Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular ADP Modulates the Ca Release-activated Ca Current in a Temperature- and Ca-dependent Way (*)

The rat basophilic cell line RBL-1 is known to express high levels of the Ca current activated by store depletion, known as Ca release-activated Ca current (I), the main Ca influx pathway so far identified in nonexcitable cells. We show here that, as reported in other cell types, metabolic drugs strongly inhibit the Ca influx operated by store depletion in RBL-1 cells also. We have tested the hypothesis that intracellular adenine and/or guanine nucleotide levels act as coupling factors between I and cell metabolism. Using the whole cell configuration of the patch-clamp technique, we demonstrate that addition of ADP to the intracellular solution significantly reduces I induced by inositol 1,4,5-trisphosphate. This phenomenon differs from other regulatory pathways of I, since it is highly temperature-dependent, is observable only in the presence of low intracellular Ca buffering capacity, and requires a cytosolic factor(s) which is rapidly lost during cell dialysis. Moreover, the inhibition is specific for ADP and is partially mimicked by ADPβS and AMP, but not by GDP or GTP.
Modeling TCP performance over wireless channels using fixed-point approximation

Wireless channels are prone to transmission errors. Loss of IP packets due to imperfect local error concealment strategy implemented at the data-link layer is the major reason for TCP performance degradation in wireless networks. These losses are misinterpreted by TCP senders as congestion indications and subsequently lead to decrease of the sending rate. In addition to wireless losses IP packets can also be lost due to buffer overflow at the IP layer. To study performance experienced by a number of concurrent TCP sessions sharing the same wireless bottleneck we adopt the fixed-point approach. We demonstrate that throughput provided to TCP flows is complex cross-layer function depending on wireless channel statistics and configuration of the protocol stack at the wireless interface.
Round window electrode insertion potentiates retention in the scala tympani

Abstract Conclusions: The round window membrane (RWM)-intentioned approach is superior to the traditional bony cochleostomy (BC) approach in obtaining electrode placement within the scala tympani (ST). Objective: Cochlear implant outcome is influenced by several factors, including optimal placement and retention of the electrode array within the ST. The present study aimed to assess whether the RWM route is superior to a traditional BC for placement and retention of the electrode array in the ST. Methods: This was a prospective consecutive non-randomized comparison study. All patients were implanted with the Advanced Bionics 1J electrode array. The RWM approach (n = 32) was compared with a traditional BC group (n = 33). The outcome measure was the electrode position as judged within the scalar chambers at four points along the basal turn using postoperative computed tomography (CT). Results: When the mean position scores were compared, the RWM-intentioned group had significantly more electrodes directed towards the ST compartment than the BC group (p < 0.001). The RWM electrodes achieved 94% ST retention compared with 64% for the BC group (p < 0.05). All electrodes stayed in the ST in the RWM group, whereas in the BC group 9% crossed from the ST to the scala vestibuli.
Enantioselective Total Synthesis of (+)-Lyngbyabellin M

Lyngbyabellin M is a non-ribosomal peptide synthetase/polyketide synthase derived metabolite isolated from the cyanobacterium M. bouillonii displaying thiazole rings and a distinct chlorinated octanoic acid chain. Its absolute configuration was proposed based on the comparison of its spectroscopic data with those of other representatives of this family of marine natural products, as well as degradation and derivatization studies. Here the first total synthesis of (+)-lyngbyabellin M is described based on the coupling of three key intermediates: two chiral thiazole moieties and an anti hydroxycarboxylic acid prepared stereoselectively via a boron enolate mediated aldol reaction directed by Masamune’s chiral auxiliary.
Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

BACKGROUND/AIMS Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population. MATERIALS AND METHODS Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohn's disease patients, 157 ulcerative colitis patients, and 89 healthy controls. RESULTS The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohn's disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohn's disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohn's disease. The presence of rs10758669 (AC) was protective against perianal Crohn's disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohn's disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohn's disease and rs11209026 in ulcerative colitis were associated with disease-related operation. CONCLUSION This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.
γ-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase

ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by γ-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. γ-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of γ-secretase also prevented growth inhibition by HRG. γ-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase–mediated signaling.
True or False? The Hygiene Hypothesis for Crohn's Disease

The “hygiene hypothesis” for Crohn's disease postulates that multiple childhood exposures to enteric pathogens protect an individual from developing Crohn's disease later in life, while individuals raised in a more sanitary environment are more likely to develop Crohn's disease. In this issue of the American Journal of Gastroenterology, two Canadian case-control studies come to diametrically opposed conclusions regarding the hygiene hypothesis for Crohn's disease. This difference may be partially related to differences in study population (population based vs hospital based), age of onset, different genetic determinants, urban/rural residence (40% rural vs principally urban), or different exposures from the putative causative agent. As of now, the veracity of the hygiene hypothesis for Crohn's disease is not confirmed.
The effects of methadone and its role in fatalities

Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. Such use of the drug has increased as its advantages have become widely recognized. There are undesirable outcomes from its greater use, including a substantial market in diverted methadone and a high number of deaths where the drug has been implicated. It is important to understand how and why methadone causes death so that such fatalities can be minimized, and to disseminate such information. This paper presents an overview of the chief effects of methadone on the human body, considering its metabolism, drug interactions and tolerance. The principal mechanisms by which methadone causes death are discussed: respiratory depression, aspiration of vomit, pulmonary oedema, bronchopneumonia, cardiac problems and renal failure. Many such deaths are preventable, if drug interactions and polydrug use are avoided, its longer period of metabolism and individuals' tolerance levels are considered. It is hoped that this paper will (a) help guide health professionals in their management and treatment of patients participating in methadone treatment programmes, and (b) provide some basic information for those dealing with individuals who have consumed methadone. Copyright © 2004 John Wiley & Sons, Ltd.
Microlevel determinants of blood pressure among women of two ethnic groups in a periurban area of Kolkata city, India

Blood pressure (BP) trends vary cross‐culturally, and studies on the risk factors associated with hypertension are limited in periurban regions of India. This study was conducted to examine the effect of socioeconomic factors (income, expenditure, activity time) and anthropometric measurements (skinfolds of biceps, triceps, subscapular, supra iliac, and body mass index) on 102 Munda (tribe) and 135 Pod (caste) women of childbearing age in a periurban area of Kolkata city. Results indicate that Munda women had significantly higher diastolic BP in the 30+ age group. However, no difference in the systolic and diastolic BP was observed between the two groups, when the socioanthropometric factors were controlled as covariates. Also, according to the JNC (JNC, 2004, The JNC 7 Report NIH Publication No. 04‐5230) classification of hypertension, no significant difference in hypertension was noted between the women of the two social groups. But the risk factors associated with hypertension varied between the two ethnic groups. Expenditure on alcohol and activity time was associated with hypertension among the Munda, while body mass index was significantly associated with hypertension among the Pod women. Alcohol consumption is a rare phenomenon among Indian women. Yet, Munda women in this transitional periurban environment, in spite of high poverty were more inclined to spent their earnings in alcohol consumption (due to their cultural preferences), increasing the risk of hypertension in their childbearing age.Am. J. Hum. Biol. 19:409–415, 2007. © 2007 Wiley‐Liss, Inc.
Chondrichthyans have a bulbus arteriosus at the arterial pole of the heart: morphological and evolutionary implications

It has been generally assumed that the outflow tract of the chondrichthyan heart consists of the conus arteriosus, characterized by cardiac muscle in its walls. However, classical observations, neglected for many years, indicated that the distal component of the cardiac outflow tract of several elasmobranch species was composed of tissue resembling that of the ventral aorta. The present study was outlined to test the hypothesis that this intrapericardial, non‐myocardial component might be homologous to the actinopterygian bulbus arteriosus. The material consisted of Atlantic catshark adults and embryos, which were examined by means of histochemical and immunohistochemical techniques for light and fluorescence microscopy. In this species, the distal component of the outflow tract differs histomorphologically from both the ventral aorta and the conus arteriosus; it is devoid of myocardium, is covered by epicardium and is crossed by the coronary arterial trunks. In the embryonic hearts examined, this distal component showed positive reactivity for 4,5‐diaminofluorescein 2‐diacetate (DAF‐2DA), a fluorescent nitric oxide indicator. These findings, together with other observations in holocephals and several elasmobranch species, confirm that chondrichthyans possess a bulbus arteriosus interposed between the conus arteriosus and the ventral aorta. Therefore, the primitive heart of gnathostomates consists of five intrapericardial components, sinus venosus, atrium, ventricle, conus arteriosus and bulbus arteriosus, indicating that the bulbus arteriosus can no longer be regarded as an actinopterygian apomorphy. The DAF‐2DA‐positive reactivity of the chondrichthyan embryonic bulbus suggests that this structure is homologous to the base of the great arterial trunks of birds and mammals, which derives from the embryonic secondary heart field.
Intrinsically disordered inhibitor of glutamine synthetase is a functional protein with random‐coil‐like pKa values

The sequential action of glutamine synthetase (GS) and glutamate synthase (GOGAT) in cyanobacteria allows the incorporation of ammonium into carbon skeletons. In the cyanobacterium Synechocystis sp. PCC 6803, the activity of GS is modulated by the interaction with proteins, which include a 65‐residue‐long intrinsically disordered protein (IDP), the inactivating factor IF7. This interaction is regulated by the presence of charged residues in both IF7 and GS. To understand how charged amino acids can affect the binding of an IDP with its target and to provide clues on electrostatic interactions in disordered states of proteins, we measured the pKa values of all IF7 acidic groups (Glu32, Glu36, Glu38, Asp40, Asp58, and Ser65, the backbone C‐terminus) at 100 mM NaCl concentration, by using NMR spectroscopy. We also obtained solution structures of IF7 through molecular dynamics simulation, validated them on the basis of previous experiments, and used them to obtain theoretical estimates of the pKa values. Titration values for the two Asp and three Glu residues of IF7 were similar to those reported for random‐coil models, suggesting the lack of electrostatic interactions around these residues. Furthermore, our results suggest the presence of helical structure at the N‐terminus of the protein and of conformational changes at acidic pH values. The overall experimental and in silico findings suggest that local interactions and conformational equilibria do not play a role in determining the electrostatic features of the acidic residues of IF7.
The PON1192RR genotype is associated with a higher prevalence of arterial hypertension

Objective To investigate whether genetic polymorphism of paraoxonase (PON1192), an enzyme which protects low density lipoprotein from oxidation, is related to the prevalence of arterial hypertension. Methods Two groups of carefully selected subjects of both sexes were enrolled and compared. The first group comprised 219 healthy controls (mean age 46.5 ± 14.7 years) whereas the second comprised 119 hypertensive patients (mean age 47.9 ± 10.5 years) with untreated essential arterial hypertension. Anthropometric and biochemical parameters were within the normal range in both groups. The PON1192 polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism approach. Results In hypertensive patients, a significant increase of the frequency of PON1192RR genotype with respect to healthy controls (14.3 versus 5.0%, P = 0.003) was found. Logistic regression analyses also showed that the PON1192RR genotype was independently associated with a four-fold increase in susceptibility to arterial hypertension (odds ratio = 4.31; 95% confidence interval = 1.63–11.43, P = 0.003). Conclusions The finding that PON1192RR genotype is associated with a higher prevalence of arterial hypertension may contribute to improving the stratification of cardiovascular risk within a population aged 30–60 years. Determination of the PON1192 polymorphism may help to identify those individuals who are prone to developing cardiovascular diseases at an early stage, suggesting the need for close monitoring of cardiovascular risk factors before the onset of cardiovascular disease.
Methodological Issues Encountered in a Study of Hospitalized COPD Patients

A study with hospitalized chronic obstructive pulmonary disease (COPD) patients determined the feasibility of providing and evaluating a tailored education program. This article describes two methodological issues encountered. Issues included recruitment and retention, and selection of outcome measures. The COPD Self-Efficacy Scale (CSES) and Dartmouth Functional Health Status (FHS) charts provided data on evaluation and outcome measurements. Of 67 patients, 55% met eligibility criteria, 73% (n = 27) agreed to participate, and 74% (n = 20) completed the study. Results revealed acceptance and satisfaction with the educational intervention. The median CSES score, significantly (z = 3.51,p = .004) improved from 53% to 82%. In FHS, a 20% improvement occurred in all except social support. Methodological concerns with the CSES reinforced the need for further investigation of the reliability and validity for hospitalized COPD patients. Researchers’ observations may assist in planning educational interventions and program evaluations with hospitalized COPD patients.
Effect of diet composition on renal morphology in diabetic rats.

Streptozotocin-induced diabetic rats were fed rodent diets with standard (4.5%) or high (10%) polyunsaturated fatty acid content for up to 12 months. Diabetic rats fed a standard diet developed thickening of glomerular basement membrane (GBM) when compared to similarly fed controls (285 +/- 21 vs. 243 +/- 18 nm, respectively; p = 0.0003). No differences in GBM thickening were observed between control and diabetic rats fed high-fat diets (188 +/- 23 vs. 195 +/- 21 nm, respectively; p = n.s.). Regardless of diabetes, all rats fed high polyunsaturated fat diets had decreased GBM thickness compared to standard-fed rats (p = 0.0001). Glomerular and mesangial volumes were similar in control and diabetic rats fed standard or high fat diets. Diets high in polyunsaturated fatty acids prevent GBM thickening in diabetes and reduce GBM thickness in control rats.
Extrêmes hydro-météorologiques et exposition sur les routes : Contribution à MobRISK : modèle de simulation de l'exposition des mobilités quotidiennes aux crues rapides

Les crues rapides sont considerees parmi les catastrophes naturelles les plus dangereuses en raison de leur imprevisibilite et la rapidite de leurs dynamiques spatio-temporelles. Meme si ces evenements touchent generalement des petites etendues spatiales, elles causent un nombre important de victimes. Les differentes analyses des impacts des crues rapides pointent la mo- bilite quotidienne comme un facteur principal augmentant l’exposition et la vulnerabilite des individus : pres de la moitie des victimes sont des automobilistes surpris par les submersions des routes durant leurs trajets quotidiens. C’est dans ce contexte que plusieurs travaux ont ete conduits afin de developper des outils de prevision des coupures des routes par submersion dans le departement du Gard, frequemment expose a des evenements hydro-meteorologiques extremes. Ces etudes ont permis d’identifier les points de coupure, situes aux niveaux des intersections routes/rivieres, vulnerables aux crues rapides et de developper des methodes d’estimation du risque de submersion des routes.Cette these s’inscrit dans la continuite de ces travaux dans le but de quantifier et de caracteriser l’exposition des individus aux crues rapides durant leurs mobilites. Pour cela, nous avons contribue au developpement de MobRISK : un modele de simulation de l’ex- position des automobilistes aux submersions des routes lors d’evenements de crues rapides. Une premiere application de MobRISK est presentee dans le but d’evaluer l’exposition d’une population d’un zone d’etude, situee au nord-ouest du Gard, a l’evenement de crue rapide des 8-9 Septembre 2002.Les resultats de ce cas d’etude ont permis d’identifier un decalage entre les dynamiques temporelles du trafic simule au niveau des points de coupure et des niveaux de submersion de ces points. Ce decalage temporel a probablement constitue un facteur de reduction du nombre de victimes sur la route. La combinaison des estimations de submersion des routes avec le trafic simule a permis de localiser les routes qui ont presente le plus de danger pour les automobilistes lors de cet evenement. Ensuite, l’evaluation de l’exposition individuelle aux submersions routieres a permis d’identifier les profils socio-demographiques des automobilistes les plus exposes constitues majoritairement de jeunes actifs de sexe masculin.Enfin, differents scenarios de comportements en situation de crise ont ete construits et tes- tes a travers l’integration des decisions d’adaptation des deplacements face aux perturbations environnementales. La comparaison des effets des scenarios de comportements a permis de souligner le role important des regles adoptees dans les prises de decision et dans l’evaluation du danger dans la reduction l’exposition des automobilistes.Au final, cette these souligne les potentialites et les performances de MobRISK comme un outil innovant et prometteur pour la simulation de l’exposition sociale aux crues.
A New Primer for Sex Identification of Ducks and a Minimally Invasive Technique for Sampling of Allantoic Fluid to Detect Sex during Bird Embryo Development

During the early incubation period of the duck, from embryonic day 1 to 13, a precise identification of the sex may be difficult. In a preliminary test, we found a defect in the use of the classical P2/P8, 1237L/1272H, and 2550F/2718R primers for chromo-helicase-DNA-binding 1 gene (CHD1) as a PCR-based test to identify sex in ducks. Therefore, universal PCR primers HPF/HPR for sexing ducks were designed. The PCR product was cloned, sequenced, and analyzed using GenBank. The effectiveness of the primers was compared using samples of blood and feathers from adult birds and chorioallantoic membranes and allantoic fluid (AF) of embryos as a source of DNA. The 495-bp CHD1-Z and the 351-bp CHD1-W PCR amplicons could be easily distinguished on a 3% agarose gel, and females (ZW) displayed 2 visible bands whereas only a single band was found in males (ZZ). The results indicated that HPF/HPR primers were highly efficient and more reliable than the classical primers used for sexing ducks. During the design of the new primers, an AF sampling technique was established to collect a very small amount of AF from free-living birds. This technique, which was minimally invasive, had no adverse effects on either embryos or the post-hatching survival of young ducks and could be used in developmental biology research in birds.
Does Sophistication of the Weighting Scheme Enhance the Performance of Long-Short Commodity Portfolios?

The article develops a long-short portfolio construction technique that captures the fundamentals of backwardation and contango present in commodity futures markets and simultaneously deviates from the equal-weighting scheme traditionally employed in the literature. The sophisticated weighting schemes based on risk minimization and risk timing are found to dominate the traditional naive allocation and the schemes based on utility maximization. The conclusion applies to both momentum and term structure portfolios and persists after accounting for transaction costs, lack of liquidity, various model specifications, and different sub-periods.