presence of the A to G mutation at nucleotide 3,243 of the mitochondrial tRNALeu(UUR) gene. This mutation was not found in any of these subjects. Finally, we report the localization of the gene encoding the regulatory protein of glucokinase to chromosome 2, band p22.3 and the identification of a restriction fragment length polymorphism at this locus.
Identification That KfiA, a Protein Essential for the Biosynthesis of the Escherichia coli K5 Capsular Polysaccharide, Is an α-UDP-GlcNAc Glycosyltransferase (2000)

The <i>Escherichia coli</i> K5 capsular polysaccharide consists of the repeat structure -4)GlcA-β(1,4)-GlcNAc-α(1- and requires the KfiA, KfiB, KfiC, and KfiD proteins for its synthesis. Previously, the KfiC protein was shown to be a β-UDP-GlcA glycosyltransferase, and KfiD was shown to be a UDP-Glc dehydrogenase. Here, we demonstrate that KfiA is an α-UDP-GlcNAc glycosyltransferase and that biosynthesis of the K5 polysaccharide involves the concerted action of the KfiA and KfiC proteins. By site-directed mutagenesis, we determined that the acidic motif of DDD, which is conserved between the C family of glycosyltransferases, is essential for the enzymatic activity of KfiA. In addition, by Western blot analysis, we determined that association of KfiA with the cytoplasmic membrane requires KfiC but not KfiB, whereas the interaction of KfiC with the cytoplasmic membrane was dependent on both KfiA and KfiB. Likewise, KfiB was only detectable in cytoplasmic membrane fractions when both KfiA and KfiC were present. These data suggest that the interaction between the KfiA, KfiB, and KfiC proteins is essential for the stable association of these proteins with the cytoplasmic membrane and the biosynthesis of the K5 polysaccharide.
Met Activation and Receptor Dimerization in Cancer: A Role for the Sema Domain (2005)

Ligand dependent activity of receptor tyrosine kinases is critical for modulating downstream signaling and cell proliferation. In normal cellular context, hepatocyte growth factor (HGF) regulates MET kinase activation and mediates cell proliferation, migration and motility. Recent elucidation of the MET extracellular domain suggests that the Sema domain, which bears structural similarity to other Semaphorins and Plexin family members, plays a critical role in ligand mediated receptor activation. Overexpression of MET which is observed in many cancers leads to ligand independent receptor dimerization and activation. Evidence to support a role for the Sema domain in cancer and therapeutic implications of targeting the Met Sema domain are discussed in this review.
DNA hypomethylation and unusual chromosome instability in cell lines fromICF syndrome patients (2000)

The ICF syndrome (immunodeficiency, centromeric region instability, facial anomalies) is a unique DNA methylation deficiency disease diagnosed by an extraordinary collection of chromosomal anomalies specifically in the vicinity of the centromeres of chromosomes 1 and 16 (Chr1 and Chr16) in mitogen-stimulated lymphocytes. These aberrations include decondensation of centromere-adjacent (qh) heterochromatin, multiradial chromosomes with up to 12 arms, and whole-arm deletions. We demonstrate that lymphoblastoid cell lines from two ICF patients exhibit these Chr1 and Chr16 anomalies in 61% of the cells and continuously generate 1qh or 16qh breaks. No other consistent chromosomal abnormality was seen except for various telomeric associations, which had not been previously noted in ICF cells. Surprisingly, multiradials composed of arms of both Chr1 and Chr16 were favored over homologous associations and cells containing multiradials with 3 or >4 arms almost always displayed losses or gains of Chr1 or Chr16 arms from the metaphase. Our results suggest that decondensation of 1qh and 16qh often leads to unresolved Holliday junctions, chromosome breakage, arm missegregation, and the formation of multiradials that may yield more stable chromosomal abnormalities, such as translocations. These cell lines maintained the abnormal hypomethylation in 1qh and 16qh seen in ICF tissues. The ICF-specific hypomethylation occurs in only a small percentage of the genome, e.g., ICF brain DNA had 7% less 5-methylcytosine than normal brain DNA. The ICF lymphoblastoid cell lines, therefore, retain not only the ICF-specific pattern of chromosome rearrangements, but also of targeted DNA hypomethylation. This hypomethylation of heterochromatic DNA sequences is seen in many cancers and may predispose to chromosome rearrangements in cancer as well as in ICF.
SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats (2002)

The central CB(1) cannabinoid receptor has recently been implicated in brain reward function. In the present study we evaluated first the effects of the selective CB(1) receptor antagonist, SR141716, on the motivational effects of nicotine in the rat. Administration of SR141716 (0.3 and 1 mg/kg) decreased nicotine self-administration (0.03 mg/kg/injection). SR141716 (0.3-3 mg/kg) neither substituted for nicotine nor antagonized the nicotine cue in a nicotine discrimination procedure, but dose-dependently (0.01-1 mg/kg) antagonized the substitution of nicotine for D-amphetamine, in rats trained to discriminate D-amphetamine. Secondly, using brain microdialysis, SR141716 (1-3 mg/kg) blocked nicotine-induced dopamine release in the shell of the nucleus accumbens (NAc) and the bed nucleus of the stria terminalis. To investigate whether SR141716 would block the dopamine-releasing effects of another drug of abuse, we extended the neurochemical study to the effect of ethanol, consumption of which in rodents is reduced by SR141716. Dopamine release induced by ethanol in the NAc was also reduced by SR141716 (3 mg/kg). These results suggest that activation of the endogenous cannabinoid system may participate in the motivational and dopamine-releasing effects of nicotine and ethanol. Thus, SR141716 may be effective in reduction of alcohol consumption, as previously suggested, and as an aid for smoking cessation.
Lower Urinary Tract Dysfunction in Pelvic Gynecologic Cancer: The Role of Urodynamics (2014)

The exact incidence of lower urinary tract dysfunction is not known and its pathogenesis is not completely understood. Advances in urodynamic assessment and widespread availability of a standardized technique have facilitated its exploration prior to and subsequent to the surgical management of patients with gynecologic pelvic cancer. We performed a PubMed and Medline literature search using the following keywords: bladder dysfunction, urinary dysfunction, and urodynamics and all these terms in combination with radical hysterectomy in order to analyze the role of urodynamics in patients with pelvic gynecologic cancer in the preoperative as well as in the early and late postoperative settings.
Clostridial Toxins as Therapeutic Agents: Benefits of Nature's Most Toxic Proteins (1999)

Toxins are increasingly being used as valuable tools for analysis of cellular physiology, and some are used medicinally for treatment of human diseases. In particular, botulinum toxin, the most poisonous biological substance known, is used for treatment of a myriad of human neuromuscular disorders characterized by involuntary muscle contractions. Since approval of type-A botulinum toxin by the US Food and Drug Administration in December 1989 for three disorders (strabismus, blepharospasm, and hemifacial spasm), the number of indications being treated has increased greatly to include numerous focal dystonias, spasticity, tremors, cosmetic applications, migraine and tension headaches, and other maladies. Many of these diseases were previously refractory to pharmacological and surgical treatments. The remarkable therapeutic utility of botulinum toxin lies in its ability to specifically and potently inhibit involuntary muscle activity for an extended duration. The clostridia produce more protein toxins than any other bacterial genus and are a rich reservoir of toxins for research and medicinal uses. Research is underway to use clostridial toxins or toxin domains for drug delivery, prevention of food poisoning, and the treatment of cancer and other diseases. The remarkable success of botulinum toxin as a therapeutic agent has created a new field of investigation in microbiology.
1,2,4-Triazoles. XII. Derivatives of the s-Triazolo[4,3-a]pyridine Ring System1a (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,2,4-Triazoles. XII. Derivatives of the s-Triazolo[4,3-a]pyridine Ring System1aK. T. Potts and H. R. BurtonCite this: J. Org. Chem. 1966, 31, 1, 251–260Publication Date (Print):January 1, 1966Publication History Published online1 May 2002Published inissue 1 January 1966https://pubs.acs.org/doi/10.1021/jo01339a057https://doi.org/10.1021/jo01339a057research-articleACS PublicationsRequest reuse permissionsArticle Views1005Altmetric-Citations57LEARN 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
Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC) (2005)

Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-specific survival in head and neck squamous cell carcinoma (HNSCC). To assess the prevalence of copy number gains (>4 signals per cell) and high-level amplifications (>8 signals per cell) from putative oncogenes in this chromosomal region (CCNL1, SNO, PIK3CA, TP73L), tissue microarray analysis was applied on 280 HNSCCs by fluorescence in situ hybridization. Overall frequency of additional copy numbers was 34.3% for CCNL1, 31.8% for SNO, 39.0% for PIK3CA and 38.3% for TP73L, respectively. In general, gains were more frequently detected in stage IV compared to stage I-III tumours. Performing multivariate logistic regression analysis, a significant association of CCNL1 gains and the presence of lymph node metastases was found, which was independent of anatomical site and T-stage of the primary tumour (P=0.049). Site-specific subgroup analysis further showed that copy number gains of CCNL1 and SNO occurred more frequently in oral carcinomas in advanced clinical stages as compared to N0 oral lesions (CCNL1: P=0.03; SNO: P=0.03). Finally, Kaplan-Meier analysis revealed that high-level amplifications of CCNL1 correlated with shorter overall survival of the patients. Our results indicate that CCNL1 plays a critical role in the loco-regional progression of HNSCC and may serve as an indicator for occult advanced tumour stages.
rRNA-like sequences occur in diverse primary transcripts: Implications for the control of gene expression (1997)

Many eukaryotic mRNAs contain sequences that resemble segments of 28S and 18S rRNAs, and these rRNA-like sequences are present in both the sense and antisense orientations. Some are similar to highly conserved regions of the rRNAs, whereas others have sequence similarities to expansion segments. In particular, four 18S rRNA-like sequences are found in several hundred different genes, and the location of these four sequences within the various genes is not random. One of these rRNA-like sequences is preferentially located within protein coding regions immediately upstream of the termination codon of a number of genes. Northern blot analysis of poly(A)+ RNA from different vertebrates (chicken, cattle, rat, mouse, and human) revealed that a large number of discrete RNA molecules hybridize at high stringency to cloned probes prepared from the 28S or 18S rRNA sequences that were found to match those in mRNAs. Inhibition of polymerase II activity, which prevents the synthesis of most mRNAs, abolished most of the hybridization to the rRNA probes. We consider the hypotheses that rRNA-like sequences may have spread throughout eukaryotic genomes and that their presence in primary transcripts may differentially affect gene expression.
Peptides: Chemistry and Biology (2009)

INTRODUCTION AND BACKGROUND FUNDAMENTAL CHEMICAL AND STRUCTURAL PRINCIPLES Definitions and Main Conformational Features of the Peptide Bond Building Blocks, Classification, and Nomenclature Analysis of the Covalent Structure of Peptides and Proteins Three-Dimensional Structure Methods of Structural Analysis BIOLOGY OF PEPTIDES Historical Aspects and Biological Functions Biosynthesis Selected Biologically Active Peptides PEPTIDE SYNTHESIS Principles and Objectives Protection of Functional Groups Peptide Bond Formation Racemization During Synthesis Solid-Phase Peptide Synthesis (SPPS) Biochemical Synthesis SYNTHESIS CONCEPTS FOR PEPTIDES AND PROTEINS Strategy and Tactics Solution Phase Synthesis (SPS) NEW: Solution Phase/Solid Phase-Hybrid Approaches Optimized Strategies on Polymeric Support Chemical Ligation Strategies SYNTHESIS OF SPECIAL PEPTIDES AND PEPTIDE CONJUGATES Cyclopeptides Cystine Peptides Glycopeptides Phosphopeptides Lipopeptides Sulfated Peptides PEPTIDE AND PROTEIN DESIGN, PSEUDOPEPTIDES, AND PEPTIDOMIMETICS Peptide Design Modified Peptides Peptidomimetics Pseudobiopolymers Macropeptides and De-Novo Design of Peptides and Proteins COMBINATORIAL PEPTIDE SYNTHESIS Parallel Synthesis Synthesis of Mixtures APPLICATION OF PEPTIDES AND PROTEINS NEW: General Production Strategies NEW: Improvement of the Therapeutic Potential Protein Pharmaceuticals Peptide Pharmaceuticals PEPTIDES IN PROTEOMICS NEW: Genome and Proteome NEW: Separation Methods NEW: Peptide and Protein Analysis in Proteomics NEW: Activity-Based Proteomics
A Modular Cross-Linking Approach for Exploring Protein Interactions (2003)

A method is described for the elucidation of protein-protein interactions using novel cross-linking reagents and mass spectrometry. The method incorporates (1) a modular solid-phase synthetic strategy for generating the cross-linking reagents, (2) enrichment and digestion of cross-linked proteins using microconcentrators, (3) mass spectrometric analysis of cross-linked peptides, and (4) comprehensive computational analysis of the cross-linking data. This integrated approach has been applied to the study of cross-linking between the components of the heterodimeric protein complex negative cofactor 2.
Structure of the Unphosphorylated STAT5a Dimer* (2005)

STAT proteins have the function of signaling from the cell membrane into the nucleus, where they regulate gene transcription. Latent mammalian STAT proteins can form dimers in the cytoplasm even before receptor-mediated activation by specific tyrosine phosphorylation. Here we describe the 3.21-A crystal structure of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as the C-terminal transactivation domain. The overall structure of this fragment is very similar to phosphorylated STATs. However, important differences exist in the dimerization mode. Although the interface between phosphorylated STATs is mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment dimerizes in a completely different manner via interactions between their beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can be docked onto this STAT5a core fragment dimer based on shape and charge complementarities. The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells.