Transcriptional Profiling of the Caloric Restriction in Key Metabolic Tissues of Pigs Differing in Feed Efficiency

Residual feed intake is a measure of feed efficiency, where low RFI denotes high feed efficiency. Caloric restriction (CR) is associated with feed efficiency in livestock species and to human health benefits such as longevity and cancer prevention. We have developed pig lines that differ in RFI and we are interested in identifying the genes and pathways that underlie feed efficiency. Prepubertal Yorkshire gilts with low RFI (n=10) or high RFI (n=10) were fed ad libitum or at 80% of maintenance for 8 days. We measured serum metabolites and generated transcriptional profiles of liver and subcutaneous adipose tissue on these animals. Overall, 6,114 genes in fat and 305 genes in liver were differentially expressed (DE) in response to CR, and 311 genes in fat and 147 genes in liver were DE due to RFI differences. Pathway analyses of CR-induced DE genes indicated a dramatic switch to a conservation mode of energy usage by down-regulating lipogenesis and steroidogenesis in both liver and fat. Interestingly, CR altered expression of genes in immune and cell cycle/apoptotic pathways in fat, which may explain part of the CR-driven lifespan enhancement. In-silico analysis of transcription factors revealed ESR1 as a putative regulator of the adaptive response to CR, as several targets of ESR1 in our DE fat genes were annotated as cell cycle/apoptosis genes. The lipid metabolic pathway was overrepresented by down-regulated genes due to both CR and low RFI. We propose a common energy conservation mechanism, which may be controlled by PPARA, PPARG, and/or CREB in both CR and feed efficient pigs

Use of Transcriptional Profiling and Assessment of Blood Parameters to Understand Biological Mechanisms Controlling Feed Intake and Efficiency in Pigs

In this study, using transcriptional profiling of key tissues, we aimed to identify genetic mechanisms differing between control pigs and pigs that have been under selection for low residual feed intake (RFI) for three generations. A further aim was to determine the pathways responding to feed restriction within these lines and any line x treatment interactions resulting in gene expression differences. Preliminary results indicate that 2,809 genes in fat (p\u3c0.04, q\u3c0.2) and 61 genes in liver (p\u3c0.001, q\u3c0.2) showed differential expression in response to feed restriction. Also, 1,247 genes (p\u3c0.02, q\u3c0.2) showed differential expression between low RFI and control pigs and 38 genes (p\u3c0.001, q\u3c0.2) showed a line x feed interaction in liver. In addition, we measured the concentration of some of the important feed intake regulators in the blood such as leptin, triglyceride, and glucose. We found that the average blood leptin level to be significantly higher in the control ad libitum (CA) pigs than the control restricted (CR) group. Interestingly, the selected line of pigs on both restricted (SR) and ad libitum (SA) feed had similar blood leptin levels as found in the CR group pigs. Serum glucose levels were higher in CR than CA, however, we observed an opposite trend in the selected group. Combined with the transcriptional profiling results, blood hormone parameters may help us understand potential pathways that control FI and FE in pigs

Morphological analysis on the coherence of kHz QPOs

We take the recently published data of twin kHz quasi-period oscillations (QPOs) in neutron star (NS) lowmass X-ray binaries (LMXBs) as the samples, and investigate the morphology of the samples, which focuses on the quality factor, peak frequency of kHz QPOs, and try to infer their physical mechanism. We notice that: (1) The quality factors of upper kHz QPOs are low (2 ~ 20 in general) and increase with the kHz QPO peak frequencies for both Z and Atoll sources. (2) The distribution of quality factor versus frequency for the lower kHz QPOs are quite different between Z and Atoll sources. For most Z source samples, the quality factors of lower kHz QPOs are low (usually lower than 15) and rise steadily with the peak frequencies except for Sco X-1, which drop abruptly at the frequency of about 750 Hz. While for most Atoll sources, the quality factors of lower kHz QPOs are very high (from 2 to 200) and usually have a rising part, a maximum and an abrupt drop. (3) There are three Atoll sources (4U 1728-34, 4U 1636-53 and 4U 1608-52) of displaying very high quality factors for lower kHz QPOs. These three sources have been detected with the spin frequencies and sidebands, in which the source with higher spin frequency presents higher quality factor of lower kHz QPOs and lower difference between sideband frequency and lower kHz QPO frequency.Comment: 8 pages, 8 figures, publishe

Complex patterns of spontaneous initiations and terminations of reentrant circulation in a loop of cardiac tissue

A two-component model is developed that consists of a discrete loop of cardiac cells that circulates action potentials together with a cardiac pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and their interactions with the pacer are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability of reentrant circulation (T-bistability) and in some cases, also phase-resetting interactions with the pacer.Comment: 27 pages, 10 figures, 61 references; A version of this paper (same results) is to appear in the Journal of Theoretical Biology; arXiv V2 adds helpful commments to facilitate reading and corrects minor errors in presentatio

Partial Wave Analysis of J/ψ→γ(K+K−π+π−)J/\psi \to \gamma (K^+K^-\pi^+\pi^-)

BES data on $J/\psi \to \gamma (K^+K^-\pi^+\pi^-)$ are presented. The $K^*\bar K^*$ contribution peaks strongly near threshold. It is fitted with a broad $0^{-+}$ resonance with mass $M = 1800 \pm 100$ MeV, width $\Gamma = 500 \pm 200$ MeV. A broad $2^{++}$ resonance peaking at 2020 MeV is also required with width $\sim 500$ MeV. There is further evidence for a $2^{-+}$ component peaking at 2.55 GeV. The non-$K^*\bar K^*$ contribution is close to phase space; it peaks at 2.6 GeV and is very different from $K^{*}\bar{K^{*}}$.Comment: 15 pages, 6 figures, 1 table, Submitted to PL

Mixture of latent trait analyzers for model-based clustering of categorical data

Model-based clustering methods for continuous data are well established and commonly used in a wide range of applications. However, model-based clustering methods for categorical data are less standard. Latent class analysis is a commonly used method for model-based clustering of binary data and/or categorical data, but due to an assumed local independence structure there may not be a correspondence between the estimated latent classes and groups in the population of interest. The mixture of latent trait analyzers model extends latent class analysis by assuming a model for the categorical response variables that depends on both a categorical latent class and a continuous latent trait variable; the discrete latent class accommodates group structure and the continuous latent trait accommodates dependence within these groups. Fitting the mixture of latent trait analyzers model is potentially difficult because the likelihood function involves an integral that cannot be evaluated analytically. We develop a variational approach for fitting the mixture of latent trait models and this provides an efficient model fitting strategy. The mixture of latent trait analyzers model is demonstrated on the analysis of data from the National Long Term Care Survey (NLTCS) and voting in the U.S. Congress. The model is shown to yield intuitive clustering results and it gives a much better fit than either latent class analysis or latent trait analysis alone

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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