Miracle-dz/UniFAR-FTUs huggingface dataset:
Florea and Cohn Autonomic Nervous System and Heart Failure 1817

Activation of the sympathetic nervous system (SNS) and inhibition of the parasympathetic system have long been recognized as manifestations of the clinical syndrome of heart failure (HF), presumably as a consequence of hemodynamic changes associated with the alteration in cardiac function. The possibility that this autonomic imbalance contributes directly to the progression of the disease process was postulated in the 1990s with evidence that inhibition of the sympathetic drive to the heart through β-receptor blockade favorably affected the course of the disease. Numerous drugs and devices that interfere with this activation pattern have since been studied as therapeutic means to alter the natural history of HF. The purpose of the present review is to re-explore the basic cellular mechanisms of enhanced sympathetic activity, to examine the data supporting a contributory role of these autonomic functional alterations on the course of HF, to evaluate the evidence for clinical effectiveness of these pharmacological and device interventions critically, and to consider the future role of autonomic nervous system modifiers in the management of this increasingly common and lethal disease process. The cardiac autonomic nervous system consists of 2 branches, the sympathetic and the parasympathetic systems, that work in a delicately tuned, yet opposing fashion in the heart. These branches differ in their neurotransmitters and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Both sympathetic and the parasympathetic branches of the autonomic nervous system are composed of afferent and efferent, as well as interneuronal fibers. Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart into the underlying myocardium and end as sympathetic nerve terminals reaching the Review
Promotion of periostin expression contributes to the migration of Schwann cells

ABSTRACT Neuregulin ligands and their ErbB receptors are important for the development of Schwann cells, the glial cells of the peripheral nervous system (PNS). ErbB3 deficiency is characterized by a complete loss of Schwann cells along axons of the peripheral nerves, impaired fasciculation and neuronal cell death. We performed comparative gene expression analysis of dorsal root ganglia (DRG) explant cultures from ErbB3-deficient and wild-type mice in order to identify genes that are involved in Schwann cell development and migration. The extracellular matrix (ECM) gene periostin was found to exhibit the most prominent down regulation in ErbB3-deficient DRG. Expression analysis revealed that the periostin-expressing cell population in the PNS corresponds to Schwann cell precursors and Schwann cells, and is particularly high in migratory Schwann cells. Furthermore, stimulation of Schwann cells with neuregulin-1 (NRG1) or transforming growth factor β (TGFβ-1) resulted in an upregulation of periostin expression. Interestingly, DRG explant cultures of periostin-deficient mice revealed a significant reduction of the number of migrating Schwann cells. These data demonstrate that the expression of periostin is stimulated by ErbB ligand NRG1 and influences the migration of Schwann cell precursors. Summary: Our data demonstrate that the expression of periostin is stimulated by the ErbB ligand NRG1 and promotes the migration of Schwann cell precursors.
Dopamine D2 receptors mediate glomerular hyperfiltration due to amino acids.

Renal dopamine has been proposed to be involved in the regulation of glomerular filtration rate (GFR). Because inhibition of dopamine D2 receptors abolishes the renal hyperfiltration due to amino acid load, we tested the hypothesis that pharmacological activation of D2-like receptors mimicked this renal response. In anesthetized rats, quinpirole (0.3 microgram . 100 g-1 . min-1), an agonist for receptors of the D2-like family, caused an increase in GFR by 20 +/- 2%, which corresponded to that provoked by infusion of an 10% amino acid solution. The D2 receptor antagonist S(-)-sulpiride that acts both centrally and peripherally completely abolished the renal hemodynamic response to quinpirole and to amino acids whereas domperidone, a peripherally acting D2 receptor antagonist, inhibited this hyperfiltration only in part. Urinary dopamine excretion increased in response to amino acid infusion whether GFR increased or not. We conclude that, in anesthetized rats, dopamine D2 receptors contribute to the amino acid-induced hyperfiltration and that both central and peripheral receptors might be involved, whereas dopamine excreted into the urine does not appear to play a functional role in this renal hemodynamic response.
Preparation of Papers in Two-Column Format

This paper presents a thermal model of a power transformer in the form of simple equivalent circuit. The model is established to calculate the top oil and hot spot temperatures. The model parameters are obtained from manufacturer test data and an electromagnetic analysis using finite element method (FEM). The model results are compared with measured data obtained from 250 MVA, 230±8×1.5%/118/21 kV ONAF transformer equipped with fiber optic probes and tested according to a load cycle comprising a short time load up to 2.1 pu. The results are additionally compared with the conventional equations of the IEEE clause 7.
SH 2 Domain Containing Protein Tyrosine Phosphatase 2 Regulates Concanavalin A-dependent Secretion and Activation of Matrix Metalloproteinase 2 via the Extracellular Signal-regulated Kinase and p 38 Pathways 1

We investigated the role of SH2 domain containing protein tyrosine phosphatase (SHP) 2 in Concanavalin A (Con A) -dependent signaling that leads to the augmented secretion and activation of matrix metalloproteinase (MMP) 2. In cells expressing mutant SHP-2 in which 65 amino acids in the SH2-N domain were deleted, we found that production, secretion, and proteolytic activation of MMP-2 in response to Con A treatment was severely impaired. Under Con A stimulation, complex formation of SHP-2 with SOS-1 and Grb-2 together with the activation of Ras signaling was clearly observed in wild-type cells, but not in SHP-2 mutant cells. In wild-type cells, Con A-treatment activated dual signaling pathways, extracellular signal-regulated kinase (Erk) and p38, in a Rasdependent manner, whereas Con A-dependent activation of these signaling pathways was absent in SHP-2 mutant cells. In addition, pretreatment of wild-type cells with U0126, a potent inhibitor for mitogen-activated protein/ERK kinase 1, or with SB203580, a specific inhibitor for p38, significantly inhibited the Con A-dependent secretion and activation of MMP-2. However, overexpression of active mitogen-activated protein/ ERK kinase 1 in SHP-2 mutant cells could not induce clear activation of MMP-2 secretion, although these cells responded well to the Con A treatment in a p38-dependent manner. Finally, reintroduction of wildtype SHP-2 into SHP-2 mutant cells rescued Erk and p38 activation, and also MMP-2 secretion, whereas dominant-negative SHP-2 could block the Con A-dependent activation of Erk and p38. Taken together, our results strongly suggest that SHP-2 plays a critical role as a positive mediator for Con A-dependent activation of MMP-2 secretion via Ras-Erk and Ras-p38 signalings.
Overview of pleiotropic effects of platelet P2Y12 receptor inhibitors

Summary Dual antiplatelet therapy consisting of one of the P2Y12 receptor inhibitors in conjunction with aspirin is the mainstay of treatment for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary interventions (PCI). In recent years, multiple extra-platelet features of P2Y12 receptor antagonists have been reported in numerous clinical trials. The aim of this review is to summarise reported pleiotropic effects of clopidogrel, prasugrel, ticagrelor and other P2Y12 receptor blockers. We included observations made both in human and in animal models, together with proposed mechanisms of action for described features. If confirmed in randomised studies and properly applied to everyday practice, the observed extra-platelet actions could enable us to improve efficacy of ACS and post-PCI treatment, as well as to confine mortality and occurrence rate of cardiovascular events.
Le « Drake Manuscript » de la P. Morgan Library : un document exceptionnel en marge des « nouveaux horizons » français

« L'histoire naturelle des Indes » ou le « Drake manuscript », manuscrit a peintures de la fin du 16 eme siecle est un document important sur la region caraibe. Redige, apparemment, par un protestant, il presente les tentatives de conversions des populations « sans foi » et les dogmes protestants tout en ecartant la violence de la conquete.
Parasite-Derived Proteins for the Treatment of Allergies and Autoimmune Diseases

The morbidity associated with atopic diseases and immune dysregulation disorders such as asthma, food allergies, multiple sclerosis, atopic dermatitis, type 1 diabetes mellitus, and inflammatory bowel disease has been increasing all around the world over the past few decades. Although the roles of non-biological environmental factors and genetic factors in the etiopathology have been particularly emphasized, they do not fully explain the increase; for example, genetic factors in a population change very gradually. Epidemiological investigation has revealed that the increase also parallels a decrease in infectious diseases, especially parasitic infections. Thus, the reduced prevalence of parasitic infections may be another important reason for immune dysregulation. Parasites have co-evolved with the human immune system for a long time. Some parasite-derived immune-evasion molecules have been verified to reduce the incidence and harmfulness of atopic diseases in humans by modulating the immune response. More importantly, some parasite-derived products have been shown to inhibit the progression of inflammatory diseases and consequently alleviate their symptoms. Thus, parasites, and especially their products, may have potential applications in the treatment of autoimmune diseases. In this review, the potential of parasite-derived products and their analogs for use in the treatment of atopic diseases and immune dysregulation is summarized.
Maternal Haploid, a Metalloprotease Enriched at the Largest Satellite Repeat and Essential for Genome Integrity in Drosophila Embryos

The incorporation of the paternal genome into the zygote during fertilization requires chromatin remodeling. The maternal haploid (mh) mutation in Drosophila affects this process and leads to the formation of haploid embryos without the paternal genome. mh encodes the Drosophila homolog of SPRTN, a conserved protease essential for resolving DNA–protein cross-linked products. Here we characterize the role of MH in genome maintenance. It is not understood how MH protects the paternal genome during fertilization, particularly in light of our finding that MH is present in both parental pronuclei during zygote formation. We showed that maternal chromosomes in mh mutant embryos experience instabilities in the absence of the paternal genome, which suggests that MH is generally required for chromosome stability during embryogenesis. This is consistent with our finding that MH is abundantly present on chromatin throughout the cell cycle. Remarkably, MH is prominently enriched at the 359-bp satellite repeats during interphase, which becomes unstable without MH. This dynamic localization and specific enrichment of MH at the 359 repeats resemble that of Topoisomerase 2 (Top2), suggesting that MH regulates Top2, possibly as a protease for the resolution of Top2-DNA intermediates. We propose that maternal MH removes proteins specifically enriched on sperm chromatin. In the absence of that function, paternal chromosomes are precipitously lost. This mode of paternal chromatin remodeling is likely conserved and the unique phenotype of the Drosophila mh mutants represents a rare opportunity to gain insights into the process that has been difficult to study.
Increase in urinary leukotriene LTE4 levels in acute asthma: correlation with airflow limitation

Background: Leukotrienes play a key role in the pathophysiology of chronic asthma. Activation of leukotriene pathways is accompanied by rises in detectable urinary levels of leukotriene E4 (LTE4). The relationship between urinary LTE4 levels and factors associated with acute asthma has not been determined. Methods: Adults aged 15–54 years presenting with moderate to severe acute asthma were evaluated at emergency departments in 16 US sites. Forced expiratory volume in 1 second (FEV1) was measured during the first 60 minutes after arrival and at specified times until discharge or admission. Urine samples for measurement of LTE4 levels were obtained either on arrival at the study site and/or before discharge. Patients were seen 2 weeks later for follow up, at which time repeat FEV1 measurements and urine samples for LTE4 were obtained. Results: One hundred and eighty four patients were evaluated; LTE4 results from both the acute and follow up periods were available for analysis in 146. Urinary LTE4 levels were increased during asthma exacerbations compared with levels obtained 2 weeks later (geometric means 111.7 and 75.6 pg/mg creatinine, respectively, mean percentage change −32.3; 95% confidence interval (CI) for the mean percentage change −39.6 to −24.3, p<0.001). The correlation between improvement in FEV1 and decline in LTE4 over the 2 week interval was significant (p<0.001, r = 0.43). Conclusions: Activation of leukotriene pathways in acute asthma is correlated with the degree of airflow obstruction, and resolution of the asthma exacerbation is associated with a reduction in leukotriene levels.
A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage.

BACKGROUND This randomized controlled trial compared the use of sublingual misoprostol with or without an additional 1 week course of sublingual misoprostol for the medical management of silent miscarriage. METHODS A total of 180 women who had silent miscarriage (<13 weeks) was given 600 microg of misoprostol every 3 h for a maximum of three doses. These women were randomized into two groups: (i) no extended course of misoprostol or (ii) an extended course of sublingual misoprostol 400 microg daily for 1 week. The primary outcome measure was complete miscarriage rate. RESULTS The success rates for complete miscarriage were similar in both groups (group 1: 92.2%; 95% CI: 86.1-97.5% and group 2: 93.2%; 95% CI: 84.6-96.8%). There were no serious complications. The incidence of diarrhoea was higher (P < 0.01) in the group with an extended course of sublingual misoprostol. Other side-effects were similar. CONCLUSION Sublingual misoprostol is useful for the management of silent miscarriage. An additional 1 week course of sublingual misoprostol did not improve the success rate or shorten the duration of vaginal bleeding. Instead, it increased the incidence of diarrhoea.
Crystal structure and resonance Raman studies of protocatechuate 3,4-dioxygenase complexed with 3,4-dihydroxyphenylacetate.

The crystal structure of the anaerobic complex of Pseudomonas putida protocatechuate 3,4-dioxygenase (3,4-PCD) bound with the alternative substrate, 3,4-dihydroxyphenylacetate (HPCA), is reported at 2.4 A resolution and refined to an R factor of 0.17. Formation of the active site Fe(III). HPCA chelated complex causes the endogenous axial tyrosinate, Tyr447 (147beta), to dissociate from the iron and rotate into an alternative orientation analogous to that previously observed in the anaerobic 3,4-PCD.3,4-dihydroxybenzoate complex (3, 4-PCD.PCA) [Orville, A. M. , Lipscomb, J. D. , & Ohlendorf, D. H. (1997) Biochemistry 36, 10052-10066]. Two orientations of the aromatic ring of HPCA related by an approximate 180 degrees rotation within the active site are consistent with the electron density. Resonance Raman (rR) spectroscopic data from Brevibacteriumfuscum 3,4-PCD.HPCA complex in solution reveals low frequency rR vibrational bands between 500 and 650 cm-1 as well as a band at approximately 1320 cm-1 which are diagnostic of a HPCA. Fe(III) chelate complex. 18O labeling of HPCA at either the C4 or C3 hydroxyl group unambiguously establishes the vibrational coupling modes associated with the five-membered chelate ring system. Analysis of these data suggests that the Fe(III)-HPCAO4 bond is shorter than the Fe(III)-HPCAO3 bond. This consequently favors the model for the crystal structure in which the C3 phenolic function occupies the Fe3+ ligand site opposite the endogenous ligand Tyr408(Oeta) (108beta). This is essentially the same binding orientation as proposed for PCA in the crystal structure of the anaerobic 3,4-PCD.PCA complex based solely on direct modeling of the 2Fo - Fc electron density and suggests that this is the conformation required for catalysis.
Trinucleotide expansions leading to an extended poly‐l‐alanine segment in the poly (A) binding protein PABPN1 cause fibril formation

The nuclear poly(A) binding protein (PABPN1) stimulates poly(A) polymerase and controls the lengths of poly(A) tails during pre‐mRNA processing. The wild‐type protein possesses 10 consecutive Ala residues immediately after the start methionine. Trinucleotide expansions in the coding sequence result in an extension of the Ala stretch to maximal 17 Ala residues in total. Individuals carrying the trinucleotide expansions suffer from oculopharyngeal muscular dystrophy (OPMD). Intranuclear inclusions consisting predominantly of PABPN1 have been recognized as a pathological hallmark of the genetic disorder. To elucidate the molecular events that lead to disease, recombinant PABPN1, and N‐terminal fragments of the protein with varying poly‐l‐alanine stretches were analyzed. As the full‐length protein displayed a strong tendency to aggregate into amorphous deposits, soluble N‐terminal fragments were also studied. Expansion of the poly‐l‐alanine sequence to the maximal length observed in OPMD patients led to an increase of α‐helical structure. Upon prolonged incubation the protein was found in fibrils that showed all characteristics of amyloid‐like fibers. The lag‐phase of fibril formation could be reduced by seeding. Structural analysis of the fibrils indicated antiparallel β‐sheets.
Ensino-aprendizagem da escala de coma de Glasgow: análise de duas técnicas em enfermeiros do serviço de emergência

Partindo do principio de que existe a necessidade de padronizar os enfermeiros quanto a avaliacao do nivel de consciencia, em pacientes atendidos no Servico de Emergencia (SE), utilizando a Escala de Coma de Glasgow (ECGI), questiona-se quais as tecnicas de ensino-aprendizagem mais adequadas. O presente estudo, limitado a medir a aquisicao do conhecimento nessa tematica, teve como objetivos analisar duas tecnicas de ensino-aprendizagem, sendo uma a de exposicao oral com slides e a outra, a leitura dirigida, em enfermeiros que atuam nos SE do municipio de Sao Paulo, divididos em dois grupos, com vistas a: caracteriza-los, segundo algumas variaveis socio-demograficas, de aperfeicoamento profissional e de utilizacao da ECGI; mensurar o grau de conhecimento, utilizando um teste de conhecimentos sobre a ECGI, antes de aplicar as duas tecnicas; verificar o grau de aquisicao de conhecimentos, utilizando o mesmo teste de conhecimentos, apos a aplicacao das duas tecnicas. A coleta de dados foi feita com sorteio previo dos hospitais selecionados quanto a tecnica a ser aplicada e realizada no final de 1999 e inicio de 2000. Os enfermeiros dos hospitais sorteados para serem submetidos a exposicao oral compuseram o Grupo 1 e a leitura dirigida, o Grupo 2. Nas caracteristicas dos dois grupos de enfermeiros, verificaram-se diferencas estatisticamente significativas nas variaveis idade, tempo de formado e utilizacao da ECGI. Os enfermeiros do Grupo 1 eram mais jovens, com faixa etaria predominante entre 22 a 25 anos (45,5 porcento), graduados ha menos de 4 anos (72,7 porcento) e a grande maioria relatou utilizar a ECGI, as vezes (72,7 porcento). Contrariamente, os enfermeiros do Grupo 2 tinham mais de 31 anos (86,3 porcento) e destes, 40,9 porcento, mais que 41 anos; estavam mais distribuidos quanto ao tempo de formado, sendo que mais da metade tinham se graduado ha mais de 5 anos; e, acima de um terco (36,4 porcento) relatou nunca usar a ECGI e 40,9 porcento, as vezes. Homogeneidade nas demais variaveis com preponderância do sexo feminino, e solteiros, graduacao em escolas da Grande Sao Paulo e de tempo de experiencia em SE menor que 5 anos e cursos de educacao continuada variada e baixa, com excecao de Basic Life Support (BLS), frequentado por 45,5 porcento dos enfermeiros do Grupo 1. Na mensuracao do grau de conhecimento previo dos enfermeiros, constatou-se, na totalizacao de pontos, os dois Grupos alcancaram mais de 50 porcento de acertos; aqueles do Grupo 1. (AU)
The Interactive Effects of Exercise and Feeding on Oxygen Uptake, Activity Levels, and Gastric Processing in the Graceful Crab Cancer gracilis

Exercise and digestive processes are known to elevate the metabolic rate of organisms independently. In this study, the effects of simultaneous exercise and digestion were examined in the graceful crab Cancer gracilis. This species exhibited resting oxygen uptake levels between 29 and 42 mg O2 kg−1 h−1. In postprandial crabs, oxygen uptake was approximately double that of unfed crabs. During exercise, oxygen uptake increased three‐ to fourfold, reaching maximal levels of more than 130 mg O2 kg−1 h−1. However, there was no difference in oxygen uptake during activity between unfed and postprandial animals. There was also no difference in exercise endurance levels between unfed and postprandial animals; both sets of animals were unable to right themselves after being turned on their backs, reaching exhaustion after 13–15 attempts. To determine whether increased activity affected gastric processes, the passage of a meal through the digestive system was followed using a fluoroscope. Passage of digesta through the gut system was slower in active animals than in resting crabs. Resting crabs cleared the foregut after approximately 18 h, which was significantly faster than the 34.5 h for constantly active animals. Likewise, the midgut region of resting animals was cleared at a faster rate than that of active animals. Because of residual amounts of digesta remaining in the hindgut, no difference in clearance rates of this section of the gut was evident. The slower clearance times of the foregut were due to a significantly slower rate of mastication of food, as evidenced by a lower cardiac stomach contraction rate. Contraction of the pyloric region of the foregut functions to move the digesta along the midgut, and there was a direct correlation between slower contraction rates of this region and the increased time of passage for digesta through the midgut of active animals. Because increased activity levels affected gastric processing, the crabs exhibited a behavioral response. During a 24‐h period after feeding, there was a significant reduction in locomotor activity. The findings of this study suggest a prioritization of metabolic responses toward activity at the expense of digestion. This is discussed in relation to the ability of the crabs to balance the demands of competing physiological systems.