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

LOW ENERGY SUPERSYMMETRY PHENOMENOLOGY

We summarize the current status and future prospects for low energy (weak scale) supersymmetry. In particular, we evaluate the capabilities of various $e^+e^-$, $p\bar p$ and $pp$ colliders to discover evidence for supersymmetric particles. Furthermore, assuming supersymmetry is discovered, we discuss capabilities of future facilities to dis-entangle the anticipated spectrum of super-particles, and, via precision measurements, to test mass and coupling parameters for comparison with various theoretical expectations. We comment upon the complementarity of proposed hadron and $e^+e^-$ machines for a comprehensive study of low energy supersymmetry.Comment: 74 page (Latex) file; a PS or uuencoded manuscript with embedded figures is available via anonymous ftp at ftp://hep.fsu.edu/preprints/baer/FSUHEP950401.ps or .uu . Contributed chapter to DPF study group on Electroweak Symmetry Breaking and Beyond the Standard Model

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

Surgery Versus Radiotherapy for Clinically-localized Prostate Cancer: A Systematic Review and Meta-analysis

AbstractContextTo date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.ObjectiveTo conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.Evidence acquisitionWe searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.Evidence synthesisNineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54–1.73, p<0.00001; I2=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76–2.47, p < 0.00001; I2=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.ConclusionsRadiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.Patient summaryWe reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery

Do About Half the Top Quarks at FNAL Come From Gluino Decays?

We argue that it is possible to make a consistent picture of FNAL data including the production and decay of gluinos and squarks. The additional cross section is several pb, about the size of that for Standard Model (SM) top quark pair production. If the stop squark mass is small enough, about half of the top quarks decay to stop squarks, and the loss of SM top quark pair production rate is compensated by the supersymmetric processes. This behavior is consistent with the reported top quark decay rates in various modes and other aspects of the data, and suggests several other possible decay signatures. This picture can be tested easily with more data, perhaps even with the data in hand, and demonstrates the potential power of a hadron collider to determine supersymmetric parameters. It also has implications for the top mass measurement and the interpretation of the LEP $R_b$ excess.Comment: 18 pages, including 4 Postscript figures, uses epsf.tex, also available at http://www.hep.anl.gov/theory/mrenna

‘Is every YouTuber going to make a coming out video eventually?’: YouTube celebrity video bloggers and lesbian and gay identity

A significant number of YouTube celebrity video bloggers (vloggers) have used the platform to come out publicly as lesbian or gay. This article interrogates the cultural work of YouTube celebrity coming outs, through the case studies of two of the most prominent gay vloggers: Ingrid Nilsen and Connor Franta. This article explores how the coming out moments of these vloggers, as articulated in their coming out vlogs and the wider media discourses surrounding these, make legible a normative gay youth subject position which is shaped by the specific tropes, conventions and commercial rationale of YouTube fame itself. I define this subject position as 'proto-homonormative.' It positions a "successful" gay adulthood, defined through the neoliberal ideals of authenticity, self-branding and individual enterprise bound to the phenomenon of YouTube celebrity, as contingent upon a particular personal relationship with one's non-normative sexuality. I interrogate how the emotional contours of Nilsen and Franta’s coming out narratives, their represented abilities to channel their non-normative sexualities into lucrative celebrity brands, and their construction as gay and lesbian ‘role models’ by the mainstream media, delineates a journey into "acceptance" and "pride" in one's gay sexuality as the expected narrative of contemporary gay life. This narrative, I argue, cements the default normativity of heterosexuality in mainstream culture, and produces a narrow framework of “acceptable” gay youth subjectivity which is aligned with the ideals of neoliberalism embodied in the figure of the YouTube celebrity vlogger

Gene expression in hypothalamus, liver, and adipose tissues and food intake response to melanocortin-4 receptor agonist in pigs expressing melanocortin-4 receptor mutations

Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular injection of melanocortin-4 receptor (MC4R) agonist [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH) in pigs homozygous for the missense mutation in the MC4R, D298 allele (n = 12), N298 allele (n = 12), or heterozygous (n = 12). Food intake (FI) was measured at 12 and 24 h after treatment. All pigs were killed at 24 h after treatment, and hypothalamus, liver, and back-fat tissue was collected. NDP-MSH suppressed (P \u3c 0.004) FI at 12 and 24 h in all animals after treatment. In response to NDP-MSH, 278 genes in hypothalamus (q ≤ 0.07, P ≤ 0.001), 249 genes in liver (q ≤ 0.07, P ≤ 0.001), and 5,066 genes in fat (q ≤ 0.07, P ≤ 0.015) were differentially expressed. Pathway analysis of NDP-MSH-induced differentially expressed genes indicated that genes involved in cell communication, nucleotide metabolism, and signal transduction were prominently downregulated in the hypothalamus. In both liver and adipose tissue, energy-intensive biosynthetic and catabolic processes were downregulated in response to NDP-MSH. This included genes encoding for biosynthetic pathways such as steroid and lipid biosynthesis, fatty acid synthesis, and amino acid synthesis. Genes involved in direct energy-generating processes, such as oxidative phosphorylation, electron transport, and ATP synthesis, were upregulated, whereas TCA-associated genes were prominently downregulated in NDP-MSH-treated pigs. Our data also indicate a metabolic switch toward energy conservation since genes involved in energy-intensive biosynthetic and catabolic processes were downregulated in NDP-MSH-treated pigs

Feeding the Worlth Healthily: the Challenge of Measuring the effects of Agriculture on Health

Agricultural production, food systems and population health are intimately linked. While there is a strong evidence base to inform our knowledge of what constitutes a healthy human diet, we know little about actual food production or consumption in many populations and how developments in the food and agricultural system will affect dietary intake patterns and health. The paucity of information on food production and consumption is arguably most acute in low- and middle-income countries, where it is most urgently needed to monitor levels of under-nutrition, the health impacts of rapid dietary transition and the increasing ‘double burden’ of nutrition-related disease. Food availability statistics based on food commodity production data are currently widely used as a proxy measure of national-level food consumption, but using data from the UK and Mexico we highlight the potential pitfalls of this approach. Despite limited resources for data collection, better systems of measurement are possible. Important drivers to improve collection systems may include efforts to meet international development goals and partnership with the private sector. A clearer understanding of the links between the agriculture and food system and population health will ensure that health becomes a critical driver of agricultural change