Miracle-dz/UniFAR-FTUs huggingface dataset:
RESEARCH Integrative Cardiovascular Physiology and Pathophysiology An in silico simulation of ﬂow-mediated dilation reveals that blood pressure and other factors may inﬂuence the response independent of endothelial function

An in silico simulation of ﬂow-mediated dilation reveals that blood pressure and other factors may inﬂuence the response independent of endothelial function. Am J Physiol Heart Circ Physiol 318: H1337–H1345, 2020. dysfunction is thought to underpin atherosclerotic cardiovascular disease. The most widely used in vivo test of endothelial function is ﬂow-mediated dilation (FMD). However, the results of FMD may be subject to some confounding factors that are not fully understood. We investigated potential biophysical confounding factors that could cause a disassociation between FMD and true endothelial cell shear stress response (the release of endothelium-dependent relaxing factors in response to wall shear stress). Arterial hemodynamics during FMD was simulated using a novel computational modeling approach. The model included an endothelial response function relating changes in wall shear stress to changes in local vascular stiffness in the arm arteries and accounted for vascular stiffening with increasing blood pressure. The hemodynamic effects of cuff inﬂation and deﬂation were modeled by prescribing intraluminal arterial pressure changes and peripheral vasodilation. Evolution of arterial diameter and ﬂow velocity during FMD was assessed by comparison against in vivo data. Our model revealed that vasoconstriction occurring immediately after cuff deﬂation is independent of endothelial response function and entirely caused by the change in transmural pressure along conduit arteries. Moreover, for the same endothelial response function model, FMD values increased exponentially with increasing peak ﬂow velocity, decreased linearly with increasing arterial stiffness at a rate of 0.95%/MPa, and increased linearly with increasing central blood pressure at a rate of 0.22%/mmHg. Dependence of FMD on confounding factors, such as arterial stiffness and blood pressure, suggests that the current FMD test may not reﬂect the true endothelial cell response. NEW & NOTEWORTHY First, a novel computational model simulating arterial hemodynamics during ﬂow-mediated dilation (FMD) was proposed. Second, the model was used to explain why FMD may be inﬂuenced by endothelium-independent factors, showing that FMD results are 1 ) partly masked by the vasoconstriction due to the change in transmural pressure and 2 ) affected by physiological factors (i.e., arterial stiffness and arterial blood pressure) that are difﬁcult to eliminate due to their multiple interactions.
Rôles du frustule des diatomées et des conditions nutritives de leur croissance sur l'export de carbone dans les océans

Dans cette these, deux axes ont ete investigues. Le premier visait a etudier les relations Si-Corg et plus precisement Si-Clipides. La mise au point d’un protocole destine a l’analyse des lipides associes aux frustules a ete realisee. Ce protocole nous a permis de montrer que ces lipides, representant environ 1 % du Corg total, etaient domines par des acides gras satures (14:0, 16:0 et 18:0) chez Thalassiosira weissflogii. Le suivi de cette fraction au cours d’experiences de degradation nous a permis de confirmer l’hypothese de protection de la matiere organique (MO) par la silice biogenique. Ces relations Si-Corg ont egalement ete analysees apres une croissance carencee en nitrate. Les resultats montrent que cette fraction n’etait pas affectee par une carence en nitrate chez T. weissflogii.Notre deuxieme axe d’investigation a consiste a etudier l’impact des conditions nutritives de croissance (carence en N, P et Si) sur la composition biochimique de T. weissflogii et sur sa biodegradation. Le calcul des constantes de degradation de ses differents pools constitutifs (COP, NOP, monosaccharides et lipides) nous a permis de juger de l’efficacite des diatomees carencees, a exporter du Corg. La degradation du Corg est peu affectee par ces carences a l’echelle globale mais sa quantite absolue par cellule augmente. De plus, la reponse physiologique de nos cellules face a une carence en Si semble etre decouplee du metabolisme energetique contrairement aux reponses observees face aux carences en N et P. Cette variabilite de la reponse physiologique pourrait expliquer en partie la variabilite interbassins observee dans les correlations entre flux de Si et de Corg en profondeur.
Radiosensitivity of the helper cell function. [X radiation, mice]

The helper function of T cells primed and irradiated in vivo was tested in vitro by the Mishell-Dutton technique. Spleen cells from mice carrier-primed with HRBC and exposed to 50 to 2000 rads of x-radiation were assayed for their ability to help syngeneic normal spleen cells to mount an in vitro anti-hapten antibody response after stimulation with the conjugate TNP-HRBC. The anti-TNP response was evaluated by the Jerne technique. The helper activity was titrated by adding graded numbers of carrier-primed spleen cells to a constant number of normal spleen cells. The slope of the initial linear portion of the response-cell dose titration curve was taken as an estimate of the helper activity and found to decrease with increasing the x-ray dose. The curve describing the remaining helper activity as a function of the radiation dose shows the presence of two components, one radiosensitive, the other, radioresistant. This suggests the existence either of helper cells at different stages of activation or of two cell subpopulations participating in the helper function.
Chalcone synthase (CHS) family members analysis from eggplant (Solanum melongena L.) in the flavonoid biosynthetic pathway and expression patterns in response to heat stress

Enzymes of the chalcone synthase (CHS) family participate in the synthesis of multiple secondary metabolites in plants, fungi and bacteria. CHS showed a significant correlation with the accumulation patterns of anthocyanin. The peel color, which is primarily determined by the content of anthocyanin, is an economically important trait for eggplants that is affected by heat stress. A total of 7 CHS (SmCHS1-7) putative genes were identified in a genome-wide analysis of eggplants (S. melongena L.). The SmCHS genes were distributed on 7 scaffolds and were classified into 3 clusters. Phylogenetic relationship analysis showed that 73 CHS genes from 7 Solanaceae species were classified into 10 groups. SmCHS5, SmCHS6 and SmCHS7 were continuously down-regulated under 38°C and 45°C treatment, while SmCHS4 was up-regulated under 38°C but showed little change at 45°C in peel. Expression profiles of key anthocyanin biosynthesis gene families showed that the PAL, 4CL and AN11 genes were primarily expressed in all five tissues. The CHI, F3H, F3’5’H, DFR, 3GT and bHLH1 genes were expressed in flower and peel. Under heat stress, the expression level of 52 key genes were reduced. In contrast, the expression patterns of eight key genes similar to SmCHS4 were up-regulated at a treatment of 38°C for 3 hour. Comparative analysis of putative CHS protein evolutionary relationships, cis-regulatory elements, and regulatory networks indicated that SmCHS gene family has a conserved gene structure and functional diversification. SmCHS showed two or more expression patterns, these results of this study may facilitate further research to understand the regulatory mechanism governing peel color in eggplants.
Cobalt ion interaction with TMEM16A calcium-activated chloride channel: Inhibition and potentiation

TMEM16A, a Ca2+-sensitive Cl- channel, plays key roles in many physiological functions related to Cl- transport across lipid membranes. Activation of this channel is mediated via binding intracellular Ca2+ to the channel with a relatively high apparent affinity, roughly in the sub-μM to low μM concentration range. Recently available high-resolution structures of TMEM16 molecules reveal that the high-affinity Ca2+ activation sites are formed by several acidic amino acids, using their negatively charged sidechain carboxylates to coordinate the bound Ca2+. In this study, we examine the interaction of TMEM16A with a divalent cation, Co2+, which by itself cannot activate current in TMEM16A. This divalent cation, however, has two effects when applied intracellularly. It inhibits the Ca2+-induced TMEM16A current by competing with Ca2+ for the aforementioned high-affinity activation sites. In addition, Co2+ also potentiates the Ca2+-induced current with a low affinity. This potentiation effect requires high concentration (mM) of Co2+, similar to our previous findings that high concentrations (mM) of intracellular Ca2+ ([Ca2+]i) can induce more TMEM16A current after the Ca2+-activation sites are saturated by tens of μM [Ca2+]i. The degrees of potentiation by Co2+ and Ca2+ also roughly correlate with each other. Interestingly, mutating a pore residue of TMEM16A, Y589, alters the degree of potentiation in that the smaller the sidechain of the replaced residue, the larger the potentiation induced by divalent cations. We suggest that the Co2+ potentiation and the Ca2+ potentiation share a similar mechanism by increasing Cl- flux through the channel pore, perhaps due to an increase of positive pore potential after the binding of divalent cations to phospholipids in the pore. A smaller sidechain of a pore residue may allow the pore to accommodate more phospholipids, thus enhancing the current potentiation caused by high concentrations of divalent cations.
Ectoparásitos presentes en corzos (Capreolus capreolus) de Galicia (NO España)

Entre abril de 2007 y octubre de 2008, se recogieron 367 pieles de corzo en distintas zonas de Galicia. Las muestras se tomaron 10 mas pronto posible, tras la muerte del animal, para evitar perdida de ectoparasitos; se cuantificaron los ejemplares de cada uno de los estadios de desarrollo (larvas, ninfas y adultos) y se conservaron en alcohol hasta su posterior identificacion. Se encontraron ectoparasitos de tres grupos diferentes: Ixodidae, Mallophaga e Hippoboscidae. En 305 animales (83,1 %) se encontraron garrapatas pertenecientes a la familia Ixodidae, con predominio de la especie Ixodes ricinus (n=305. 83,1%) Y en mucha menor proporcion se identifico Dermacentor marginatus (n=1, 0,3%). La localizacion preferente de las garrapatas fue en las ingles, axilas, region medial de las extremidades y cuello. El unico ejemplar de D. marginatus hallado fue una hembra adulta, mientras que de I. ricinus, se observaron las tres formas de desarrollo, siendo los adultos los mas frecuentes (n=302, 82,3%) y en menor proporcion las ninfas (n=167, 45,5%) y larvas (n=100, 27,2%). La intensidad de infestacion media fue de 43 garrapatas por animal; la mayoria adultos (31 adultos), seguidos de ninfas (17) y larvas (11). La relacion entre hembras y machos fue de 2,94. Ademas, en 12 individuos (3,3%) se hallaron piojos (Mallophaga) de la especie Trichodectes meyeri y dipteros, Hippobosca equina (n= 12, 3,3%) y Lipoptena cervi unicamente en 1 (0,3%) animal.
Working for the future: parentally deprived Nigerian Children have enhanced working memory ability.

BACKGROUND The dominant view based on the deficit model of developmental psychopathology is that early adverse rearing impairs cognition. In contrast, an emerging evolutionary-developmental model argues that individuals exposed to early-life stress may have improved cognitive abilities that are adapted to harsh environments. We set out to test this hypothesis by examining cognitive functions in parentally deprived children in Nigeria. METHODS Cognitive performance was compared between 53 deprived children who currently live in institutional homes and foster families and 51 nondeprived control participants. We used a multifaceted neurocognitive test battery for the assessment of inhibition, set-shifting and working memory. RESULTS Results showed that the deprived and nondeprived group did not significantly differ in their performance on set-shifting and inhibition tasks. Conversely, the deprived group performed significantly better than the nondeprived group in the working memory task. DISCUSSION We interpret the enhanced working memory ability of the deprived group as a correlate of its ecological relevance. In Nigeria, underprivileged children may need to rely to a larger extent on working memory abilities to attain success through academic work. This study provides further evidence that exposure to early adversity does not necessarily impair cognitive functions but can even enhance it under some conditions and in some domains.
Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague‐Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short‐ and long‐term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p < . 001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long‐term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p = . 0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox‐42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p < .0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus.
Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro

Significance The incidence of infections due to fungal pathogens has dramatically increased in human populations with weakened or suppressed immune systems. Understanding how organisms rapidly adapt during human infection to enhance virulence and evolve drug resistance is important for developing effective treatments. We find that transposon mobilization in the human pathogen Cryptococcus causes genomic mutations in a murine model of infection and promotes resistance to antifungal drugs in vitro. Thermotolerance is a key virulence determinant for pathogenic fungi during the environment-to-host transition, and we demonstrate that a temperature increase is sufficient to trigger transposon mobilization in vitro. The link between temperature stress and transposon-associated mutations may significantly impact adaptation to the host during infection, including the acquisition of drug resistance. When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these microbes are not well adapted human pathogens. Cryptococcus species are yeastlike fungi that cause lethal infections, especially in HIV-infected patients. Using Cryptococcus deneoformans in a murine model of infection, we examined contributors to drug resistance and demonstrated that transposon mutagenesis drives the development of 5-fluoroorotic acid (5FOA) resistance. Inactivation of target genes URA3 or URA5 primarily reflected the insertion of two transposable elements (TEs): the T1 DNA transposon and the TCN12 retrotransposon. Consistent with in vivo results, increased rates of mutagenesis and resistance to 5FOA and the antifungal drugs rapamycin/FK506 (rap/FK506) and 5-fluorocytosine (5FC) were found when Cryptococcus was incubated at 37° compared to 30° in vitro, a condition that mimics the temperature shift that occurs during the environment-to-host transition. Inactivation of the RNA interference (RNAi) pathway, which suppresses TE movement in many organisms, was not sufficient to elevate TE movement at 30° to the level observed at 37°. We propose that temperature-dependent TE mobilization in Cryptococcus is an important mechanism that enhances microbial adaptation and promotes pathogenesis and drug resistance in the human host.
G0S2, an early response gene, regulates quiescence in naïve T cells (104.10)

The G0/G1 switch gene 2 (G0S2) was identified in a screen using mitogen-activated human blood mononuclear cells (DNA and Cell Biology 9, 579, 1990). G0S2 is a small basic protein expressed in hematopoietic cells that is upregulated in autoimmune and inflammatory processes. However, the ability of G0S2 to control T cell proliferation has yet to be determined. We found that G0S2 transcription was suppressed following TCR activation in naïve T cells, suggesting its role in T cell quiescence. Also, inhibition of MAPK, PI3K, mTOR and Ca2+/calcineurin pathways abrogated G0S2 gene suppression, which suggests that the aforementioned pathways are involved in the suppression of G0S2. Moreover, gain-of function experiments, using retroviral gene transfer and BM transplantation, showed that ectopic G0S2 expression inhibited proliferation of T cells during homeostasis and upon TCR activation. Conversely, silencing G0S2 expression enhanced T cell proliferation, indicating that G0S2 maintains quiescence of naïve T cells. We further identified nucleolin as a protein partner of G0S2 by Co-IP and mass-spectrometry. This data suggests that G0S2 interferes with nucleolin-mediated stabilization of mRNAs of genes required for proliferation control. Collectively, our study uncovered an important role of G0S2 in the mechanism of T cell quiescence.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease

North Bristol Lung Centre, Southmead Hospital, Bristol, UK Respiratory, Wye Valley NHS Trust, Hereford, UK Centre for Medical Education, Queens University Belfast, Regional Respiratory Centre, Belfast City Hospital, Belfast, UK Medical Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Cardiovascular and Respiratory Studies, Hull York Medical School/University of Hull, Hull, UK Institute of Biomedical and Clinical Science, College of Medicine & Health, University of Exeter, Exeter, UK Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK Oxford Respiratory Trials Unit and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK Pharmacy, University College London Hospitals NHS Foundation Trust, London, UK
R‐DHA‐oxaliplatin (R‐DHAOx) versus R‐DHA‐cisplatin (R‐DHAP) regimen in B‐cell lymphoma treatment: A eight‐year trajectory study

The R‐DHAP regimen (rituximab, cisplatin, dexamethasone, and high‐dose cytarabine) is standardly used to treat relapsed Non‐Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R‐DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine‐based trajectory modeling.
Effect of Mn-substitution on impedance spectroscopy and magnetic properties of Al-doped ZnO nanoparticles

In this study, the role of Mn-substitution on the structural, morphological, dielectric, and magnetic properties of Al-doped ZnO nanoparticles has been examined, using XRD, FE-SEM, μAutolab/FRA2 impedance spectroscopy, and vibrating sample magnetometer (VSM) techniques. Structural investigations revealed diffraction peaks consistent with JCPDS card No. 036–1451. Morphological evaluations of the synthesized nanoparticles indicated that the shape of the nanoparticles is a slightly hexagonal and generally spherical structure with a size range of approximately 10–70 nm. Dielectric measurements were performed in frequency ranges between 10−3 Hz and 1 MHz. The results show that the sample's dielectric behavior is affected both by crystallite size and doping material type. In addition, it can be observed that the dielectric parameters exhibit extreme frequency dependence. Mn-substituted Al-doped ZnO is a suitable candidate for high-frequency applications due to its low dielectric loss at high frequencies. The AC conductivity of the Mn-substituted Al-doped ZnO sample increases with each frequency increment, and its value is higher than for the Al-doped ZnO sample, makings it a desirable material for use in device applications. Magnetic calculations, extracted from dielectric impedance spectroscopy measurements, are also investigated. Complex magnetic permeability, together with magnetic loss curves, are also plotted. Finallly, a study of the magnetic properties of the sample, using VSM, showed room-temperature ferromagnetic behavior.