gebhart/patrepeval huggingface dataset:
Beta-Adrenergic receptor modulation of adipocyte metabolism and growth (2002)

Abstract β -Adrenergic receptor ( β AR) agonists reduce body fat in mammals and birds. Synthetic lipid metabolism is decreased in β AR agonist-treated animals or in agonist-treated adipocytes in vitro. Degradative lipid metabolism is increased by β AR agonists in adipocytes in vitro and in vivo. The β AR agonist effects are blocked by β AR antagonists. In mammalian tissues, there are at least three distinct β AR subtypes; β -1 ( β 1AR), β -2 ( β 2AR), and β -3 ( β 3AR). Individual tissues have different proportions of subtypes. For example, greater than 85% of the β AR in rat heart is β 1AR, in guinea pig lung is β 2AR, and in rat adipose tissue is β 3AR. Subtype distribution within a tissue varies with species (e.g., human heart has 65% β 1AR and porcine adipocytes have less than 10% β 3AR). There is species variation in the amino acid sequence of a β AR subtype. Thus, it is expected that some β AR agonists would have different effects in the same tissue in different species because of different β AR subtype distribution and(or) amino acid sequence. In support of these concepts, the pharmacology of β AR agonists and antagonists in adipocytes is in many cases species-specific. Cloning of individual β AR subtypes allows determination of the pharmacology of subtypes from that species. For example, the pharmacology of the cloned porcine β 1AR, β 2AR, and β 3AR indicates selected agonists or antagonists can be used to assess the proportion of β AR subtypes. Nucleic acid sequences of the subtypes were used to prepare probes to quantify the subtype mRNA. The pharmacological and mRNA data agree rather closely and indicate porcine adipocytes contain over 70% β 1AR. The effects produced by a β AR agonist (or antagonist) on adipose tissue in vivo depend not only on the species and the adipocyte β AR subtype distribution, but also on the pharmacokinetics and pharmacodynamics of the compound in that species, including blood flow to the tissue, and the multiple metabolic and endocrine effects of the compound in other tissues of the body. In short, it is expected that individual β AR agonists would have somewhat different effects in different species.
Effects of ionizing radiation on a plant genome: analysis of two Arabidopsis transparent testa mutations. (1992)

Ionizing radiation is known to cause chromosomal alterations such as inversions and deletions and has been used extensively for inducing mutations. In Arabidopsis, two methods for the isolation of genes identified on the basis of mutant phenotypes--genomic subtraction and chromosome walking--either rely on or are greatly facilitated by the availability of these types of mutations. This article gives a detailed characterization of ionizing radiation-induced mutations in plants. The Arabidopsis genes encoding chalcone flavanone isomerase (CHI) and dihydroflavonol 4-reductase (DFR) were cloned and found to correspond to two transparent testa loci. A CHI allele, generated by fast-neutron irradiation, consisted of an inversion within the gene. A 272-bp fragment from 38 centimorgans away on the same chromosome was transferred to one end of this inversion. A DFR allele, induced by x-irradiation, contained two deletions and an inversion of the 2.8-centimorgan intervening region. Sequence analysis of the break points in both mutants indicate that repair of radiation-induced damage involves mechanisms similar or identical to those that mediate the integration of foreign sequences into the genome. The chromosome rearrangements found in these mutants have important implications for the use of ionizing radiation-induced alleles in classical and molecular genetic experiments in plants.
Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis (2006)

These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.
The Protective Effect of Tribulus terrestris in Diabetes (2006)

Tribulus terrestris L (TT) is used in the Arabic folk medicine to treat various diseases. The aim of this article was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes. Rats were divided into six groups and treated with either saline, glibenclamide (Glib), or TT for 30 days. Rats in group 1 were given saline after the onset of streptozotocin (STZ)-induced diabetes; the second diabetic group was administered Glib (10 mg/kg body weight). The third diabetic group was treated with the TT extract (2 g/kg body weight), while the first, second, and third nondiabetic groups were treated with saline solution, Glib, and TT extract, respectively. At the end of the experiment, serum and liver samples were collected for biochemical and morphological analysis. Levels of serum alanine aminotransferase (ALT) and creatinine were estimated. In addition, levels of malondialdehyde (MDA) and reduced glutathione (GSH) were assayed in the liver. The tested TT extract significantly decreased the levels of ALT and creatinine in the serum (P < 0.05) in diabetic groups and lowered the MDA level in liver (P < 0.05) in diabetic and (P < 0.01) nondiabetic groups. On the other hand, levels of reduced GSH in liver were significantly increased (P < 0.01) in diabetic rats treated with TT. Histopathological examination revealed significant recovery of liver in herb-treated rats. This investigation suggests that the protective effect of TT for STZ-induced diabetic rats may be mediated by inhibiting oxidative stress.
NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing (2006)

We have previously demonstrated the use of pyrosequencing to investigate NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog] mutations in melanoma biopsies. Here, we expanded the analysis to include BRAF (V-raf murine sarcoma viral oncogene homolog B1), another member of the Ras-Raf-mitogen-activated protein kinase (MAPK) signalling pathway, and analysed a total of 294 melanoma tumours from 219 patients. Mutations in BRAF exons 11 and 15 were identified in 156 (53%) tumours and NRAS exon 2 mutations in 86 (29%) tumours. Overall, mutations in NRAS or BRAF were found in 242 of 294 tumours (82%) and were found to be mutually exclusive in all but two cases (0.7%). Multiple metastases were analysed in 57 of the cases and mutations were identical in all except three, indicating that BRAF and NRAS mutations occur before metastasis. Association with preexisting nevi was significantly higher in BRAF mutated tumours (P=0.014). In addition, tumours with BRAF mutations showed a significantly more frequent moderate to pronounced infiltration of lymphocytes (P=0.013). NRAS mutations were associated with a significantly higher Clark level of invasion (P=0.022) than BRAF mutations. Age at diagnosis was significantly higher in tumours with NRAS mutations than in those with BRAF mutations (P=0.019). NRAS and BRAF mutations, however, did not influence the overall survival from time of diagnosis (P=0.7). In conclusion, the separate genotypes were associated with differences in several key clinical and pathological parameters, indicating differences in the biology of melanoma tumours with different proto-oncogene mutations.
Characterization of the Localization and Proteolytic Activity of the SUMO-specific Protease, SENP1 (2003)

Modification of proteins by small ubiquitin-like modifier (SUMO) plays an important role in the function, compartmentalization, and stability of target proteins, contributing to the regulation of diverse processes. SUMO-1 modification can be regulated not only at the level of conjugation; it may also be reversed by a class of proteases known as the SUMO-specific proteases. However, current understanding of the regulation, specificity, and function of these proteases remains limited. In this study, we characterize aspects of the compartmentalization and proteolytic activity of the mammalian SUMO-specific protease, SENP1, providing insight into its function and regulation. We demonstrate the presence of a single nonconsensus nuclear localization signal within the N terminus of the protein, the mutation of which results in pronounced cytoplasmic accumulation in contrast to the nuclear accumulation of the parental protein. In addition, we observe that the N terminus of the protein may be essential for the correct regulation of the protease, since expression of the core domain alone results in limited expression and loss of SUMO-1, indicative of constitutive catalytic activity. Consistent with the prediction that the protease is a member of the cysteine family of proteases, we mutated a key cysteine residue and observed that expression of this catalytic mutant had a dominant negative phenotype, resulting in the accumulation of high molecular weight SUMO-1 conjugates. Furthermore, we demonstrate that SENP1 may itself be a target for SUMO-1 modification occurring at a nonconsensus site. Finally, we demonstrate that SENP1 localization is influenced by expression and localization of SUMO-1-conjugated target proteins within the cell.
CFTR Activator Increases Intestinal Fluid Secretion and Normalizes Stool Output in a Mouse Model of Constipation (2016)

CFTR<sub>act</sub>-J027 or alternative small-molecule CFTR-targeted activators may be efficacious for the treatment of constipation.
Recombinant Antibody Technology: Its Advent and Advances (1993)

(1993). Recombinant Antibody Technology: Its Advent and Advances. Cancer Investigation: Vol. 11, No. 6, pp. 714-723.
Classification of Chronic Daily Headache by International Headache Society Criteria: Limits and New Proposals (1995)

We conducted a retrospective study of 150 patients with chronic daily headache (CDH) to determine how to categorize their headache according to the classification of the International Headache Society (IHS). All patients were first evaluated at Parma and Pavia Headache Centres (from January 1992 to March 1993) and had had headache for at least 15 days a month during the previous 6 months. Four patients were thereafter excluded due to poor reliability. The 146 patients who met our CDH criteria (92 with and 54 without clear-cut migraine attacks) could be classified into four groups: (i) chronic tension-type headache (CTTH)--27 patients; (ii) coexisting migraine plus CTTH--65 patients; (iii) unclassifiable daily headache--27 patients; and (iv) migraine and an unclassifiable interval headache--27 patients. Seventy-two percent of patients with CDH had migraine as the initial form of their headache. We therefore propose to revise the IHS classification for migraine, taking into account its evolution, and add two subcategories, migraine with interparoxysmal headache and chronic migraine.
Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting (2016)

Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.
The Arabidopsis 1-Aminocyclopropane-1-Carboxylate Synthase Gene 1 Is Expressed during Early Development (1993)

Renato Alberto Rodrigues-Pousada, Riet De Rycke, , Wim Van Caeneghem, Gilbert Engler, Marc Van Montagu, Dominique Van Der Straeten, The Arabidopsis 1-Aminocyclopropane-1-Carboxylate Synthase Gene 1 Is Expressed during Early Development, The Plant Cell, Vol. 5, No. 8 (Aug., 1993), pp. 897-911
Netrin-3, a Mouse Homolog of Human NTN2L, Is Highly Expressed in Sensory Ganglia and Shows Differential Binding to Netrin Receptors (1999)

The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2, have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1, has been reported. We report the identification of a second mouse netrin gene, which we name netrin-3. Netrin-3 does not appear to be the ortholog of chick netrin-2 but is the ortholog of a recently identified human netrin gene termed NTN2L ("netrin-2-like"), as evidenced by a high degree of sequence conservation and by chromosomal localization. Netrin-3 is expressed in sensory ganglia, mesenchymal cells, and muscles during the time of peripheral nerve development but is largely excluded from the CNS at early stages of its development. The murine netrin-3 protein binds to netrin receptors of the DCC (deleted in colorectal cancer) family [DCC and neogenin] and the UNC5 family (UNC5H1, UNC5H2 and UNC5H3). Unlike chick netrin-1, however, murine netrin-3 binds to DCC with lower affinity than to the other four receptors. Consistent with this finding, although murine netrin-3 can mimic the outgrowth-promoting activity of netrin-1 on commissural axons, it has lower specific activity than netrin-1. Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC.
The p-(methylsulfinyl)benzyl group: a trifluoroacetic acid (TFA)-stable carboxyl-protecting group readily convertible to a TFA-labile group (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe p-(methylsulfinyl)benzyl group: a trifluoroacetic acid (TFA)-stable carboxyl-protecting group readily convertible to a TFA-labile groupJames M. Samanen and Ester BrandeisCite this: J. Org. Chem. 1988, 53, 3, 561–569Publication Date (Print):February 1, 1988Publication History Published online1 May 2002Published inissue 1 February 1988https://pubs.acs.org/doi/10.1021/jo00238a016https://doi.org/10.1021/jo00238a016research-articleACS PublicationsRequest reuse permissionsArticle Views727Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Beating Bias in the Directed Evolution of Proteins: Combining High‐Fidelity on‐Chip Solid‐Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction (2017)

Saturation mutagenesis (SM) constitutes a widely used technique in the directed evolution of selective enzymes as catalysts in organic chemistry and in the manipulation of metabolic paths and genomes, but the quality of the libraries is far from optimal due to the inherent amino acid bias. Herein, it is shown how this fundamental problem can be solved by applying high-fidelity solid-phase chemical gene synthesis on silicon chips followed by efficient gene assembly. Limonene epoxide hydrolase was chosen as the catalyst in the model desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)- and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM library, produced by simultaneous randomization at several residues by using a reduced amino acid alphabet, and the respective synthetic library were constructed and compared. Statistical analysis at the DNA level with massive sequencing demonstrates that, in the synthetic approach, 97 % of the theoretically possible DNA mutants are formed, whereas the traditional SM library contained only about 50 %. Screening at the protein level also showed the superiority of the synthetic library; many highly (R,R)- and (S,S)-selective variants being discovered are not found in the traditional SM library. With the prices of synthetic genes decreasing, this approach may point the way to future directed evolution.
Recovery of Spores from Thermophilic Dairy Bacilli and Effects of Their Surface Characteristics on Attachment to Different Surfaces (2007)

Spores from four Geobacillus spp. were isolated from a milk powder manufacturing line in New Zealand. Liquid sporulation media produced spore yields of approximately 10(7) spores ml(-1); spores were purified using a two-phase system created with polyethylene glycol 4000 and 3 M phosphate buffer. The zeta potentials of the spores from the four isolates ranged from -10 to -20 mV at neutral pH, with an isoelectric point between pH 3 and 4. Through contact angle measurements, spores were found to be hydrophilic and had relative hydrophobicity values of 10 to 40%, as measured by the microbial adhesion to hexadecane assay. The most hydrophilic spore isolate with the smallest negative charge attached in the highest numbers to Thermanox and stainless steel (1 x 10(4) spores cm(-2)), with fewer spores attaching to glass (3 x 10(3) spores cm(-2)). However, spores produced by the other three strains attached in similar numbers (P > 0.05) to all substrata (approximately 1 x 10(3) spores cm(-2)), indicating that there was no simple relationship between individual physicochemical interactions and spore adherence. Therefore, surface modifications which limit the attachment of one strain may not be effective for all stains, and control regimens need to be devised with reference to the characteristics of the particular strains of concern.
DAS181, A Novel Sialidase Fusion Protein, Protects Mice from Lethal Avian Influenza H5N1 Virus Infection (2007)

Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential.
Assessing the Regioselectivity of OleD-Catalyzed Glycosylation with a Diverse Set of Acceptors (2013)

To explore the acceptor regioselectivity of OleD-catalyzed glucosylation, the products of OleD-catalyzed reactions with six structurally diverse acceptors flavones- (daidzein), isoflavones (flavopiridol), stilbenes (resveratrol), indole alkaloids (10-hydroxycamptothecin), and steroids (2-methoxyestradiol)-were determined. This study highlights the first synthesis of flavopiridol and 2-methoxyestradiol glucosides and confirms the ability of OleD to glucosylate both aromatic and aliphatic nucleophiles. In all cases, molecular dynamics simulations were consistent with the determined product distribution and suggest the potential to develop a virtual screening model to identify additional OleD substrates.
A Review of Randomized Clinical Trials in Tinnitus (1999)

Nonspecific support and counseling are probably helpful, as are tricyclic antidepressants in severe cases. Benzodiazepines, newer antidepressants, and electrical stimulation deserve further study. Future tinnitus therapeutic research should emphasize adequate sample size, open trials before RCTs, careful choice of outcome measures, and long-term follow-up.
Fracture of the acetabulum during insertion of an oversized hemispherical component. (1995)

A hemispherical metal-backed acetabular component that was oversized by two or four millimeters was introduced without cement into thirty fresh or embalmed cadaveric acetabula that were fifty, fifty-two, fifty-four, fifty-six, or fifty-eight millimeters in diameter. Manual tapping was used to insert the component into ten fresh and ten embalmed specimens, and a materials testing machine was used for the remaining five fresh and five embalmed specimens. The magnitude of force and the number of pulses necessary to seat the component were determined for the insertions performed with the materials testing machine; 2000 and 3000 newtons of force were required to insert the cups that were oversized by two and four millimeters, respectively. Visual and radiographic assessments were used to identify any resulting acetabular fractures. Over-all, eighteen (60 per cent) of the thirty acetabular specimens fractured. Of the eighteen fractures, only fifteen were detectable radiographically: ten on en face or lateral radiographs of the cup and five only on oblique radiographs of the cup. The remaining three fractures were apparent only after the removal of the acetabular component.(ABSTRACT TRUNCATED AT 250 WORDS)