Pacing with restoration of respiratory sinus arrhythmia improved cardiac contractility and the left ventricular output: a translational study

Introduction: Respiratory sinus arrhythmia (RSA) is a prognostic value for patients with heart failure and is defined as a beat-to-beat variation of the timing between the heart beats. Patients with heart failure or patients with permanent cardiac pacing might benefit from restoration of RSA. The aim of this translational, proof-of-principle study was to evaluate the effect of pacing with or without restored RSAon parameters of LV cardiac contractility and the cardiac output

Increased cardiac output and left ventricular contractility in pigs paced with vs. without restored respiratory sinus arrhythmia - proof of principle of a newly developed pacing device

Heart rate variability (HRV) correlates with the severity and mortality of heart failure. Respiratory sinus arrhythmia (RSA) is defined by the dynamic increase and decrease in heart rate between breaths. Restoration of RSA might be beneficial in patients with heart failure and/or patients in need of permanent pacing. The aim of this translational, proof-of-principle study was to investigate the effect of pacing with or without RSA using a newly designed pacing device on the left ventricular contractility and cardiac output

Solar-like oscillations in the G2 subgiant beta Hydri from dual-site observations

We have observed oscillations in the nearby G2 subgiant star beta Hyi using high-precision velocity observations obtained over more than a week with the HARPS and UCLES spectrographs. The oscillation frequencies show a regular comb structure, as expected for solar-like oscillations, but with several l=1 modes being strongly affected by avoided crossings. The data, combined with those we obtained five years earlier, allow us to identify 28 oscillation modes. By scaling the large frequency separation from the Sun, we measure the mean density of beta Hyi to an accuracy of 0.6%. The amplitudes of the oscillations are about 2.5 times solar and the mode lifetime is 2.3 d. A detailed comparison of the mixed l=1 modes with theoretical models should allow a precise estimate of the age of the star.Comment: 13 pages, 14 figures, accepted by ApJ. Fixed minor typo (ref to Fig 14

Molecular and phenotypic diversity among chickpea (Cicer arietinum) genotypes as a function of drought tolerance

Diversity as a function of drought tolerance may be identified by morphological characters, and molecular tools used to find the most divergent genotypes for breeding programs for drought tolerance in future. The narrow genetic base of chickpea can be circumvented by using diverse lines in breeding programs. Forty chickpea genotypes were studied for their morphological and molecular diversity with an objective of identifying the most diverse drought-tolerant lines. In total, 90 alleles were detected with 3.6 alleles per locus. Polymorphism information content (PIC) values ranged from 0.155 to 0.782 with an average value of 0.4374 per locus. The size of amplified products ranged from 160 bp to 390 bp. Primer TA136 with eight alleles showed the highest PIC value of 0.7825, indicating its ability to differentiate the genotypes at molecular level. DARwin neighbour-joining tree analysis based on dissimilarity estimates was done for the molecular data and sequential agglomerative hierarchical non-overlapping (SAHN) grouping for the morphological data. It could clearly discriminate the tolerance and the sensitivity of genotypes. Two-dimensional principal coordinates analysis (PCoA) plot indicated good diversity for drought tolerance. The genetic similarity coefficients ranged from 0.115 (genotypes BGD72 to ICCV 5308) to 0.828 (genotypes ICCV 10316 to ICCV 92337)

Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS-STING pathway orchestrates an antiviral program that includes type I IFNs and immune-priming of other cell types

A Robust Measure of Tidal Circularization in Coeval Binary Populations: The solar-type spectroscopic Binary Population in The Open Cluster M35

We present a new homogeneous sample of 32 spectroscopic binary orbits in the young (~ 150 Myr) main-sequence open cluster M35. The distribution of orbital eccentricity vs. orbital period (e-log(P)) displays a distinct transition from eccentric to circular orbits at an orbital period of ~ 10 days. The transition is due to tidal circularization of the closest binaries. The population of binary orbits in M35 provide a significantly improved constraint on the rate of tidal circularization at an age of 150 Myr. We propose a new and more robust diagnostic of the degree of tidal circularization in a binary population based on a functional fit to the e-log(P) distribution. We call this new measure the tidal circularization period. The tidal circularization period of a binary population represents the orbital period at which a binary orbit with the most frequent initial orbital eccentricity circularizes (defined as e = 0.01) at the age of the population. We determine the tidal circularizationperiod for M35 as well as for 7 additional binary populations spanning ages from the pre main-sequence (~ 3 Myr) to late main-sequence (~ 10 Gyr), and use Monte Carlo error analysis to determine the uncertainties on the derived circularization periods. We conclude that current theories of tidal circularization cannot account for the distribution of tidal circularization periods with population age.Comment: 37 pages, 9 figures, to be published in The Astrophysical Journal, February 200

Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis

Genetic lesions that activate KRAS account for approximately 30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras-expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles\u27 heel in tumors initiated by oncogenic Kras

Can phylogeny predict chemical diversity and potential medicinal activity of plants? A case study of amaryllidaceae

Background During evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive approach enabling more efficient selection of plants for the development of traditional medicine and lead discovery. However, this relationship has rarely been rigorously tested and the potential predictive power is consequently unknown.Results We produced a phylogenetic hypothesis for the medicinally important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over 100 species. We tested if alkaloid diversity and activity in bioassays related to the central nervous system are significantly correlated with phylogeny and found evidence for a significant phylogenetic signal in these traits, although the effect is not strong.Conclusions Several genera are non-monophyletic emphasizing the importance of using phylogeny for interpretation of character distribution. Alkaloid diversity and in vitro inhibition of acetylcholinesterase (AChE) and binding to the serotonin reuptake transporter (SERT) are significantly correlated with phylogeny. This has implications for the use of phylogenies to interpret chemical evolution and biosynthetic pathways, to select candidate taxa for lead discovery, and to make recommendations for policies regarding traditional use and conservation priorities.<br /

Thermal stress impaired expression of insulin-like growth factor binding proteins in pigs

This study aimed to investigate the correlation of IGFs, IGFBPs, and IGFBPRs of grower pigs with change in temperature humidity index (THI). THI was calculated to know the months of the year when pigs feel discomfort and samples of feed offered were analyzed to know the nutritional availability/deficit. The calculated average THI was above thermal comfort zone for seven months in a year. It was observed that crude protein (CP) and metabolizable energy (ME) availability to pigs were deficient. Gilts of two months age and similar body weight were randomly divided into two groups (n=6); viz. Con-fed animals (feed offered by the farmer) and For-fed animals (formulated feed supplement + Con-fed). The composition of formulated feed supplement was dried leaf of Moringa oleifera, soybean meal, rice mill waste, and mineral mixture. The plasma cortisol level increased in the experimental animals with accelerated THI as evidenced by the strong positive correlation of THI with HSP70 and HSP90. The level of leptin and ghrelin did not have significant relation with the expression level of HSPs in the present study, however, in the control animals, a low level of leptin was observed. The correlation between the growth factors and HSPs was not significant. During the season, where the THI was above the thermal comfort zone, the IGFBPR and IGFBP concentrations were non-significantly increased along with the increased THI