Heat stress (HS) jeopardizes human and animal health and reduces animal agriculture productivity; however, its pathophysiology is not well understood. Study objectives were to evaluate the direct effects of HS on carbohydrate and lipid metabolism. Female pigs (57 ± 5 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 20°C) and were ad libitum fed. During period 2, pigs were exposed to: (1) constant HS conditions (32°C) and fed ad libitum (n = 7), or (2) TN conditions and pair-fed (PFTN; n = 10) to minimize the confounding effects of dissimilar feed intake. All pigs received an intravenous glucose tolerance test (GTT) and an epinephrine challenge (EC) in period 1, and during the early and late phases of period 2. After 8 days of environmental exposure, all pigs were killed and tissue samples were collected. Despite a similar reduction in feed intake (39%), HS pigs tended to have decreased circulating nonesterified fatty acids (NEFA; 20%) and a blunted NEFA response (71%) to the EC compared to PFTN pigs. During early exposure, HS increased basal circulating C-peptide (55%) and decreased the insulinogenic index (45%) in response to the GTT. Heat-stressed pigs had a reduced T3 to T4 ratio (56%) and hepatic 5′-deiodinase activity (58%). After 8 days, HS decreased or tended to decrease the expression of genes involved in oxidative phosphorylation in liver and skeletal muscle, and ATGL in adipose tissue. In summary, HS markedly alters both lipid and carbohydrate metabolism independently of nutrient intake.

Isom SC, Stevens JR, Li R, Spollen WG, Cox L, Spate LD, Murphy CN, Prather RS. Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies. Physiol Genomics 45: 577-589, 2013. First published May 21, 2013 doi:10.1152/physiolgenomics.00094.2012.-Substantial mortality of in vitro manipulated porcine embryos is observed during peri-attachment development. Herein we describe our efforts to characterize the transcriptomes of embryonic disc (ED) and trophectoderm (TE) cells from porcine embryos derived from in vivo fertilization, in vitro fertilization (IVF), parthenogenetic oocyte activation (PA), and somatic cell nuclear transfer (SCNT) on days 10, 12, and 14 of gestation. The IVF, PA, and SCNT embryos were generated with in vitro matured oocytes and were cultured overnight in vitro before being transferred to recipient females. Sequencing of cDNA from the resulting embryonic samples was accomplished with the Genome Analyzer IIx platform from Illumina. Reads were aligned to a custom-built swine transcriptome. A generalized linear model was fit for ED and TE samples separately, accounting for embryo type, gestation day, and their interaction. Those genes with significant differences between embryo types were characterized in terms of gene ontologies and KEGG pathways. Transforming growth factor-␤ signaling was downregulated in the EDs of IVF embryos. In TE cells from IVF embryos, ubiquitin-mediated proteolysis and ErbB signaling were aberrantly regulated. Expression of genes involved in chromatin modification, gene silencing by RNA, and apoptosis was significantly disrupted in ED cells from SCNT embryos. In summary, we have used high-throughput sequencing technologies to compare gene expression profiles of various embryo types during peri-attachment development. We expect that these data will provide important insight into the root causes of (and possible opportunities for mitigation of) suboptimal development of embryos derived from assisted reproductive technologies.in vitro fertilization; parthenogenesis; somatic cell nuclear transfer; in vitro embryo production; Illumina; ART IN MOST MAMMALIAN SPECIES studied to date, only 50 -70% of successfully fertilized oocytes will give rise to live, healthy offspring (reviewed in Refs. 20,57,79). Some embryos succumb to the effects of chromosomal abnormalities or faulty uterine environments, for example. But the underlying cause behind most early embryonic mortality is still poorly understood. Such inefficiency is concerning to human fertility clinical practitioners and to animal producers in agricultural settings as well. Embryos produced by assisted reproductive technologies (ART) are generally less fit and more prone to failure than in vivo produced embryos. It has been presupposed that oocyte maturation and embryo culture systems that are inadequate to promote proper development are primarily to blame, yet the precise mechanisms that contribute to deficiencies in developmental potential in in vitr...

There is compelling evidence that oocytes from mares >18 years of age have a high incidence of inherent defects that result in early embryonic loss. In women, an age-related decrease in oocyte quality is associated with an increased incidence of aneuploidy and it has recently been determined that the gene expression profile of human oocytes is altered with advancing age. We hypothesised that similar age-related aberrations in gene expression occur in equine oocytes. Therefore, the aim of the present study was to compare gene expression profiles of individual oocytes and cumulus cells from young and aged mares, specifically evaluating genes that have been identified as being differentially expressed with advancing maternal age and/or aneuploidy in human oocytes. Expression of 48 genes was compared between 14 cumulus-oocyte complexes (COCs) from mares aged 3-12 years and 10 COCs from mares ≥18 years of age. Three genes (mitochondrial translational initiation factor 3 (IF3), heat shock transcription factor 5 (HSF5) and Y box binding protein 2 (YBX2)) were differentially expressed in oocytes, with all being more abundant in oocytes from young mares. Three genes (ADP-ribosylation factor-like 6 interacting protein 6 (ARL6IP6), BCL2-associated X protein (BAX) and hypoxia upregulated 1 (HYOU1)) were differentially expressed in cumulus cells, with all being more abundant in aged mares. The results of the present study confirm there are age-related differences in gene expression in equine COCs, which may be associated with the lower quality and decreased developmental competence of oocytes from aged mares.

Addictive drugs are responsible for mass killing. Neither persons with addiction nor the general populace seem conscious of the malevolence of governments and drug dealers working together. How could this be? What is the place of psychoanalysis in thinking about deaths from addiction and in responding to patients with addiction? To answer these questions, we revise concepts of SEEKING, drive, instinct, pleasure, and unpleasure as separable. We review the neurobiological mechanism of cathexis. We discuss how addictive drugs take over the will by changing the SEEKING system. We review how opioid tone in the central nervous system regulates human relationships and how this endogenous hormonal system is modified by external opioid administration. We differentiate the pleasure of relatedness from the unpleasure of urgent need including the urgent need for drugs. We show how addictive drug-induced changes in the SEEKING system diminish dopaminergic tone, reducing the motivation to engage in the pursuit of food, water, sex, sleep, and relationships in favor of addictive drugs. With this neuropsychoanalytic understanding of how drugs work, we become more confidently conscious of our ability to respond individually and socially.

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