Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation de cellules épithéliales bronchiques humaines par la GnRH : effet sur le transport ionique médié par le CFTR

Introduction : La mucoviscidose est une maladie genetique autosomale recessive causee par des mutations dans le gene CFTR (cystic fibrosis transmembrane conductance regulator). Ce dernier code un canal chlorure AMPc-dependant localise dans la membrane apicale des cellules epitheliales, dont l’activite est regulee par de nombreuses interactions proteine-proteine. Dans le cadre de la recherche de nouveaux partenaires du CFTR, une interaction directe entre le canal (sauvage et mute F508del) etl’annexine A5 (AnxA5) a ete mise en evidence dans notre laboratoire. Des strategies de sur et de sousexpression nous ont egalement permis d’etablir un lien fonctionnel entre les deux proteines. En effet, nos travaux montrent que les secretions ioniques dependantes du CFTR sont correlees au niveau d’expression intracellulaire de l’AnxA5. Par ailleurs, une elevation des courants medies par le CFTR ainsi qu’une augmentation de la quantite de canaux dans la membrane plasmique sont observees suite a la surexpression de l’AnxA5 dans des cellules exprimant le CFTR mute F508del.But de l’etude : Au vu de ces observations, l’AnxA5 apparait comme une cible potentielle pour la correction de certains defauts engendres par la mutation F508del. Une piste therapeutique pourrait etre l’identification de composes capables d’augmenter son expression dans des cellules epitheliales exprimant le mutant F508del de la proteine CFTR. Considerant les informations fournies par la litterature, notre choix s’est porte sur la GnRH (gonadotropin-releasing hormone), molecule utilisee en therapeutique humaine depuis plus de 25 ans. Ainsi, nous avons evalue l’effet de la GnRH sur la modulation de l’expression de l’AnxA5 et sur le transport ionique dependant du CFTR dans nos differents modeles d’etude Resultats : Outre la presence du recepteur de la GnRH dans nos modeles cellulaires, nous montrons egalement que l’expression de l’AnxA5 y est augmentee des 60 minutes de traitement avec l’hormone (1 nM). De plus, comparativement a des cellules non stimulees, des cellules pretraitees avec la GnRH presentent une hausse significative des sorties actives d’iodure, correlant avec une augmentation de la quantite de CFTR a la surface cellulaire. Ces observations ont ete faites dans les modeles exprimant le CFTR mute F508del ainsi que dans ceux exprimant le CFTR sauvage. Conclusion : Dans nos modeles et selon nos conditions de stimulation, un traitement avec la GnRH augmente l’expression intracellulaire de l’AnxA5 et conduit a une elevation des secretions ioniques mediees par le canal CFTR. Neanmoins, au vu de la multitude de voies de signalisation susceptibles d’etre activees et de genes pouvant etre regules suite a la liaison de la GnRH sur son recepteur, l’effet observe sur l’AnxA5 ne represente probablement pas le seul evenement cellulaire a l’origine de l’impact positif enregistre sur l’activite du canal CFTR.
Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent Pathways

Angiotensin-(1-7) [Ang-(1-7)] causes endothelial-dependent vasodilation mediated, in part, by NO release. However, the molecular mechanisms involved in endothelial NO synthase (eNOS) activation by Ang-(1-7) remain unknown. Using Chinese hamster ovary cells stably transfected with Mas cDNA (Chinese hamster ovary-Mas), we evaluated the underlying mechanisms related to receptor Mas–mediated posttranslational eNOS activation and NO release. We further examined the Ang-(1-7) profile of eNOS activation in human aortic endothelial cells, which constitutively express the Mas receptor. Chinese hamster ovary-Mas cells and human aortic endothelial cell were stimulated with Ang-(1-7; 10−7 mol/L; 1 to 30 minutes) in the absence or presence of A-779 (10−6 mol/L). Additional experiments were performed in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin (10−6 mol/L). Changes in eNOS (at Ser1177/Thr495 residues) and Akt phosphorylation were evaluated by Western blotting. NO release was measured using both the fluorochrome 2,3-diaminonaphthalene and an NO analyzer. Ang-(1-7) significantly stimulated eNOS activation (reciprocal phosphorylation/dephosphorylation at Ser1177/Thr495) and induced a sustained Akt phosphorylation (P<0.05). Concomitantly, a significant increase in NO release was observed (2-fold increase in relation to control). These effects were blocked by A-779. Wortmannin suppressed eNOS activation in both Chinese hamster ovary-Mas and human aortic endothelial cells. Our findings demonstrate that Ang-(1-7), through Mas, stimulates eNOS activation and NO production via Akt-dependent pathways. These novel data highlight the importance of the Ang-(1-7)/Mas axis as a putative regulator of endothelial function.
Mite infestations

Mite infestations are important in dermatology because these may cause dermatologic diseases that range from papulosquamous eruptions to urticarial lesions to bullous eruptions and may spread infectious diseases. These clinical manifestations are important to recognize because mite‐associated diseases may have systemic complications and may be confused with other dermatologic conditions. In treating mite infestations, oral antibiotics may be necessary. Prevention of infestation may be accomplished by pre‐treating clothing with permethrin, using insect repellent N,N‐Diethyl‐meta‐toluamide on clothing and skin, and treating animals infected with mites. This article will review etiology, clinical manifestation, and treatment of mite infestations.
Effect of alum treatment on the concentration of total and ureolytic microorganisms in poultry litter.

Microbial mineralization of urea and uric acid in poultry litter results in the production of ammonia, which can lead to decreased poultry performance, malodorous emissions, and loss of poultry litter value as a fertilizer. Despite the fact that this is a microbial process, little is known about how the microbial populations, especially ammonia-producing (ureolytic) organisms in poultry litter, respond to litter amendments such as aluminum sulfate (Al(2)(SO(4))(3). 14H(2)O; alum). The goal of this study was to measure the temporal changes in total bacterial and fungal populations and urease-producing microorganisms in nontreated litter or litter treated with 10% alum. Quantitative real-time polymerase chain reaction was used to target the bacterial 16S rRNA gene, the fungal 18S rRNA gene, or the urease gene of bacterial and fungal ammonia producers in a poultry litter incubation study. Nontreated poultry litter had relatively high total (2.8 +/- 0.8 x 10(10) cells g(-1) litter) and ureolytic (2.8 +/- 1.3 x 10(8) cells g(-1) litter) bacterial populations. Alum treatment reduced the total bacterial population by 50% and bacterial urease producers by 90% within 4 wk. In contrast, at 16 wk after alum treatment, the fungal population was three orders of magnitude higher in alum-treated litter than in nontreated litter (3.5 +/- 0.8 x 10(7) cells g(-1) litter and 5.5 +/- 2.5 x 10(4) cells g(-1) litter, respectively). The decrease in pH produced by alum treatment is believed to inhibit bacterial populations and favor growth of fungi that may be responsible for the mineralization of organic nitrogen in alum-treated litters.
Heat transfer mathematical modelling in the cooling systems of impure process gases in copper metallurgy

Process gases are high temperature by-products of many processes in copper metallurgy. They are heavily dusted and contain combustible components. The basic element in its treatment system is a post combustion chamber localized directly behind the technological furnace. This chamber permits combusting combustible components and precooling the gases with the aid of cooling water and air. Analysis of the processes occurring in the post combustion chamber is important to reduce the system energy consumption. It requires elaborating a mathematical model which describes the most significant physical and chemical phenomena accompanying the post combustion and cooling. The paper presents a mathematical model of the post combustion and cooling the process gases from an electric furnace in a copper plant. This model was elaborated by means of the CFD (Computational Fluid Dynamics) software (Gambit and Fluent). The k-ε Realizable model of turbulence, a single-stage carbon monoxide combustion model and the DO (Discrete Ordinates) model of radiation were used to build it. Numerical simulations were carried out on the basis of the elaborated model for the maximal mass flow of the process gases form the electric furnace. Exemplary calculation results are presented.
Analysis of the Time—Concentration—Mortality Response of Nilaparvata lugens (Hemiptera: Delphacidae) to Paichongding

ABSTRACT Paichongding is an adicyclicnitromethylene neonicotinoid insecticide with a cis-configuration. Bioassay of paichongding was conducted against Nilaparvata lugens Stål under a laboratory condition. Mortality of N. lugens was analyzed by time—concentration—mortality (TCM) regressions based on the complementary log-log (CLL) model. The conditional mortalities of test individuals increased with the exposure time after treatments with different concentrations, showing that the speed of insecticidal action is concentration dependent. Meanwhile, the conditional mortalities of N. lugens increased as the concentrations of paichongding increased for all developmental stages from instars I-II to macropterous females. Correspondingly, LC50 and LC90 values to N. lugens gradually decreased with the developmental stages, in which instars I-II were the most sensitive to paichongding, with LC50 values of 6.31, 0.45, 0.09, and 0.03 mg/liter for 24, 48, 72, and 96 h after treatments, respectively, while macropterous females were the least sensitive among all developmental stages, with LC50 values of 309.03, 11.48, 1.35, and 0.19 mg/liter at 24, 48, 72, and 96 h after the treatments, respectively. The time—concentration—mortality modeling was mathematically and biologically robust to evaluate the effects of paichongding on N. lugens. The results suggest that paichongding would be an effective alternative pesticide for controlling N. lugens considering its potent effects.
Combination of promoter hypomethylation and PDX1 overexpression leads to TBX15 decrease in vascular IUGR placentas

Preeclampsia (PE) and vascular intra-uterine growth restriction (vIUGR) are two pathological obstetrical conditions originating from placental dysfunction. Recently, methylation changes at the placental level have been shown to be indicative of these diseases. The alteration of such epigenetic marks is therefore a novel pathway that might be critical for these pathologies. Here, we identified a region located in the distal promoter of the T-box-containing transcription factor TBX15 that is differentially methylated in pathological placentas. The level of methylation correlated significantly with the weight and stature of the newborn. The promoter was found to be hypomethylated in vIUGR coinciding with the down-regulation of its expression. PDX1, a transcription factor important for the regulation of insulin metabolism regulation was able to repress the TBX15 promoter in a methylation-dependent manner, which might, at least partially, explain the specific mRNA decrease of TBX15 observed in vIUGR placentas. Overall, the data presented herein suggest that TBX15 might be involved in the pathophysiology of placental diseases.
Human‐directed social behaviour in dogs shows significant heritability

Through domestication and co‐evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human‐directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h2) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human‐directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human‐directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism.
A Novel Thrombomodulin Gene Mutation in a Patient Suffering from Sagittal Sinus Thrombosis

Summary Thrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Öhlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.
Morphodynamic Interpretation of Acute Coronary Thrombosis, with Special Reference to Volcano-Like Eruption of Atheromatous Plaque Caused by Coronary Artery Spasm

Routine autopsy studies of hearts with coronary thrombosis, collected over a period of eleven years, showed unique morphologic features of rup ture of soft atheromatous plaques. These features include: (1) irregular luminar outline: angulation, invagi nation, upheaval, and/or wrinkles, (2) wavy outline of atheromatous cav ity, (3) volcano-like rupture with seepage or gushing of semiliquid ath eromatous contents into lumen, (4) cholesterol crystals arranged in rheo logic vector direction, (5) rupture of deeper intimal fibrous tissue, (6) one or multiple intimal upheavals, (7) fo cal thickening of contracted media, (8) vestige of volcano-like eruption with organized thrombus, and (9) old thrombotic occlusion with wavy ap pearance of thick intimal fibrous tis sue. The authors present a dynamic model of vasoconstriction or artery spasm that accounts for these fea tures and the rupture of soft ather omatous plaques.
Pharmacotherapy Review: Calcium Channel Blockers

As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non‐volume‐dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure‐lowering effect makes them an important component of most multidrug regimens used for blood pressure control.
Stages of competency for medical procedures

Background: Basic medical procedures have historically been taught at the bedside, without a formal curriculum. The supervision of basic procedures is often provided by the next most senior member of the health care team, who themselves may have very little experience. This approach does not allow for preparatory reading or deliberate practise of the procedure, and trainees often track the number of completed procedures as the only evidence of competency, without documented assessments of quality.
Suggested early onset of true action of antidepressant drugs may be artefactual: a heuristic study

In recent decades, there have been many studies reporting that antidepressants have a rapid onset of action, with improvement occurring in the first week. The current pilot study questions whether such findings reflect an artefact emerging from high rates of ‘nonspecific’ improvement and evaluates the phenomenon in a small sample of melancholic patients seemingly lacking nonspecific improvement propensities. Twenty-nine patients with a well-defined melancholic depression completed a 12-week treatment study comparing drug therapy versus cognitive behaviour therapy. The primary outcome measure was the Hamilton Rating Scale for Depression, and a self-report measure of depressed mood severity (the Daily Rating Scale) was completed daily. Analyses seeking time till onset of action were limited to those receiving drug therapies. The lack of improvement in the first 4 weeks for those receiving cognitive behaviour therapy argued for the melancholic patients lacking the capacity for a nonspecific response to therapy. Formal 12-week responder status in those receiving the antidepressant could not be predicted from improvement status until day 12 of the study, and not in the first week as reported in most previous studies of those with major depression. This pilot study argues for any study seeking to quantify the specific interval for onset of action of antidepressant drugs focusing on only those with well-defined melancholia.
Clinical Relevance of Multiple Single-Nucleotide Polymorphisms in Pneumocystis jirovecii Pneumonia: Development of a Multiplex PCR-Single-Base-Extension Methodology

ABSTRACT Pneumocystis jirovecii pneumonia (PcP) is a major cause of respiratory illness in patients with AIDS. The identification of multiple single-nucleotide polymorphisms (SNPs) at three distinct P. jirovecii loci encoding dihydrofolate reductase (DHFR), mitochondrial large-subunit rRNA (mtLSU rRNA), and superoxide dismutase (SOD) was achieved using multiplex-PCR (MPCR) followed by direct sequencing and two single-base extension (SBE) techniques. Four SNPs (DHFR312, mt85, SOD215, and SOD110), correlated previously with parameters of disease, were amplified and genotyped simultaneously. The concordance of results between the standard sequencing technique (direct sequencing) and SBE analysis was 96.9% for the acrylamide gel electrophoresis and 98.4% for the capillary electrophoresis. The cross-genetic analysis established several statistical associations among the SNPs studied: mt85C-SOD110T, SOD110T-SOD215C, and SOD110C-SOD215T. These results were confirmed by cluster analysis. Data showed that among the isolates with low to moderate parasite burden, the highest percentages of DHFR312C, mt85C, SOD110T, and SOD215C were detected, whereas for high parasite burden cases the highest frequencies were observed among isolates with DHFR312T, mt85T, SOD110C, and SOD215T. The polymorphisms studied were shown to be suitable genetic targets potentially correlated with PcP clinical data that can be used as predictors of outcome in further studies to help clinical decision-making in the management of PcP. The MPCR/SBE protocol described for the first time in the present study was shown to be a rapid, highly accurate method for genotyping P. jirovecii SNPs encoded by different loci that could be used for epidemiological studies and as an additional procedure for the prognostic classification and diagnosis of PcP.
Imaginal Feeding for Progression of Diapause Phenotype in the Two-Spotted Spider Mite (Acari: Tetranychidae)

Abstract Adult females of the two-spotted spider mite (Tetranychus urticae Koch) enter diapause under conditions of short-day length and low temperature. A conspicuous body color change, from greenish yellow to bright orange, accompanies diapause induction. This pigmentation is attributed to accumulation of keto-carotenoids produced internally from β-carotene, which is a precursor of vitamin A essential for inducing diapause. The quantity of β-carotene transferred from females to eggs has been considered sufficient to induce diapause. Moreover, carotenoid biosynthesis genes were recently found in this mite. Therefore, imaginal feeding is not likely to be necessary to progress to diapause. In contrast, diapause-induced adult females have been known to feed between the last molt and the time of body color changes. Consequently, the function of imaginal feeding in diapause-induced females was largely unknown. We aimed to clarify whether imaginal feeding was essential to enter diapause. First, we verified that body color change occurred in connection with the feeding behavior, and also verified the change in the composition of carotenoids in diapausing females. Subsequently, we tested the effects of restraints on feeding after molting on carotenoid composition and diapausing rates. Body color change required imaginal feeding. Fed, but not unfed, females accumulated astaxanthin. Moreover, starvation reduced diapausing rates. We concluded that imaginal feeding between the last molt and the time of body color change was necessary to progress to the diapausing phenotype and that starvation at the adult stage reduced the percentage of adults entering reproductive diapause.