Indiana University-Purdue University Indianapolis (IUPUI) / Literature has demonstrated the ability of human adipose tissue to generate large amounts of lactate. However, it is not understood why adipose tissue produces lactate, how the production of lactate is regulated, and what potential benefit this has to the adipocyte or the organism. We first characterized a human model of adipogenic differentiation with minimal donor to donor variability to assess metabolic changes associated with mature adipocytes compared to their precursors. Indeed, similar to what was observed in human clinical studies, the differentiated adipocytes demonstrated increased lactate production. However, the differentiated adipocytes compared to their precursors (preadipocytes or ASCs) demonstrate an aerobic glycolysis-like (also called Warburg effect-like) increase in glycolysis characterized by a 5.2 fold increase in lactate production in normoxic conditions (atmospheric oxygen tension). Remarkably, this increase in lactate occurred even though the differentiated adipocytes simultaneously demonstrate an increase in oxidative capacity. This low fraction of oxidative capacity coupled with increased lactate production indicated regulation of oxidative rates most likely at the point of pyruvate conversion to either acetyl-CoA (oxidative metabolism) or lactate (glycolytic metabolism). To investigate the potential regulation of this metabolic phenotype, PDK isoform expression was assessed and we found PDK 1 and 4 transcript and protein elevated in the differentiated cells. Non-selective pharmacologic inhibition of the PDKs resulted in decreased lactate production, supporting a regulatory role for PDK in modulation of the observed Warburg effect. PDK inhibition also resulted in increased ROS production in the adipocytes after several hours of treatment and a decrease in cell viability when PDK inhibition was carried out over 36 hours. The resulting loss in viability could be rescued by antioxidant (Tempol) treatment, indicating the decrease in viability was ROS mediated. Similar to what is seen in cancer cells, our data demonstrate that differentiation of human adipocytes is accompanied by a PDK-dependent increase in glycolytic metabolism (Warburg effect) that not only leads to lactate production, but also seems to protect the cells from increased and detrimental generation of ROS.

Knowledge on the precise effects of surplus glucose supply in dairy cows is limited by the lack of information on how intermediary metabolism adapts at different levels of glucose availability. Therefore, a gradual increase of glucose supply via intravenous glucose infusion was used in the present study to test the dose effect of surplus provision of glucose on the metabolic status and milk production of dairy cows. Furthermore, the effects of increasing levels of surplus glucose on mRNA expressions and activities of rate-limiting enzymes involved in hepatic gluconeogenesis were investigated. Based on a previous finding that a positive energy balance may decrease hepatic carnitine palmitoyltransferase (CPT) enzyme activity, it was also of interest whether skeletal muscle CPT activity is downregulated in a similar manner during positive energy balance. Twelve midlactating Holstein-Friesian dairy cows were continuously infused over a 28-d experimental period with either saline (SI group, six cows) or 40% glucose solutions (GI group, six cows). The infusion dose was calculated as a percentage of the daily energy (NEL) requirements by the animal, starting at 0% on d 0 and increasing gradually by 1.25%/d until a maximum dose of 30% was reached by d 24. Dose was then maintained at 30% NEL requirement for 5 d. No infusions were made between d 29-32. Liver and skeletal muscle biopsies were taken on d 0, 8, 16, 24, and 32. Body weight (BW) and back fat thickness (BFT) were recorded on biopsies days. Blood samples were taken every 2 d. In addition, blood samples over 24 h (6-h intervals) were taken the days before each biopsy. Milk and urine samples were taken on biopsies days. BW and BFT increased linearly with increasing glucose dose for GI cows. No differences were observed in the dry matter intake, milk energy output, and energy corrected milk yield between groups. However, milk protein percentage and yield increased linearly in the GI group. Only occasional increases in blood glucose and insulin concentrations were observed in blood samples taken at 1000 h every 2 d. However, during infusion dose of 30% NEL requirements on d 24, GI cows developed postprandial hyperglycemia associated with hyperinsulinemia, coinciding with glucosuria. The revised quantitative insulin sensitivity check index (RQUIKI) indicated linear development of insulin resistance for the GI treatment. GI decreased serum concentrations of beta-hydroxybutyrate (BHBA) and blood urea nitrogen and tended to decrease the serum concentration of non-esterified fatty acids (NEFA). Liver glycogen content increased, while glycogen content in skeletal muscle only tended to increase by GI. No significant changes were observed in the activities and relative mRNA expression levels of hepatic phosphoenolpyruvate carboxykinase and glucose 6-phospatase. The activity of fructose 1,6-bisphosphatase (FBPase) and relative mRNA expression levels of pyruvate carboxylase (PC) were decreased in the GI group but only during the high dose of glucose infusion. Hepatic CPT activity decreased with GI and remained decreased on d 32. The hepatic expression levels of CPT-1A and CPT-2 mRNA were not significantly altered but tended to reflect the changes in enzyme activity. No effect of glucose infusion was observed on skeletal muscle CPT activity. The aforementioned adaptations were reversed four days after the end of glucose infusions except for those of BW, BFT, and lipid metabolism (i.e. serum BHBA and NEFA concentrations, hepatic CPT activity). It is concluded that mid-lactation dairy cows on an energy-balanced diet direct intravenously infused glucose predominantly to body fat reserves but not to increased lactation performance. Cows rapidly adapted to increasing glucose supply but experienced dose-dependent development of insulin resistance corresponding with postprandial hyperglycemia/hyperinsulinemia and glucosuria at dosages equivalent to 30% NEL requirements. The catalytic capacity of key hepatic gluconeogenesis enzymes in mid-lactating dairy cows is not significantly affected by nutritionally relevant increases of glucose supply. Only very high dosages selectively suppress PC transcription and FBPase activity. Finally, it can be concluded that suppression of CPT activity by positive energy balance appears to be specific for the liver in midlactating dairy cows.

I analyzed precision and accuracy of lactation data to reflect actual fawn recruitment for various levels of fecundity, neonatal mortality, harvest intensity, and hunter selectivity. I evaluated and developed a correction equation to adjust for harvest date effects on lactation detectability. I compared metrics of site-specific fawn recruitment (e.g., lactation rates, hunter observation fawn-to-doe ratios, and post-season fawn-to-doe ratios) among themselves, and to site-specific indices of carnivore abundance, for 18 properties across Mississippi and Alabama. Accuracy of lactation rates are compromised due to variation at minimal harvest intensity and insensitivity to change in fetal rate or neonatal mortality. Lactation data can be corrected for harvest date effects on lactation detectability. Hunter observation data are variable and poorly represent fawn recruitment. Lactation data are related to fawn recruitment and can be used to roughly estimate fawn recruitment. Carnivore abundance had neither a significant nor consistent effect on fawn recruitment.

A methodology for ageing foetal and neonatal cattle is developed, involving radiographic examination of infant mandibles for early developmental stages in molariform teeth; tooth-wear methodologies are imprecise at this stage before wear commences. Known-age modern bovine foetal and neonate material are collected as a control assemblage for method development (n=73); six Neolithic to Norse era assemblages from Orkney are examined using the modified technique together with standard tooth-wear analysis and other methodologies. Foetal and died-at-birth material is diagnosed at most sites using the new technique, together with a range of other peri-natal age-groups. Ageing at this early stage is highly relevant in the diagnosis of milking as a palaeoeconomy: the accepted view is that unwanted (male) calves were slaughtered to maximise milk for human consumption, hence a surfeit of neonate calf remains, as at the study sites. The diagnosis of foetal and died-at-birth material challenges this view, suggesting that attritional causes may have contributed to deaths at this stage. Although milking was probably carried out at most of the study sites, this may have been combined with slaughter of cattle for meat in a pragmatic exploitation strategy. Literary research shows possible attritional causes of abortion and early death in calves, in particular dietary insufficiency in pregnant cows, microbial infections, and also inadequate colostrum uptake. Additionally, research is used to consider the challenges to health that early milking might have posed, to the calf as mentioned, but also to the cow, where three main health issues are highlighted: infertility, mastitis and lameness. / The attached files include the Landscape pages and appendices V and VI. Not included are the jpeg Mandible files. A cover sheet was not available.

No description available.

Deer (<i> Odocoileus </i> spp.) are an important cultural and economic resource. They are the most popular game species in the United States and the number one driver of conservation funding. On the other hand, they also cause damage to resources including to the agricultural industry, private property and to humans via deer vehicle collisions. Many areas in eastern North America have experienced a decline in white-tailed deer (<i> Odocoileus virginianus </i>) populations over the past twenty years concurrent with changes in landscape, deer harvest strategies, and increasing and expanding black bear (<i> Ursus americanus </i>) and coyote (<i> Canis latrans </i>) populations. Most studies have addressed this problem at small spatial and temporal scales and in areas where predation was assumed to be limiting population growth. We evaluated white-tailed deer fawn recruitment both directly and indirectly at relatively broader spatial and temporal scales. We studied fawn survival on Marine Corps Base Quantico in Virginia, USA from 2008–2019. We used the Kaplan-Meier estimator, and Cox-proportional hazards models to assess annual survival and factors that influence hazard risk such as sex, weather, landscape composition and configuration and food availability. On Marine Corps Base Quantico, we found an increase in red oak mast abundance increases survival and probability of fawn survival was higher during the first interval of the study (2008–2010; 0.71 [0.52–0.96]; survival probability [CI95%]) than the last three intervals (2011–2013; 0.46 [0.30–0.70]; 2014–2016; 0.48 [0.35–0.66] and 2017–2019; 0.50 [0.39–0.63]). We also found that predation was the leading source of mortality. We assessed recruitment using lactation status from hunter harvest data collected by the Virginia Department of Game and Inland Fisheries during a 22-year period in 30 counties in the Appalachian Mountains of western Virginia. We predicted lactation status as a function of landscape composition and configuration, oak mast abundance, weather, age, and predator detection rates using generalized linear mixed models. We found land cover diversity index positively and black bear detection rate negatively influenced recruitment. Age also predicted lactation status with middle-aged females (3.5–4.5 years old) having a higher lactation probability than mature (≥5.5 years old) age and young (2.5 years old) age class deer. Based on these findings, recruitment is likely to be greater in areas that are heterogeneous. Therefore, if an increase in recruitment is desired silvicultural practices such as fire and timber harvest could be used to permanently change land cover types. These silvicultural practices could also be used to increase the number of oaks on the landscape, and augment production of mature oaks as red oak mast abundance influenced fawn survival. Also reducing predation by manipulating predator densities could improve recruitment. Another potential option which needs further research, would be to reduce predator efficiency by increasing hiding cover for fawns. / Master of Science / Deer (<i> Odocoileus </i> spp.) are an important cultural and economic resource. They are the most popular game species in the United States and the number one driver of conservation funding. Conversely, they also cause damage to resources including to the agricultural industry, private property and to humans via deer vehicle collisions. Some areas in eastern North America have experienced a decline in white-tailed deer (<i> Odocoileus virginianus </i>) populations over the past twenty years concurrent with the colonization of coyotes (<i> Canis latrans </i>) as well as changes in habitat. Therefore, we aimed to determine white-tailed deer fawn survival rates and factors affecting recruitment across a large spatial and temporal scale. Recruitment is when an individual becomes part of the reproductive population. However, for harvestable populations, recruitment is when individuals can be legally harvested for the first time. On Marine Corps Base Quantico from 2008–2019, in Virginia, USA we found that probability of fawn survival was higher during the first interval of the study (2008–2010; 0.71 [0.52–0.96]; survival probability [CI95%]) than the last three intervals (2011–2013; 0.46 [0.30–0.70]; 2014–2016; 0.48 [0.35–0.66] and 2017–2019; 0.50 [0.39–0.63]). We also discovered predation was the leading cause of death and probability of survival increased with increasing red oak mast abundance. Over a large spatial (30 counties) and temporal (22 years) scale we examined fawn recruitment by predicting lactation status of female harvested white-tailed deer in the Appalachians Mountains of western Virginia. We found land cover diversity index positively and black bear (<i> Ursus americanus </i>) detection rate negatively influenced recruitment. Age also predicted lactation status with middle-aged females (3.5–4.5 years old) having a higher lactation probability than mature (≥5.5 years old) age and young (2.5 years old) age class deer. Based on these findings, recruitment is likely to be greater in areas that have a mixture of land cover types. Therefore, if an increase in recruitment is desired silvicultural practices such as fire and timber harvest could be used to permanently change land cover types. These silvicultural practices could also be used to increase the number of oaks on the landscape, and augment production of mature oaks as red oak mast abundance influenced fawn survival. Also reducing predation by manipulating predator densities could improve recruitment. Overall, we found diversity of land cover types, food availability, predators, and age influences population dynamics of white-tailed deer.

<p dir="ltr">Organizational newcomers strive to adjust when they start new jobs, yet little is known about how remote and hybrid work structures influence this process. Previous research has adopted variable-centered approaches to explore the frequency with which newcomers engage in dozens of proactive behaviors in traditional, face-to-face work environments. The current study builds upon this work to capture the socialization process in modern work environments. Adopting a person-centered approach, this study 1.) identifies profiles of newcomers’ perceptions of their work environments, 2.) identifies profiles of newcomer proactive behaviors, 3.) examines the effect of virtuality on these two sets of profiles, and 4.) explores which behavior profiles are associated with the most favorable changes in adjustment.</p>

Des truies ont été assignées à un de trois traitements : 1) témoin (n=22); 2) 30 g j-1 de NuPro® (n=22) et; 3) 60 g j-1 de NuPro® (n=21). Elles recevaient le NuPro® dans 500 g de moulée cubée moulue servie sur la ration, et ce pendant une lactation de 21 jours. Le gras dorsal, le poids, la prise alimentaire, les concentrations sanguines d'IGF-1, d'urée et des acides gras libres, ainsi que la composition du lait (matière sèche, gras, protéine, lactose, nucleotides incluant AMP, CMP, GMP, IMP et UMP) des truies n'ont pas été affectés par les traitements (P> 0,1). Le poids des porcelets en pré- et post-sevrage ainsi que leur prise alimentaire en pouponnière étaient similaires pour tous les groupes (P>0,1). Donner du NuPro® aux truies en lactation ne semble pas avoir d'effets sur les performances zootechniques des truies ou de leurs porcelets.

Le temps passé couché est un aspect important du bien-être des vaches en lactation. Pendant leur cycle de production, celles-ci sont confrontées à plusieurs facteurs de stress pouvant l'entraver. Notamment, la chaleur est reconnue pour diminuer le temps passé couché quotidien de 2 à 4 h/jr chez les vaches en lactation. Plusieurs stratégies peuvent être utilisées afin d'atténuer les réponses physiologiques au stress de chaleur, dont l'inflammation, mais on retrouve peu d'informations sur les changements comportementaux qui y sont associés. Le projet présenté dans ce mémoire avait comme objectifs de déterminer les impacts du stress de chaleur sur le temps passé couché quotidien ainsi que sur le rythme circadien chez des vaches en lactation logées en stabulation entravée et d'évaluer si l'atténuation de l'inflammation par une infusion abomasale d'Oméga-3 peut moduler ces impacts. Nos résultats indiquent une association modérée entre le temps passé couché et les réponses physiologiques au stress de chaleur. Le temps passé couché quotidien (min/jr) des vaches exposées au stress de chaleur était réduit de 2 h/jr comparativement aux vaches gardées en conditions de thermoneutralité. Pour sa part, le temps passé couché quotidien des vaches exposées au stress de chaleur et recevant l'infusion abomasale était plus élevé (+ 1 h/jr) que celui des vaches exposées au stress de chaleur. Une interaction significative entre le traitement et le temps a été mesurée alors que le temps passé couché était réduit pour les deux traitements de stress de chaleur le matin (0000 - 0600 h) et en soirée (1800 - 2400 h) comparativement au traitement de thermoneutralité. Un rythme circadien a été décelé chez tous les traitements. Les vaches gardées en conditions de thermoneutralité avaient la moyenne de temps passé couché par heure, la fluctuation (31,9 min/h) et l'amplitude (11,5 min/h) les plus élevées. Le pic de temps passé couché se produisait chez tous les traitements après minuit, mais plus tôt chez les vaches gardées en thermoneutralité. Ces résultats indiquent que les vaches subissant un stress de chaleur adaptent leur comportement de repos afin de dissiper plus de chaleur et que la réduction de l'inflammation permet de moduler ces adaptations. / Lying time is paramount to dairy cows' welfare. During their production cycle, they are faced with several stress factors that can hinder their resting behavior. Heat is known to reduce daily lying time by 2 to 4 h/d. Several strategies can be used to attenuate physiological responses to heat stress, including inflammation, but there is little information on the behavioral changes associated with it. The project presented in this dissertation had the objectives of determining the impacts of heat stress on the daily lying time as well as on its circadian rhythm in lactating cows housed in tie-stalls and to evaluate whether the attenuation of inflammation by an abomasal infusion of Omega-3 can modulate these impacts. Our results indicate a moderate association between time spent lying down and physiological responses to heat stress. The daily lying time of cows exposed to heat stress was reduced by 2 h/d compared to cows kept in thermoneutrality conditions. For its part, the daily lying time of cows exposed to heat stress and receiving the abomasal infusion was higher (+ 1 h/d) than that of cows exposed to heat stress. A significant interaction between treatment and time was measured as the time spent lying down was reduced for both heat stress treatments in the morning (0000 - 0600 h) and evening (1800 - 2400 h) compared to the thermoneutrality treatment. A circadian rhythm was detected in all treatments. Cows kept in thermoneutrality conditions had the highest average time spent lying down per hour, fluctuation (31.9 min/h) and amplitude (11.5 min/h). The peak time spent lying down occurred in all treatments after midnight, but earlier in cows kept in thermoneutrality relative to other treatments. These results indicate that cows experiencing heat stress adapt their resting behavior to dissipate more heat and that reducing inflammation helps modulate these adaptations.

Ce travail de thèse avait pour but de mieux comprendre, chez les vaches en lactation, le degré de plasticité et d’adaptation des métabolismes énergétique et protéique dans les tissus de l’aire splanchnique et mammaire vis-à-vis une augmentation de l’approvisionnement en acides aminés (AA) en début de lactation ou de l’équilibre des rations avec du tourteau de soya (TS) comparé avec du tourteau de canola (TC), ou ensilage de maïs comparé avec ensilage d’herbe. Dans la première expérience, nous avons déterminé comment un apport accru en AA affectait les performances zootechniques ainsi que les flux nets de lactate, glycérol et β-OH-butyrate, le flux corporel de glucose (FCG) et les flux totaux et nets du glucose dans les tissus drainés par la veine porte (TDVP), le foie et la glande mammaire chez des vaches en début de lactation. Tout d’abord, la perfusion d’AA a augmenté de façon marquée la production de lait et de lactose. Cette expérience a permis de suggérer que les vaches ont des priorités métaboliques pour les AA autres que la néoglucogenèse. Par conséquent, d'autres substrats glucogéniques tels que le lactate et la mobilisation de réserves corporelles jouent un rôle important dans cet intervalle de la transition pour soutenir la demande d’énergie. Dans la deuxième expérience, nous avons comparé les effets d’une source protéique avec un régime à base d'ensilage de maïs, en comparant le TS avec le TC, et de la source de fourrage avec un régime alimentaire à base de TC, comparant l’ensilage de maïs avec l'ensilage d'herbe, en mesurant la production de lait, les paramètres ruminaux, la digestibilité de l’azote ainsi que le métabolisme splanchnique et mammaire des composants énergétiques et protéiques chez des vaches en lactation établie. La substitution de TS par TC répond efficacement aux besoins énergétiques et protéiques au niveau splanchnique et mammaire chez les vaches laitières en lactation. Nos résultats suggèrent qu’une augmentation post-hépatique de l'offre d’AA limitatifs et l'amélioration des interactions énergétiques et protéiques dans l’ensemble splanchnique et mammaire entraînent les augmentations de performances observées avec les rations contenant du TC. / The aim of this study was to better understand, in lactating dairy cows, the degree of plasticity and adaptation of energy and protein metabolism in splanchnic and mammary tissues with an increased amino acid (AA) supply in early lactation or, later in lactation, when rations are balanced with soybean meal (SBM) compared with canola meal (CM), or corn silage compared with grass silage. In the first study, experimental procedures were performed to determine how an increased AA supply affected zootechnical performances together with net flux of lactate, glycerol and β-OH-butyrate, whole body rate of appearance (WB-Ra) of glucose, and total and net fluxes of glucose in portal-drained viscera, liver and mammary gland in cows in established lactation. First, the AA abomasal infusion significantly increased milk and lactose yields. This experience suggests that cows have metabolic priorities for AA other than gluconeogenesis. Therefore, other glucogenic substrates such as lactate and the mobilization of body fat could play an important role in this interval transition to support energy demand. In the second experiment, we have compared the effects of protein source in a corn silage-based diet, comparing soybean meal (SBM) vs. canola meal (CM), and of forage source with CM-based diet, comparing corn vs. grass silage, measuring milk production, ruminal parameters, digestibility of nitrogen and splanchnic and mammary metabolism of energy and nitrogen metabolites in lactating cows in established lactation. In this work, we found that the substitution of SBM by CM responds with efficiency to the splanchnic and mammary needs of energy and protein in lactating dairy cows. With an increased net portal absorption of methionine with CM, observations in this second experiment suggest that a post-liver increased supply of limitative AA and a potential improvement of the energy and protein interaction across the splanchnic and mammary tissues drive the better performances observed in cows fed the CM-based diets.