Investigating the interplay of physiological and molecular mechanisms underpinning programmable aspects of heat stress in pigs

Heat stress (HS) undermines production efficiency in all animal agriculture, culminating in major economic losses annually. The effects of HS in pigs is realized through depressed growth, altered body composition, and impaired reproductive performance. Pigs, unlike other mammals, do not possess functional sweat glands, making them rely on other mechanisms to thermoregulate during a heat challenge. Continual investigation of hyperthermia in pigs is crucial for developing new strategies and/or technologies that mitigate the effects of HS imposed on the pork industry. The studies conducted in this dissertation investigate the complex interplay of whole-animal physiology as well as cellular and molecular mechanisms within specific tissues. Identifying pigs demonstrating HS tolerance without compromising productivity would be valuable. Thus, study 1 (chapter 2) was carried out to evaluate the degree to which thermoregulatory responses are associated with production phenotypes during acute HS. Hyperthermic pigs accumulate more adipose tissue than their feed intake predicts, which may be mediated by HS-induced hyperinsulinemia. However, less is known how HS influences fatty acid composition and adipocyte size, both of which are regulated by insulin and can influence carcass fat quality. To better understand the underlying physiology of how HS influences body composition, study 2 (chapter 3) investigated insulin’s potential role in affecting adipose characteristics during HS. A cardinal physiological response to HS is compromised intestinal integrity and concomitant increased gut-derived lipopolysaccharide (LPS) into systemic circulation. While HS causes female infertility, many of the reproductive consequences imposed by the abiotic factor are also recapitulated by direct exposures to LPS independently. Additionally, heat shock proteins are known as molecular stress responders, but their roles during in vivo periods of stress in the ovary are ill-defined. Thus, study 3 (chapter 4) was conducted to evaluate the direct and indirect (i.e., LPS) effects of HS on ovarian heat shock protein machinery. Recent studies also demonstrate that body composition and metabolic responses to HS can also be programmed via gestational HS, directly impacting the progeny’s postnatal development. Developmental programming is mediated through specific epigenetic mechanisms and study 4 (chapter 5) investigated alterations to DNA methylation and protein responses in muscle as a result of intrauterine HS. In conclusion, the cumulative discoveries within this dissertation expands our knowledge regarding the negative consequences of thermal biology in pigs, a pivotal step for mitigating the deleterious effects of environmental HS on animal health and performance

Physiological mechanisms through which heat stress compromises reproduction in pigs

Seasonal variations in environmental temperatures impose added stress on domestic species bred for economically important production traits. These heat‐mediated stressors vary on a seasonal, daily, or spatial scale, and negatively impact behavior and reduce feed intake and growth rate, which inevitably lead to reduced herd productivity. The seasonal infertility observed in domestic swine is primarily characterized by depressed reproductive performance, which manifests as delayed puberty onset, reduced farrowing rates, and extended weaning‐to‐estrus intervals. Understanding the effects of heat stress at the organismal, cellular, and molecular level is a prerequisite to identifying mitigation strategies that should reduce the economic burden of compromised reproduction. In this review, we discuss the effect of heat stress on an animal\u27s ability to maintain homeostasis in multiple systems via several hypothalamic‐pituitary‐end organ axes. Additionally, we discuss our understanding of epigenetic programming and how hyperthermia experienced in utero influences industry‐relevant postnatal phenotypes. Further, we highlight the recent recognized mechanisms by which distant tissues and organs may molecularly communicate via extracellular vesicles, a potentially novel mechanism contributing to the heat‐stress response

Genome-Wide Association Analyses of Biological Responses to Heat Stress in Pigs

With genetic selection for rapid, lean tissue accretion, pigs are becoming increasingly sensitive to heat stress (HS) due to their physiological limitations such as the lack of functional sweat glands to effectively dissipate heat. Increased respiration rate and reduced feed intake are immediate and conserved biological responses to HS in pigs and other livestock species. Genetic differences in how animals respond to high ambient temperatures have been previously reported, but genetic factors contributing to the response variability remain ill-defined. In this study, porcine high density single nucleotide polymorphism (SNP) beadchips were used to genotype 236 female pigs who had been exposed to HS conditions, and analyzed to detect chromosomal regions associated with biological responses measured before and after HS, including rectal temperature, respiration rate, feed intake, and body weight loss. We identified significant gene region associations for rectal temperature on SSC12, respiration rate on SSC14 and SSC16, as well as feed efficiency and weight loss on SSC13. Further analyses of these detected regions will likely reveal potential candidate genes and suggest molecular mechanisms contributing to the variability in the biological response of pigs to environmentally-induced hyperthermia

A mass spectrometry imaging based approach for prognosis prediction in UICC stage I/II colon cancer

Simple Summary Tumor treatment is heavily dictated by the tumor progression status. However, in colon cancer, it is difficult to predict disease progression in the early stages. In this study, we have employed a proteomic analysis using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). MALDI-MSI is a technique that measures the molecular content of (tumor) tissue. We analyzed tumor samples of 276 patients. If the patients developed distant metastasis, they were considered to have a more aggressive tumor type than the patients that did not. In this comparative study, we have developed bioinformatics methods that can predict the tendency of tumor progression and advance a couple of molecules that could be used as prognostic markers of colon cancer. The prediction of tumor progression can help to choose a more adequate treatment for each individual patient. Abstract Currently, pathological evaluation of stage I/II colon cancer, following the Union Internationale Contre Le Cancer (UICC) guidelines, is insufficient to identify patients that would benefit from adjuvant treatment. In our study, we analyzed tissue samples from 276 patients with colon cancer utilizing mass spectrometry imaging. Two distinct approaches are herein presented for data processing and analysis. In one approach, four different machine learning algorithms were applied to predict the tendency to develop metastasis, which yielded accuracies over 90% for three of the models. In the other approach, 1007 m/z features were evaluated with regards to their prognostic capabilities, yielding two m/z features as promising prognostic markers. One feature was identified as a fragment from collagen (collagen 3A1), hinting that a higher collagen content within the tumor is associated with poorer outcomes. Identification of proteins that reflect changes in the tumor and its microenvironment could give a very much-needed prediction of a patient’s prognosis, and subsequently assist in the choice of a more adequate treatment

The effects of inclination on a two stage pulse tube cryocooler for use with a ground based observatory

Abstract Ground-based observatories across a wide range of wavelengths implement cryogenic cooling techniques to increase the sensitivity of instruments and enable low temperature detector technologies. Commercial pulse tube cryocoolers (PTCs) are frequently used to provide 40 K and 4 K stages as thermal shells in scientific instruments. However, PTC operation is dependent on gravity, giving rise to changes in cooling capacity over the operational tilt range of pointed telescopes. We present a study of the performance of a two stage PTC with a cooling capacity of 1.8 W at 4.2 K and 50 W at 45 K (Cryomech PT420-RM) from 0 - 55 ° away from vertical to probe capacity as a function of angle over a set of realistic thermal loading conditions. Our study provides a method to extract temperature estimates given predicted thermal loading conditions across the angular range sampled. We then discuss the design implications for current and future tilted cryogenic systems

Gestational Heat Stress Alters Postnatal Offspring Body Composition Indices and Metabolic Parameters in Pigs

The study objectives were to test the hypothesis that heat stress (HS) during gestational development alters postnatal growth, body composition, and biological response to HS conditions in pigs. To investigate this, 14 first parity crossbred gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or HSHS) during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN, cyclical 18–22°C) or HS conditions (cyclical 28–34°C) during the entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were heat-stressed for the first or second half of gestation, respectively. Postnatal offspring were exposed to one of two thermal environments for an acute (24 h) or chronic (five weeks) duration in either constant TN (21°C) or HS (35°C) environment. Exposure to chronic HS during their growth phase resulted in decreased longissimus dorsi cross-sectional area (LDA) in offspring from HSHS and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs from dams that experienced HS during the first half of gestation (HSHS and HSTN) had increased (13.9%) subcutaneous fat thickness compared to pigs from dams exposed to TN conditions during the first half of gestation. This metabolic repartitioning towards increased fat deposition in pigs from dams heat-stressed during the first half of gestation was accompanied by elevated blood insulin concentrations (33%; P = 0.01). Together, these results demonstrate HS during the first half of gestation altered metabolic and body composition parameters during future development and in biological responses to a subsequent HS challenge