1,084 research outputs found

    Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

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    Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

    Position as an independent variable and the emergence of the 1/21/2-time fractional derivative in quantum mechanics

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    Using the position as an independent variable, and time as the dependent variable, we derive the function P(±){\cal P}^{(\pm)}, which generates the space evolution under the potential V(q){\cal V}(q) and Hamiltonian H{\cal H}. Canonically conjugated variables are the time and minus the Hamiltonian. While the classical dynamics do not change, the corresponding quantum operator naturally leads to a 1/21/2-fractional time evolution, consistent with a recently proposed spacetime symmetric formalism of quantum mechanics. Using Dirac's procedure, separation of variables is possible, and while the coupled position-independent Dirac equations depend on the 1/21/2-fractional derivative, the coupled time-independent Dirac equations (TIDE) lead to positive and negative shifts in the potential, proportional to the force. Both equations couple the (±\pm) solutions of P^(±){\cal \hat P}^{(\pm)} and the kinetic energy K0{\cal K}_0 is the coupling strength. We obtain a pair of coupled states for systems with finite forces. The potential shifts for the harmonic oscillator (HO) are ±ω/2\pm\hbar\omega/2, and the corresponding pair of states are coupled for K00{\cal K}_0\ne 0. No time evolution is present for K0=0{\cal K}_0=0, and the ground state with energy ω/2\hbar\omega/2 is stable. For K0>0{\cal K}_0>0, the ground state becomes coupled to the state with energy ω/2-\hbar\omega/2, and \textit{this coupling} allows to describe higher excited states. Energy quantization of the HO leads to quantization of K0=kω{\cal K}_0=k\hbar\omega (k=1,2,k=1,2,\ldots). For the one-dimensional Hydrogen atom, the potential shifts become imaginary and position-dependent. Decoupled case K0=0{\cal K}_0=0 leads to plane-waves-like solutions at the threshold. Above the threshold, we obtain a plane-wave-like solution, and for the bounded states the wave-function becomes similar to the exact solutions but squeezed closer to the nucleus.Comment: 11 pages, 6 figure

    Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

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    Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

    Fractional integrodifferential equations and (anti-)hermiticity of time in a spacetime-symmetric extension of nonrelativistic Quantum Mechanics

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    Time continues to be an intriguing physical property in the modern era. On the one hand, we have the Classical and Relativistic notion of time, where space and time have the same hierarchy, which is essential in describing events in spacetime. On the other hand, in Quantum Mechanics, time appears as a classical parameter, meaning that it does not have an uncertainty relation with its canonical conjugate. In this work, we use a recent proposed spacetime-symmetric formalism~\href{https://doi.org/10.1103/PhysRevA.95.032133}{[Phys.~Rev.~A {\bf 95}, 032133 (2017)]} that tries to solve the unbalance in nonrelativistic Quantum Mechanics by extending the usual Hilbert space. The time parameter tt and the position operator X^\hat{X} in one subspace, and the position parameter xx and time operator T\mathbb{T} in the other subspace. Time as an operator is better suitable for describing tunnelling processes. We then solve the novel 1/21/2-fractional integrodifferential equation for a particle subjected to strong and weak potential limits and obtain an analytical expression for the tunnelling time through a rectangular barrier. We compare to previous works, obtaining pure imaginary times for energies below the barrier and a fast-decaying imaginary part for energies above the barrier, indicating the anti-hermiticity of the time operator for tunnelling times. We also show that the expected time of arrival in the tunnelling problem has the form of an energy average of the classical times of arrival plus a quantum contribution.Comment: 11 pages, 3 figure

    How Mistimed and Unwanted Pregnancies Affect Timing of Antenatal Care Initiation in three Districts in Tanzania

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    Early antenatal care (ANC) initiation is a doorway to early detection and management of potential complications associated with pregnancy. Although the literature reports various factors associated with ANC initiation such as parity and age, pregnancy intentions is yet to be recognized as a possible predictor of timing of ANC initiation. Data originate from a cross-sectional household survey on health behaviour and service utilization patterns. The survey was conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania on 910 women of reproductive age who had given birth in the past two years. ANC initiation was considered to be early only if it occurred in the first trimester of pregnancy gestation. A recently completed pregnancy was defined as mistimed if a woman wanted it later, and if she did not want it at all the pregnancy was termed as unwanted. Chisquare was used to test for associations and multinomial logistic regression was conducted to examine how mistimed and unwanted pregnancies affect timing of ANC initiation. Although 49.3% of the women intended to become pregnant, 50.7% (34.9% mistimed and 15.8% unwanted) became pregnant unintentionally. While ANC initiation in the 1st trimester was 18.5%, so was 71.7% and 9.9% in the 2nd and 3rd trimesters respectively. Multivariate analysis revealed that ANC initiation in the 2nd trimester was 1.68 (95% CI 1.10‒2.58) and 2.00 (95% CI 1.05‒3.82) times more likely for mistimed and unwanted pregnancies respectively compared to intended pregnancies. These estimates rose to 2.81 (95% CI 1.41‒5.59) and 4.10 (95% CI 1.68‒10.00) respectively in the 3rd trimester. We controlled for gravidity, age, education, household wealth, marital status, religion, district of residence and travel time to a health facility. Late ANC initiation is a significant maternal and child health consequence of mistimed and unwanted pregnancies in Tanzania. Women should be empowered to delay or avoid pregnancies whenever they need to do so. Appropriate counseling to women, especially those who happen to conceive unintentionally is needed to minimize the possibility of delaying ANC initiation.\u

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

    Normative data on regional sweat-sodium concentrations of professional male team-sport athletes

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    Background: The purpose of this paper was to report normative data on regional sweat sweat-sodium concentrations of various professional male team-sport athletes, and to compare sweat-sodium concentrations among sports. Data to this effect would inform our understanding of athlete sodium requirements, thus allowing for the individualisation of sodium replacement strategies. Accordingly, data from 696 athletes (Soccer, n = 270; Rugby, n = 181; Baseball, n = 133; American Football, n = 60; Basketball, n = 52) were compiled for a retrospective analysis. Regional sweat-sodium concentrations were collected using the pilocarpine iontophoresis method, and compared to self-reported measures collected via questionnaire. Results: Sweat-sodium concentrations were significantly higher (p < 0.05) in American football (50.4 ± 15.3 mmol·L-1), baseball (54.0 ± 14.0 mmol·L-1), and basketball (48.3 ± 14.0 mmol·L-1) than either soccer (43.2 ± 12.0 mmol·L-1) or rugby (44.0 ± 12.1 mmol·L-1), but with no differences among the N.American or British sports. There were strong positive correlations between sweat-sodium concentrations and self-reported sodium losses in American football (rs = 0.962, p < 0.001), basketball (rs = 0.953, p < 0.001), rugby (rs = 0.813, p < 0.001), and soccer (rs = 0.748, p < 0.001). Conclusions: The normative data provided on sweat-sodium concentrations might assist sports science/medicine practitioners in generating bespoke hydration and electrolyte-replacement strategies to meet the sodium demands of professional team-sport athletes. Moreover, these novel data suggest that self-reported measures of sodium loss might serve as an effective surrogate in the absence of direct measures; i.e., those which are more expensive or non-readily available

    Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 Loci

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    Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation) are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA) gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449) that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility

    SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

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    Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org
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