gebhart/patrepeval huggingface dataset:
Autocrine CSF-1 and CSF-1 Receptor Coexpression Promotes Renal Cell Carcinoma Growth (2011)

Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Coexpression of the monocytic growth factor colony-stimulating factor (CSF)-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and antiapoptosis during regeneration of renal tubules. Here, we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were coexpressed in RCCs and TECs proximally adjacent to RCCs. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and epidermal growth factor signaling in RCCs. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R, and epidermal growth factor expression in RCCs. Furthermore, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCCs.
Relationship between sodium channel NaV1.3 expression and neuropathic pain behavior in rats (2005)

A multitude of voltage-gated sodium channel subtypes (NaV1) are expressed in primary sensory neurons where they influence excitability via their role in the generation and propagation of action potentials. Peripheral nerve injury alters the expression of several NaV1subtypes, but among these only NaV1.3 is up-regulated in dorsal root ganglia (DRG) neurons. The increased expression of NaV1.3 implicates this subtype in the development and maintenance of neuropathic pain, but its contribution to neuropathic pain behavior has not been examined. Using the spared nerve injury (SNI) model, we found that peripheral nerve lesion increased NaV1.3-like immunoreactivity (-LI) in DRG neurons and that mechanical allodynia was partially alleviated following oral administration of two NaV1 blockers, mexiletine (30 and 100 mg/kg, p.o.) and lamotrigine (30 and 100 mg/kg, p.o.). Intrathecal administration of antisense oligonucleotides (4 days) selective for NaV1.3 decreased NaV1.3 immunostaining in the DRG by 50% in the SNI model, but did not attenuate mechanical or cold allodynia. Moreover, we found that only 18% of NaV1.3 positive neurons also expressed activated transcription factor-3 (ATF3), a marker of injured neurons. We then selectively axotomized a cutaneous nerve (sural) and a muscle nerve (gastrocnemius) in order to identify if NaV1.3 up-regulation is dependent on cutaneous and/or muscle afferent activation and found that the numbers of neurons expressing NaV1.3 was proportional to the magnitude of the injury, but independent of the nature of innervation. These results suggest that NaV1.3 increases in primary sensory neurons that are not directly damaged in response to injury. Thus, although NaV1.3 is up-regulated in a subpopulation of DRG neurons after injury, reduction in the expression of NaV1.3 subtype alone is not sufficient to influence the NaV1-dependent behavioral hypersensitivity associated with nerve injury.
Behavior of diffusion, permeation and sorption of flavor compounds in vapor phase with polyethylene film. (1987)

A new method for measurement of diffusion, permeation and sorption coefficients of volatile compounds in polyethylene (PE) film was established. The activation energies for the diffusion in middle density PE (MDPE) of n-octane, ethyl caproate, n-octanal and noctanol were 14.6, 10.5, 15.0 and 19.2kcal/mol, respectively. Although the molecular volumes of penetrants were the almost same value, it was indicated that the hole volumes in the PE required for the penetrants to diffuse or jump were quite different. The enthalpy changes in sorption from vapor phase were -9.1, -8.2, -2.7 and -10.7kcal/mol, respectively, that is, all the sorption were exothermic process. The decrease in enthalpy was associated with the increase in boiling points of penetrants and the increase in affinities for PE.
Kallikrein Protease Activated Receptor (PAR) Axis: An Attractive Target for Drug Development (2012)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTKallikrein Protease Activated Receptor (PAR) Axis: An Attractive Target for Drug DevelopmentGiuseppe Caliendo*†, Vincenzo Santagada†, Elisa Perissutti†, Beatrice Severino†, Ferdinando Fiorino†, Francesco Frecentese†, and Luiz Juliano‡View Author Information† Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli "Federico II", Via D. Montesano, 49, 80131, Napoli, Italy‡ Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo 04044-020, Brazil*Phone/Fax: +39(81)678649. E-mail: [email protected]Cite this: J. Med. Chem. 2012, 55, 15, 6669–6686Publication Date (Web):May 18, 2012Publication History Received23 March 2012Published online12 June 2012Published inissue 9 August 2012https://pubs.acs.org/doi/10.1021/jm300407thttps://doi.org/10.1021/jm300407treview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views1829Altmetric-Citations15LEARN 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:Antagonists,Cancer,Inhibitors,Peptides and proteins,Receptors Get e-Alerts
AnkyrinG is associated with the postsynaptic membrane and the sarcoplasmic reticulum in the skeletal muscle fiber (1998)

Ankyrins are a multi-gene family of peripheral proteins that link ion channels and cell adhesion molecules to the spectrin-based skeleton in specialized membrane domains. In the mammalian skeletal myofiber, ankyrins were immunolocalized in several membrane domains, namely the costameres, the postsynaptic membrane and the triads. Ank1 and Ank3 transcripts were previously detected in skeletal muscle by northern blot analysis. However, the ankyrin isoforms associated with these domains were not identified, with the exception of an unconventional Ank1 gene product that was recently localized at discrete sites of the sarcoplasmic reticulum. Here we study the expression and subcellular distribution of the Ank3 gene products, the ankyrinsG, in the rat skeletal muscle fiber. Northern blot analysis of rat skeletal muscle mRNAs using domain-specific Ank3 cDNA probes revealed two transcripts of 8.0 kb and 5.6 kb containing the spectrin-binding and C-terminal, but not the serine-rich, domains. Reverse transcriptase PCR analysis of rat skeletal muscle total RNA confirmed the presence of Ank3 transcripts that lacked the serine-rich and tail domains, a major insert of 7813 bp at the junction of the spectrin-binding and C-terminal domains that was previously identified in brain Ank3 transcripts. Immunoblot analysis of total skeletal muscle homogenates using ankyrinG-specific antibodies revealed one major 100 kDa ankyrinG polypeptide. Immunofluorescence labeling of rat diaphragm cryosections showed that ankyrin(s)G are selectively associated with (1) the depths of the postsynaptic membrane folds, where the voltage-dependent sodium channel and N-CAM accumulate, and (2) the sarcoplasmic reticulum, as confirmed by codistribution with the sarcoplasmic reticulum Ca2+-ATPase (SERCA 1). At variance with ankyrin(s)G, ankyrin(s)R (ank1 gene products) accumulate at the sarcolemma and at sarcoplasmic structures, in register with A-bands. Both ankyrin isoforms codistributed over Z-lines and at the postsynaptic membrane. These data extend the notion that ankyrins are differentially localized within myofibers, and point to a role of the ankyrinG family in the organization of the sarcoplasmic reticulum and the postsynaptic membrane.
Peroxisome Proliferator–Activated Receptor α/γ Dual Agonist Tesaglitazar Attenuates Diabetic Nephropathy in db/db Mice (2007)

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors and play a central role in insulin sensitivity, lipid metabolism, and inflammation. Both PPARalpha and -gamma are expressed in the kidney, and their agonists exhibit renoprotective effects in type 2 diabetes. In the present studies, we investigated the effect of the PPARalpha/gamma dual agonist tesaglitazar on diabetic nephropathy in type 2 diabetic db/db mice. Treatment of db/db mice with tesaglitazar for 3 months significantly lowered fasting plasma glucose and homeostasis model assessment of insulin resistance levels but had little effect on body weight, adiposity, or cardiac function. Treatment with tesaglitazar was associated with reduced plasma insulin and total triglyceride levels and increased plasma adiponectin levels. Notably, tesaglitazar markedly attenuated albuminuria and significantly lowered glomerulofibrosis, collagen deposition, and transforming growth factor-beta1 expression in renal tissues of db/db mice. In cultured mesangial cells and proximal tubule cells, where both PPARalpha and -gamma were expressed, tesaglitazar treatment abolished high glucose-induced total collagen protein production and type I and IV collagen gene expression. Collectively, tesaglitazar treatment not only improved insulin resistance, glycemic control, and lipid profile but also markedly attenuated albuminuria and renal glomerular fibrosis in db/db mice. These findings support the utility of dual PPARalpha/gamma agonists in treating type 2 diabetes and diabetic nephropathy.
Mice immunized with recombinant vaccinia virus expressing dengue 4 virus structural proteins with or without nonstructural protein NS1 are protected against fatal dengue virus encephalitis (1989)

We have constructed vaccinia virus recombinants expressing dengue virus proteins from cloned DNA for use in experimental immunoprophylaxis. A recombinant virus containing a 4.0-kilobase DNA sequence that codes for three structural proteins, capsid (C), premembrane (pre-M), and envelope (E), and for nonstructural proteins NS1 and NS2a produced authentic pre-M, E, and NS1 in infected CV-1 cells. Mice immunized with this recombinant were protected against an intracerebral injection of 100 50% lethal doses of dengue 4 virus. A recombinant containing only genes C, pre-M, and E also induced solid resistance to challenge. Deletion of the putative C-terminal hydrophobic anchor of the E glycoprotein did not result in secretion of E from recombinant-virus-infected cells. Recombinants expressing only the E protein preceded by its own predicted N-terminal hydrophobic signal or by the signal of influenza A virus hemagglutinin or by the N-terminal 71 amino acids of the G glycoprotein of respiratory syncytial virus produced glycosylated E protein products of expected molecular sizes. These vaccinia virus recombinants also protected mice.
Thermal ablation of tumor cells with antibody-functionalized single-walled carbon nanotubes (2008)

Single-walled carbon nanotubes (CNTs) emit heat when they absorb energy from near-infrared (NIR) light. Tissue is relatively transparent to NIR, which suggests that targeting CNTs to tumor cells, followed by noninvasive exposure to NIR light, will ablate tumors within the range of NIR. In this study, we demonstrate the specific binding of antibody-coupled CNTs to tumor cells in vitro, followed by their highly specific ablation with NIR light. Biotinylated polar lipids were used to prepare stable, biocompatible, noncytotoxic CNT dispersions that were then attached to one of two different neutralite avidin-derivatized mAbs directed against either human CD22 or CD25. CD22(+)CD25(-) Daudi cells bound only CNTs coupled to the anti-CD22 mAb; CD22(-)CD25(+) activated peripheral blood mononuclear cells bound only to the CNTs coupled to the anti-CD25 mAb. Most importantly, only the specifically targeted cells were killed after exposure to NIR light.
Functional Anthology of Intrinsic Disorder. 1. Biological Processes and Functions of Proteins with Long Disordered Regions (2007)

Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical approach, outlines the major findings, and provides illustrative examples of biological processes and functions positively and negatively correlated with intrinsic disorder.
Controlling the enantioselectivity of enzymes by directed evolution: Practical and theoretical ramifications (2004)

A fundamentally new approach to asymmetric catalysis in organic chemistry is described based on the in vitro evolution of enantioselective enzymes. It comprises the appropriate combination of gene mutagenesis and expression coupled with an efficient high-throughput screening system for evaluating enantioselectivity (enantiomeric excess assay). Several such cycles lead to a "Darwinistic" process, which is independent of any knowledge concerning the structure or the mechanism of the enzyme being evolved. The challenge is to choose the optimal mutagenesis methods to navigate efficiently in protein sequence space. As a first example, the combination of error-prone mutagenesis, saturation mutagenesis, and DNA-shuffling led to a dramatic enhancement of enantioselectivity of a lipase acting as a catalyst in the kinetic resolution of a chiral ester. Mutations at positions remote from the catalytically active center were identified, a surprising finding, which was explained on the basis of a novel relay mechanism. The scope and limitations of the method are discussed, including the prospect of directed evolution of stereoselective hybrid catalysts composed of robust protein hosts in which transition metal centers have been implanted.
The Synthesis of Branched Oligonucleotides as Signal Amplification Multimers for Use in Nucleic Acid Assays (1989)

Abstract Branched oligonucleotides have been synthesized using phosphoramidite derivatives with two protected hydroxyl functions. These molecules are employed for a label amplification strategy used in DNA probe diagnostics.
Interruption of Recurrent Clostridium difficile-Associated Diarrhea Episodes by Serial Therapy with Vancomycin and Rifaximin (2007)

Eight women who each experienced 4-8 episodes of Clostridium difficile-associated diarrhea were given a 2-week course of rifaximin therapy when they were asymptomatic, immediately after completing their last course of vancomycin therapy. Seven of the 8 patients experienced no further diarrhea recurrence. The patient who had a recurrence responded to a second course of rifaximin therapy, but rifaximin-resistant C. difficile was recovered after treatment. A controlled trial for treating recurrent Clostridium difficile-associated diarrhea appears to be warranted.
Molecular recognition. II—Discrimination of specific and non-specific intermolecular interactions by means of magnetic resonance spectroscopy (1998)

The interactions of adenine- and benzimidazole-type substrates with a model receptor (Rebek's cleft) and benzoic acid were studied by magnetic resonance spectroscopy. The spectra reveal dynamic phenomena which are analysed in terms of static, two-jump and two-site models. The interpretation provides information on the inter- and intramolecular structures and allows specific interactions to be distinguished from non-specific interactions. ©1998 John Wiley & Sons, Ltd.
Minor cucurbitane-glycosides from fruits of Siraitia grosvenori (Cucurbitaceae). (1990)

From fruits of Siraitia grosvenori, a Chinese medicinal plant, a new minor glycoside and four known minor cucurbitane glycosides, siamenoside I (sweet), 11-oxo-mogroside V (sweet), and mogrosides IIE and IIIE (both tasteless) were isolated together with mogrosides IV and V (both sweet) previously isolated from this fruit by Arihara et al. Structure of the new testeless glycoside called mogroside III was elucidated as 3-O-β-D-glucopyranosyl- 24-O-β-gentiobiosyl-mogrol. The relative sweetness of siamenoside I to sucrose was estimated ×563, making this the sweetest compound among the cucurbitane-glycosides so far isolated. The structure-taste relationship of cucurbitane-glycosides is also described.
Efficientl-Serine Production from Methanol and Glycine by Resting Cells ofMethylobacteriumsp. Strain MN43 (1996)

Resting cells of methanol-utilizing microorganisms isolated from soils were examined for L-serine production under conditions in which L-serine-degradation was suppressed. Strain MN43, a facultative methylotrophic bacterium identified as a Methylobacterium sp., was selected for further studies. Under the optimal conditions, 65 mg/ml L-serine was produced by this bacterium from 50 mg/ml glycine and 104 mg/ml methanol in 5 days, with a molar conversion ratio from glycine to L-serine of 93%. This production is the highest so far reported for microbes producing L-serine.
Generalized transduction of serotype 1/2 and serotype 4b strains of Listeria monocytogenes (2000)

This is the first report of generalized transduction in the gram-positive, food-borne pathogen Listeria monocytogenes. Bacteriophages were isolated from the environment and from lysogens, or were obtained from other laboratories. Of the 59 bacteriophages tested, 34 proved to be capable of transduction. We exploited the ability of L. monocytogenes to grow at room temperature and isolated bacteriophages that were incapable of growth at 37 degrees C. Transductions at this temperature therefore eliminated transductant killing and lysogeny, as did inclusion of citrate and the use of a low multiplicity of infection. Transducing bacteriophages were found for each of the well-characterized L. monocytogenes strains: EGD, 10403, Mack (serotype1/2a), L028 (serotype 1/2c), Scott A (serotype 4b) and strains from the Jalisco and Halifax, Nova Scotia outbreaks (serotype 4b). P35 (phiLMUP35) is a particularly useful generalized transducing bacteriophage with a wide host range (75% of all serotype 1/2 strains tested). Its disadvantages are that it is small and transduction is relatively infrequent. U153(phiCU-SI153/95) is larger than P35 and transduction frequency increased 100-fold, but it has a very narrow host range. We demonstrated interstrain transduction and used transduction to test linkage between transposon insertions and mutant phenotypes in a variety of strains.
Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease (2003)

Mucopolysaccharidosis IVA is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme required for the stepwise degradation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). To generate a model for studies of the pathophysiology and of potential therapies, we disrupted exon 2 of Galns, the homologous murine gene. Homozygous Galns-/- mice have no detectable GALNS enzyme activity and show increased urinary glycosaminoglycan (GAGs) levels. These mice accumulate GAGs in multiple tissues including liver, kidney, spleen, heart, brain and bone marrow. At 2 months old, lysosomal storage is present primarily within reticuloendothelial cells such as Kupffer cells and cells of the sinusoidal lining of the spleen. Additionally, by 12 months old, vacuolar change is observed in the visceral epithelial cells of glomeruli and cells at the base of heart valves but it is not present in parenchymal cells such as hepatocytes and renal tubular epithelial cells. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage. KS and C6S were more abundant in the cytoplasm of corneal epithelial cells of Galns-/- mice compared with wild-type mice by immunohistochemistry. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, targeted disruption of the murine Galns gene has produced a murine model, which shows visceral storage of GAGs but lacks the skeletal features. The complete absence of GALNS in mutant mice makes them useful for studies of pharmacokinetics and tissue targeting of recombinant GALNS designed for enzyme replacement.
Mobile handset power amplifiers (2009)

Handset RF power amplifier (PA) module design is a complex process that involves a great number of tradeoffs. High efficiency, small size, and low cost are the main design goals. The incessant size reduction of handsets and their increased functionality will continue to put pressure on PA designers to achieve a high level of performance in even smaller packages by developing novel integration and packaging technologies. The handset PA module industry is severely challenged by cost and size. It is hard to justify any improvement in performance if it comes at a higher price tag or larger dimensions. These facts have prevented many technological advances, e.g., Chireix, Doherty and Kahn techniques, MEMS, reconfigurable matching networks, gallium nitride, etc., from being widely utilized today in handset PA modules. However, a breakthrough in any of these technologies could enable its widespread adoption.