Effects of negative energy balance on liver gene and protein expression during the early postpartum period and its impacts on dairy cow fertility

End of project reportNegative energy balance (NEB) is a severe metabolic affecting high yielding dairy cows early post partum with both concurrent and latent negative effects on cow fertility as well as on milk production and cow health. The seasonal nature of Irish dairy production necessitates high cow fertility and a compact spring calving pattern in order to maximise grass utilisation. Poor dairy cow reproductive performance currently costs the Irish cattle industry in excess of €400 million annually. High milk yields have been associated with lower reproductive efficiency, and it has been suggested that this effect is probably mediated through its effects on the energy balance of the cow during lactation. The modern high genetic merit dairy cow prioritises nutrient supply towards milk production in early lactation and this demand takes precedence over the provision of optimal conditions for reproduction. In this study we used the bovine Affymetrix 23,000 gene microarray, which contains the most comprehensive set of bovine genes to be assembled and provides a means of investigating the modifying influences of energy balance on liver gene expression. Cows in severe negative energy balance (SNEB) in early lactation showed altered hepatic gene expression in metabolic processes as well as a down regulation of the insulin-like growth factor (IGF) system, where insulin like growth factor-1 (IGF-1), growth hormone receptor variant 1A (GHR1A) and insulin-like growth factor binding protein-acid labile subunit (IGFBP-ALS) were down regulated compared to the cows in the moderate negative energy balance MNEB group, consistent with a five-fold reduction in systemic concentrations of IGF1 in the SNEB group.Cows in SNEB showed elevated expression of key genes involved in the inflammatory response such as interleukin-8 (IL-8). There was a down regulation of genes involved in cellular growth in SNEB cows and moreover a negative regulator of cellular proliferation (HGFIN) was up regulated in SNEB cows, which is likely to compromise adaptation and recovery from NEB. The puma method of analysis revealed that 417 genes were differentially regulated by EB (P<0.05), of these genes 190 were up-regulated while 227 were down-regulated, with 405 genes having known biological functions. From Ingenuity Pathway Analysis (IPA), lipid catabolism was found to be the process most affected by differences in EB status

Events, processes, and the time of a killing

The paper proposes a novel solution to the problem of the time of a killing (ToK), which persistently besets theories of act-individuation. The solution proposed claims to expose a crucial wrong-headed assumption in the debate, according to which ToK is essentially a problem of locating some event that corresponds to the killing. The alternative proposal put forward here turns on recognizing a separate category of dynamic occurents, viz. processes. The paper does not aim to mount a comprehensive defense of process ontology, relying instead on extant defenses. The primary aim is rather to put process ontology to work in diagnosing the current state of play over ToK, and indeed in solving it

Galactic Center Radio Constraints on Gamma-Ray Lines from Dark Matter Annihilation

Recent evidence for one or more gamma-ray lines at ~ 130 GeV in the Fermi-LAT data from the Galactic Center has been interpreted as a hint for dark matter annihilation to Z{\gamma} or H{\gamma} with an annihilation cross section, ~ 10^{-27} cm^3 s^{-1} . We test this hypothesis by comparing synchrotron fluxes due to the electrons and positrons from the decay of the Z or the H boson only in the Galactic Center against radio data from the same region in the Galactic Center. We find that the radio data from single dish telescopes marginally constrain this interpretation of the claimed gamma lines for a contracted NFW profile. Already-operational radio telescopes such as LWA, VLA-Low and LOFAR, and future radio telescopes like SKA, which are sensitive to annihilation cross sections as small as 10^{-28} cm^3 s^{-1}, can confirm or rule out this scenario very soon. We discuss the assumptions on the dark matter profile, magnetic fields, and background radiation density profiles, and show that the constraints are relatively robust for any reasonable assumptions. Independent of the above said recent developments, we emphasize that our radio constraints apply to all models where dark matter annihilates to Z{\gamma} or H{\gamma}.Comment: v3: 18 pages, 7 figures. Minor changes. Published in Phys. Rev.

Is attending a mental process?

The nature of attention has been the topic of a lively research programme in psychology for over a century. But there is widespread agreement that none of the theories on offer manage to fully capture the nature of attention. Recently, philosophers have become interested in the debate again after a prolonged period of neglect. This paper contributes to the project of explaining the nature of attention. It starts off by critically examining Christopher Mole’s prominent “adverbial” account of attention, which traces the failure of extant psychological theories to their assumption that attending is a kind of process. It then defends an alternative, process-based view of the metaphysics of attention, on which attention is understood as an activity and not, as psychologists seem to implicitly assume, an accomplishment. The entrenched distinction between accomplishments and activities is shown to shed new light on the metaphysics of attention. It also provides a novel diagnosis of the empirical state of play

Langley's CSI evolutionary model: Phase O

A testbed for the development of Controls Structures Interaction (CSI) technology to improve space science platform pointing is described. The evolutionary nature of the testbed will permit the study of global line-of-sight pointing in phases 0 and 1, whereas, multipayload pointing systems will be studied beginning with phase 2. The design, capabilities, and typical dynamic behavior of the phase 0 version of the CSI evolutionary model (CEM) is documented for investigator both internal and external to NASA. The model description includes line-of-sight pointing measurement, testbed structure, actuators, sensors, and real time computers, as well as finite element and state space models of major components

A higher degree of resilience: Using psychometric testing to reveal the benefits of university internship placements

Resilience is a multi-faceted concept but, in the context of learning, it can best be thought of as an individual’s capacity to create and maximise opportunities as well as responding positively to setbacks and challenges. Developing students’ resilience is becoming increasingly important. Research has shown resilience links to attainment, retention, engagement and employability. However, very little work has examined what aspects of curricula enhance resilience and the particular role of active learning frameworks in achieving this. Here, we analyse the effects of optional real-world internship placements on eight measures of resilience. Psychometric testing was conducted twice per student – at the start of their second academic year and again at the end. Students choosing an internship had significantly higher challenge orientation and adaptability scores than other students in the same cohort. Adaptability of both interns and non-interns improved over the academic year, but improvement was significantly higher for interns. Scores for optimism, purposeful direction, and ingenuity significantly increased between start-of-year and end-of-year tests for interns versus a decline for non-interns. We conclude that facilitating student engagement with real-world issues and challenges through supported internships within an active learning framework is an important mechanism for increasing students’ resilience

A Whole-Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response.

Insulin production by the pancreatic β-cell is required for normal glucose homeostasis. While key transcription factors that bind to the insulin promoter are known, relatively little is known about the upstream regulators of insulin transcription. Using a whole-genome RNA interference screen, we uncovered 26 novel regulators of insulin transcription that regulate diverse processes including oxidative phosphorylation, vesicle traffic, and the unfolded protein response (UPR). We focused on Spry2-a gene implicated in human type 2 diabetes by genome-wide association studies but without a clear connection to glucose homeostasis. We showed that Spry2 is a novel UPR target and its upregulation is dependent on PERK. Knockdown of Spry2 resulted in reduced expression of Serca2, reduced endoplasmic reticulum calcium levels, and induction of the UPR. Spry2 deletion in the adult mouse β-cell caused hyperglycemia and hypoinsulinemia. Our study greatly expands the compendium of insulin promoter regulators and demonstrates a novel β-cell link between Spry2 and human diabetes