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Although the actions of dopamine throughout the brain are clearly linked to motivation and cognition, the specific role(s) of dopamine in the CA1 subfield of the ventral hippocampus (vH) is unresolved. Prior preclinical studies suggest that dopamine D 3 receptors (D 3 R) expressed on CA1 pyramidal cells exhibit a unique capacity to modulate mechanisms of long-term synaptic plasticity, but less is known about how interneurononal inputs modulate these cells. We hypothesized that inputs from μ opioid receptor (MOR)-expressing inhibitory interneurons selectively modulate the activity of postsynaptic D 3 Rs expressed on CA1 principal cells to shape neurotransmission in the rat vH. We used the whole-cell voltage clamp technique to test this hypothesis by measuring evoked inhibitory postsynaptic currents (eIPSCs) from CA1 principal cells in vH slices or GABA A currents from acutely dissociated vH neurons. The eIPSC response recorded from CA1 neurons in vH slices was inhibited by either the MOR agonist DAMGO or the D 3 R agonist PD128907, but pretreatment with DAMGO occluded any further inhibition by PD128907. GABAA currents measured in acutely dissociated vH CA1 neurons were inhibited by D 3 R activation via PD128907, consistent with postsynaptic localization of D 3 receptors. Kinetic alterations induced by the neuromodulatory agonists are consistent with selective targeting of postsynaptic D 3 Rs expressed on CA1 principal cells by MOR-expressing GABAergic inputs. Our findings suggest postsynaptic D 3 R-mediated modulation of MOR-expressing GABAergic inputs is a site at which dopaminergic and opioidergic activity may contribute to disinhibition of vH excitatory neurotransmission, and, thus, influence critical physiological processes such as synaptic plasticity and network oscillations.

Brominated flame retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of hexabromocyclododecane (HBCD) exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus-derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (current use), HBCD (phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All 3 BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 μM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed that BFR exposure increased LC3-II conversion and autophagosome/autolysosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared with the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex protein SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of changes in vesicular trafficking., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Brominated flame retardants are used in many household products to reduce flammability, but often leach into the surrounding environment over time. Hexabromocyclododecane (HBCD) is one brominated flame retardant detected in human blood across the world. HBCD exposure can result in neurological problems and altered lipid metabolism, but to date the two remain unlinked. As lipids constitute ∼50% of brain dry weight, lipid metabolism plays a critical role in neuronal function and homeostasis. To determine the effect of HBCD exposure on brain lipid metabolism, young adult male C57BL/6 mice were exposed to 1 mg/kg HBCD every 3 days for 28 days. Major lipid classes were found to change across brain regions, including the membrane glycerolipids phosphatidylcholine and phosphatidylethanolamine, and sphingolipids such as hexosylceramide. In addition, saturated, monounsaturated, and polyunsaturated fatty acids were enriched within brain lipid species. To understand the source of the brain lipidomic alterations, the blood and liver lipidomes and the cecal microbiome were evaluated. The liver and blood demonstrated changes amongst multiple lipid classes, including triacylglycerol suppression, as well as altered esterified fatty acid content. Significant alterations were also detected in the cecal microbiome, with decreases in the Firmicutes to Bacteriodetes ratio, changes in beta diversity, and pathway alterations associated with metabolic pathways and amino acid biosynthesis. These data demonstrate that HBCD can induce lipidomic alterations across brain regions and organs and supports a potential role of the microbiome in these alterations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Trace minerals and vitamins are essential for optimizing feedlot cattle growth, health, and carcass characteristics. Understanding factors that influence trace mineral and vitamin absorption and metabolism is important when formulating feedlot cattle diets. Current feedlot industry supplementation practices typically exceed published trace mineral requirements by a factor of 2 to 4. Therefore, the intent of this review is to briefly discuss the functions of trace minerals and vitamins that are typically supplemented in feedlot diets and to examine the impact of dose of trace mineral or vitamin on growth performance, health, and carcass characteristics of feedlot cattle., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fifty-four multiparous beef cows with calves were used to evaluate the effects of Mo source (feed or water) on reproduction, mineral status, and performance over two cow-calf production cycles (553 days). Cows were stratified by age, body weight, liver Cu, and Mo status and were then randomly assigned to one of six treatment groups. Treatments were (1) negative control (NC; basal diet with no supplemental Mo or Cu), (2) positive control (NC + Cu; 3 mg of supplemental Cu/kg DM), (3) NC + 500 µg Mo/L from Na2MoO4·2H2O supplied in drinking water, (4) NC + 1000 µg Mo/L of Na2MoO4·2H2O supplied in drinking water, (5) NC + Mo 1000-water + 3 mg of supplemental Cu/kg DM, and (6) NC + 3.0 mg of supplemental Mo/kg diet DM from Na2MoO4·2H2O. Animals were allowed ad libitum access to both harvested grass hay (DM basis: 6.6% crude protein; 0.15% S, 6.7 mg Cu/kg, 2.4 mg Mo/kg) and water throughout the experiment. Calves were weaned at approximately 6 months of age each year. Dietary Cu concentration below 10.0 mg Cu/kg DM total diet reduced liver and plasma Cu concentrations to values indicative of a marginal Cu deficiency in beef cows. However, no production parameters measured in this experiment were affected by treatment. Results suggest that Mo supplemented in water or feed at the concentrations used in this experiment had minimal impact on Cu status and overall performance., (© 2023. The Author(s).)

Background and Aim: There is limited research on the use of histamine-H2 receptor antagonists and proton pump inhibitors for treating COVID-19. We compare clinical outcomes between patients hospitalized with COVID-19 receiving famotidine or pantoprazole., Methods: This retrospective study included 2184 patients (famotidine: n  = 638, pantoprazole: n  = 727, nonuse: n  = 819) aged 18 years or older treated for COVID-19 from March 2020 to March 2021. Patients who received both famotidine and pantoprazole treatments were excluded. Multivariate logistic regression was used for the primary outcome, namely all-cause mortality, and the secondary outcomes, namely mechanical ventilation, vasopressor use, acute kidney injury, and gastrointestinal bleeding. The main predictor variable was the use of famotidine or pantoprazole. Covariates were demographics, chronic diseases, and symptoms., Results: As compared to nonuse, famotidine (OR: 0.30, 95% CI: 0.20-0.44, P  < 0.001) and pantoprazole (OR: 0.47, 95% CI: 0.33-0.66, P  < 0.001) were significantly associated with lower odds for all-cause mortality. Comparison of famotidine and pantoprazole showed that the former had lower odds for all-cause mortality (OR: 0.65, 95% CI:0.45-0.95, P  < 0.05), mechanical ventilation (OR: 0.38, 95% CI: 0.25-0.58, P  < 0.001), vasopressor use (OR: 0.33, 95% CI: 0.22-0.48, P  < 0.001), acute kidney injury (OR: 0.40, 95% CI: 0.30-0.54, P  < 0.001), and gastrointestinal bleeding (OR: 0.15, 95% CI: 0.08, 0.29, P  < 0.001)., Conclusions: Famotidine is associated with lower odds for all-cause mortality, mechanical ventilation, vasopressor use, acute kidney injury, and gastrointestinal bleeding as compared to pantoprazole in patients hospitalized with COVID-19. We recommend that clinicians consider the use of famotidine over pantoprazole for hospitalized COVID-19 patients. Future research with a clinical trial would be beneficial to further support such use of famotidine., (© 2023 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Chemical overexposures and war-related stress during the 1990-1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to endure. These symptoms culminate into a disease known as Gulf War Illness (GWI) and affect about a third of the GW veteran population. Currently, comprehensive effective GWI treatment options are unavailable. Here, an established GWI mouse model was utilized to explore the (1) long-term behavioral and neuroinflammatory effects of deployment-related GWI chemicals exposure and (2) ability of the immunotherapeutic lacto-N-fucopentaose III (LNFPIII) to improve deficits when given months after the end of exposure. Male C57BL6/J mice (8-9 weeks old) were administered pyridostigmine bromide (PB) and DEET for 14 days along with corticosterone (CORT; latter 7 days) to emulate wartime stress. On day 15, a single injection of the nerve agent surrogate diisopropylfluorophosphate (DFP) was given. LNFPIII treatment began 7 months post GWI chemicals exposure and continued until study completion. A battery of behavioral tests for assessment of cognition/memory, mood, and motor function in rodents was performed beginning 8 months after exposure termination and was then followed by immunohistochemcal evaluation of neuroinflammation and neurogenesis. Within tests of motor function, prior GWI chemical exposure led to hyperactivity, impaired sensorimotor function, and altered gait. LNFPIII attenuated these motor-related deficits and improved overall grip strength. GWI mice also exhibited more anxiety-like behavior that was reduced by LNFPIII; this was test-specific. Short-term, but not long-term memory, was impaired by prior GWI exposure; LNFPIII improved this measure. In the brains of GWI mice, but not in mice treated with LNFPIII, glial activation was increased. Overall, it appears that months after exposure to GWI chemicals, behavioral deficits and neuroinflammation are present. Many of these deficits were attenuated by LNFPIII when treatment began long after GWI chemical exposure termination, highlighting its therapeutic potential for veterans with GWI., (© 2022 The Authors.)

High solubility of certain trace minerals (TM) in the rumen can alter nutrient digestibility and fermentation. The objectives of the present studies were to determine the effects of TM source on 1) nutrient digestibility and ruminal fermentation, 2) concentrations of soluble Cu, Zn, and Mn in the rumen following a pulse dose of TM, and 3) Cu, Zn, and Mn binding strength on ruminal digesta using dialysis against a chelating agent in steers fed a diet formulated to meet the requirements of a high producing dairy cow. Twelve Angus steers fitted with ruminal cannulae were adapted to a diet balanced with nutrient concentrations similar to a diet for a high producing lactating dairy cow for 21 d. Steers were then randomly assigned to dietary treatments consisting of 10 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either sulfate (STM), hydroxychloride (HTM) or complexed trace minerals (CTM). The experimental design did not include a negative control (no supplemental Cu, Mn, or Zn) because the basal diet did not meet the National Research Council requirement for Cu and Zn. Copper, Mn, and Zn are also generally supplemented to lactating dairy cow diets at concentrations approximating those supplied in the present study. Following a 14-d adaptation period, total fecal output was collected for 5-d. Following the fecal collection period, rumen fluid was collected for Volatile fatty acid (VFA) parameters. On the following day, the same diet was provided for 14 d, without supplemental Cu, Zn, and Mn. This period served as a wash-out period. A pulse dose of 100, 400, and 600 mg of Cu, Zn, Mn, respectively, from either STM, HTM, or CTM, was administered via ruminal cannulae to the steers on day 15. Over a 24-h period ruminal samples were obtained every 2-h. Following centrifugation, the supernatant was analyzed for Cu, Mn, and Zn. Ruminal solid digesta samples from times 0, 12, and 24 h after bolus dosing were exposed to dialysis against Tris-EDTA. Digestibility of NDF and ADF were lesser in STM vs. HTM and vs. CTM supplemented steers. Steers receiving HTM and CTM had greater total VFA concentrations than STM, and molar proportions of individual VFA were not affected by treatment. Ruminal soluble Cu and Zn concentrations were greater post dosing in STM and CTM supplemented steers at 2, 4, and 6 h for Cu and 4, 6, 8, 10 and 12 h for Zn when compared to HTM supplemented steers. The release of Cu and Zn from ruminal solid digesta following dialysis against Tris-EDTA at 12 and 24 h postdosing was greater for steers receiving HTM compared to those receiving STM or CTM. Results indicate trace mineral source impacts: 1) how tightly bound Cu and Zn are to ruminal solid digesta; 2) fiber digestion; 3) and ruminal total VFA concentrations., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Drugs of abuse, such as cocaine, produce aberrant changes in synaptic transmission and plasticity that emerge throughout withdrawal. One region of the brain that displays a high degree of synaptic plasticity, as well as connectivity with mesolimbic structures such as the nucleus accumbens, is the ventral hippocampus (vH). Here, we investigated the effects of an escalating cocaine dosing schedule on vH CA1 excitatory transmission by measuring place preference and recording excitatory postsynaptic currents (EPSCs) at three different withdrawal time points: withdrawal day (WD) 2, 9 or 28. Behaviourally, this escalating cocaine-conditioning protocol was capable of producing conditioned place preference that persisted through WD28. Physiologically, cocaine conditioning produced an increase in vH excitatory transmission on WD2 that appeared to be the result of an increase in calcium-impermeable (CI)-AMPA receptor density. Excitatory transmission was still enhanced in cocaine-treated animals on WD9; however, a significant increase in the contribution of calcium-permeable (CP)-AMPA receptors to EPSCs was detected as compared with WD2. By WD28, these CP-AMPA receptors provided a major contribution to vH CA1 excitatory transmission, resulting in synaptic responses distinct from WD2 and WD9. Taken together, these results highlight progressive changes in vH synaptic transmission during withdrawal that may enhance cocaine contextual associations., (© 2021 Society for the Study of Addiction.)

During lairage at slaughter plants, cattle can be exposed to extreme heat conditions from pen densities and holding pen microclimates. While research outlining heat mitigation strategies used in other sectors of the beef supply chain is available, there is no published data on the use of heat mitigation strategies at slaughter plants. The objective of this study was to characterize short-term heat mitigation strategies used by commercial beef slaughter plants in the United States. Twenty-one beef slaughter plants, representing an estimated 60% of beef slaughter in the United States, were included in the study. All plants indicated use of at least one heat mitigation strategy, and five of them used more than one type. Sprinklers/misters were the most commonly used heat mitigation type ( n = 17, 81%), and fans were the least common type ( n = 4, 19%). Shade usage was present in several plants ( n = 7, 33%), ranging from barn style roofs to shade cloths. Respondents indicated that they believed heat mitigation strategies provide benefits both to cattle well-being and meat quality outcomes. Future research should focus on the effectiveness of these techniques in improving animal well-being and quality outcomes in the slaughter plant environment and protocols for optimum implementation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Twelve Angus steers (BW 452.8 ± 6.1 kg) fitted with ruminal cannulae were used to determine the impact of trace mineral (TM) source on digestibility, ruminal volatile fatty acid (VFA) composition, ruminal soluble concentrations of Cu, Zn, and Mn, and relative binding strength of trace minerals located in the rumen insoluble digesta fraction. Steers were fed a medium-quality grass hay diet (DM basis: 10.8% CP, 63.1% neutral detergent fiber [NDF], 6.9 mg Cu/kg, 65.5 mg Mn/kg, and 39.4 mg Zn/kg) supplemented with protein for 21 d. Treatments consisted of either sulfate (STM) or hydroxy (HTM) sources (n = 6 steers/treatment) to provide 20, 40, and 60 mg supplemental Cu, Mn, and Zn/kg DM, respectively. Following a 21-d adaptation period, total fecal output was collected for 5 d. Dry matter (P < 0.07) and CP (P < 0.06) digestibility tended to be reduced, and NDF (P < 0.04) and acid detergent fiber (ADF) (P < 0.05) digestibility were reduced in STM- vs. HTM-supplemented steers. On day 6, ruminal fluid was collected at 0, 2, and 4 h post-feeding and analyzed for VFA. There were no treatment x time interactions for VFA. Steers receiving HTM had less (P < 0.02) molar proportions of butyric acid and greater (P < 0.05) total VFA concentrations than STM-supplemented steers. Steers were then fed the same diet without supplemental Cu, Zn, or Mn for 14 d. On day 15 steers received a pulse dose of 20 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either STM or HTM (n = 6 steers/treatment). Ruminal samples were obtained at 2-h intervals starting at -4 and ending at 24 h relative to dosing. There was a treatment x time interaction (P < 0.03) for ruminal soluble Cu, Mn, and Zn concentrations. Ruminal soluble mineral concentrations were greater (P < 0.05) for Cu at 4, 6, 8, 10, 12, and 14 h; for Mn at 4 and 6 h; and for Zn at 4, 6, and 8 h post-dosing in STM compared with HTM-supplemented steers. Copper concentrations were greater (P < 0.05) at 12 and 24 h and Zn concentrations in ruminal solid digesta were greater at 24 h in HTM-supplemented steers. Upon dialysis against Tris-EDTA, the percent Zn released from digesta was greater (P < 0.05) at 12 h (P < 0.03) and 24 h (P < 0.05), and the percent Cu released was greater (P < 0.02) at 24 h post-dosing in HTM steers when compared with STM-supplemented steers. Results indicate that Cu and Zn from HTM have low solubility in the rumen and appear to be less tightly bound to ruminal solid digesta than Cu and Zn from STM. The lower ruminal soluble concentrations of Cu and Zn in steers given HTM were associated with greater fiber digestibility., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Residual effects of the 1990-1991 Gulf War (GW) still plague veterans 30 years later as Gulf War Illness (GWI). Thought to stem mostly from deployment-related chemical overexposures, GWI is a disease with multiple neurological symptoms with likely immunological underpinnings. Currently, GWI remains untreatable, and the long-term neurological disease manifestation is not characterized fully. The present study sought to expand and evaluate the long-term implications of prior GW chemicals exposure on neurological function 6-8 months post GWI-like symptomatology induction. Additionally, the beneficial effects of delayed treatment with the glycan immunotherapeutic lacto-N-fucopentaose III (LNFPIII) were evaluated. Male C57BL/6J mice underwent a 10-day combinational exposure (i.p.) to GW chemicals, the nerve agent prophylactic pyridostigmine bromide (PB) and the insecticide permethrin (PM; 0.7 and 200 mg/kg, respectively). Beginning 4 months after PB/PM exposure, a subset of the mice were treated twice a week until study completion with LNFPIII. Evaluation of cognition/memory, motor function, and mood was performed beginning 1 month after LNFPIII treatment initiation. Prior exposure to PB/PM produced multiple locomotor, neuromuscular, and sensorimotor deficits across several motor tests. Subtle anxiety-like behavior was also present in PB/PM mice in mood tests. Further, PB/PM-exposed mice learned at a slower rate, mostly during early phases of the learning and memory tests employed. LNFPIII treatment restored or improved many of these behaviors, particularly in motor and cognition/memory domains. Electrophysiology data collected from hippocampal slices 8 months post PB/PM exposure revealed modest aberrations in basal synaptic transmission and long-term potentiation in the dorsal or ventral hippocampus that were improved by LNFPIII treatment. Immunohistochemical analysis of tyrosine hydroxylase (TH), a dopaminergic marker, did not detect major PB/PM effects along the nigrostriatal pathway, but LNFPIII increased striatal TH. Additionally, neuroinflammatory cells were increased in PB/PM mice, an effect reduced by LNFPIII. Collectively, long-term neurobehavioral and neurobiological dysfunction associated with prior PB/PM exposure was characterized; delayed LNFPIII treatment provided multiple behavioral and biological beneficial effects in the context of GWI, highlighting its potential as a GWI therapeutic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Approximately one-third of Persian Gulf War veterans are afflicted by Gulf War Illness (GWI), a chronic multisymptom condition that fundamentally presents with cognitive deficits (i.e., learning and memory impairments) and neuroimmune dysfunction (i.e., inflammation). Factors associated with GWI include overexposures to neurotoxic pesticides and nerve agent prophylactics such as permethrin (PM) and pyridostigmine bromide (PB), respectively. GWI-related neurological impairments associated with PB-PM overexposures have been recapitulated in animal models; however, there is a paucity of studies assessing PB-PM-related aberrations in hippocampal synaptic plasticity and transmission that may underlie behavioral impairments. Importantly, FDA-approved neuroactive treatments are currently unavailable for GWI. In the present study, we assessed the efficacy of an immunomodulatory therapeutic, lacto-N-fucopentaose-III (LNFPIII), on ameliorating acute effects of in vivo PB-PM exposure on synaptic plasticity and transmission as well as trophic factor/cytokine expression along the hippocampal dorsoventral axis. PB-PM exposure resulted in hippocampal synaptic transmission deficits 48 h post-exposure, a response that was ameliorated by LNFPIII coadministration, particularly in the dorsal hippocampus (dH). LNFPIII coadministration also enhanced synaptic transmission in the dH and the ventral hippocampus (vH). Notably, LNFPIII coadministration elevated long-term potentiation in the dH. Further, PB-PM exposure and LNFPIII coadministration uniquely altered key inflammatory cytokine and trophic factor production in the dH and the vH. Collectively, these findings demonstrate that PB-PM exposure impaired hippocampal synaptic responses 48 h post-exposure, impairments that differentially manifested along the dorsoventral axis. Importantly, LNFPIII ameliorated GWI-related electrophysiological deficits, a beneficial effect indicating the potential efficacy of LNFPIII for treating GWI., (Copyright © 2021. Published by Elsevier B.V.)

Aims: The present study investigated if treatment with the immunotherapeutic, lacto-N-fucopentaose-III (LNFPIII), resulted in amelioration of acute and persisting deficits in synaptic plasticity and transmission as well as trophic factor expression along the hippocampal dorsoventral axis in a mouse model of Gulf War Illness (GWI)., Main Methods: Mice received either coadministered or delayed LNFPIII treatment throughout or following, respectively, exposure to a 15-day GWI induction paradigm. Subsets of animals were subsequently sacrificed 48 h, seven months, or 11 months post GWI-related (GWIR) exposure for hippocampal qPCR or in vitro electrophysiology experiments., Key Findings: Progressively worsened impairments in hippocampal synaptic plasticity, as well as a biphasic effect on hippocampal synaptic transmission, were detected in GWIR-exposed animals. Dorsoventral-specific impairments in hippocampal synaptic responses became more pronounced over time, particularly in the dorsal hippocampus. Notably, delayed LNFPIII treatment ameliorated GWI-related aberrations in hippocampal synaptic plasticity and transmission seven and 11 months post-exposure, an effect that was consistent with enhanced hippocampal trophic factor expression and absence of increased interleukin 6 (IL-6) in animals treated with LNFPIII., Significance: Approximately a third of Gulf War Veterans have GWI; however, GWI therapeutics are presently limited to targeted and symptomatic treatments. As increasing evidence underscores the substantial role of persisting neuroimmune dysfunction in GWI, efficacious neuroactive immunotherapeutics hold substantial promise in yielding GWI remission. The findings in the present report indicate that LNFPIII may be an efficacious candidate for ameliorating persisting neurological abnormalities presented in GWI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The majority of Mo research has focused on the antagonist effect of Mo, alone or in combination with elevated dietary S, on Cu absorption and metabolism in ruminants. Diets containing both >5.0 mg of Mo/kg DM and >0.33% S have been reported to reduce the Cu status in cattle and sheep. Therefore, due to the potential for inducing Cu deficiency, Mo and S concentrations in the diet should be monitored and kept within appropriate values. Elevated sulfate concentrations in drinking water can also be detrimental to livestock production, especially in ruminants. High concentrations of sulfate in water have been extensively studied in cattle because high-sulfate water induces polioencephalomalacia in ruminants. However, little research has been conducted investigating the impact of Mo in water on Cu metabolism in ruminants. Based on the limited number of published experiments, it appears that Mo in drinking water may have a lower antagonistic impact on the Cu status in cattle when compared to Mo consumed in the diet. This response may be due to a certain percentage of water bypassing the rumen when consumed by ruminants. Therefore, the objective of this review was to examine the impact of Mo in drinking water on cattle performance and Mo and Cu metabolism.

Shade is a mechanism to reduce heat load providing cattle with an environment supportive of their welfare needs. Although heat stress has been extensively reviewed, researched, and addressed in dairy production systems, it has not been investigated in the same manner in the beef cattle supply chain. Like all animals, beef cattle are susceptible to heat stress if they are unable to dissipate heat during times of elevated ambient temperatures. There are many factors that impact heat stress susceptibility in beef cattle throughout the different supply chain sectors, many of which relate to the production system, that is, availability of shade, microclimate of environment, and nutrition management. The results from studies evaluating the effects of shade on production and welfare are difficult to compare due to variation in structural design, construction materials used, height, shape, and area of shade provided. Additionally, depending on operation location, shade may or may not be beneficial during all times of the year, which can influence the decision to make shade a permanent part of management systems. Shade has been shown to lessen the physiologic response of cattle to heat stress. Shaded cattle exhibit lower respiration rates, body temperatures, and panting scores compared with unshaded cattle in weather that increases the risk of heat stress. Results from studies investigating the provision of shade indicate that cattle seek shade in hot weather. The impact of shade on behavioral patterns is inconsistent in the current body of research, with some studies indicating that shade provision impacts behavior and other studies reporting no difference between shaded and unshaded groups. Analysis of performance and carcass characteristics across feedlot studies demonstrated that shaded cattle had increased ADG, improved feed efficiency, HCW, and dressing percentage when compared with cattle without shade. Despite the documented benefits of shade, current industry statistics, although severely limited in scope, indicate low shade implementation rates in feedlots and data in other supply chain sectors do not exist. Industry guidelines and third-party on-farm certification programs articulate the critical need for protection from extreme weather but are not consistent in providing specific recommendations and requirements. Future efforts should include: updated economic analyses of cost vs. benefit of shade implementation, exploration of producer perspectives and needs relative to shade, consideration of shade impacts in the cow-calf and slaughter plant segments of the supply chain, and integration of indicators of affective (mental) state and preference in research studies to enhance the holistic assessment of cattle welfare., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The microbiota's influence on host (patho) physiology has gained interest in the context of Gulf War Illness (GWI), a chronic disorder featuring dysregulation of the gut-brain-immune axis. This study examined short- and long-term effects of GWI-related chemicals on gut health and fecal microbiota and the potential benefits of Lacto-N-fucopentaose-III (LNFPIII) treatment in a GWI model. Male C57BL/6J mice were administered pyridostigmine bromide (PB; 0.7 mg/kg) and permethrin (PM; 200 mg/kg) for 10 days with concurrent LNFPIII treatment (35 μg/mouse) in a short-term study (12 days total) and delayed LNFPIII treatment (2×/week) beginning 4 months after 10 days of PB/PM exposure in a long-term study (9 months total). Fecal 16S rRNA sequencing was performed on all samples post-LNFPIII treatment to assess microbiota effects of GWI chemicals and acute/delayed LNFPIII administration. Although PB/PM did not affect species composition on a global scale, it affected specific taxa in both short- and long-term settings. PB/PM elicited more prominent long-term effects, notably, on the abundances of bacteria belonging to Lachnospiraceae and Ruminococcaceae families and the genus Allobaculum . LNFPIII improved a marker of gut health (i.e., decreased lipocalin-2) independent of GWI and, importantly, increased butyrate producers (e.g., Butyricoccus , Ruminococcous ) in PB/PM-treated mice, indicating a positive selection pressure for these bacteria. Multiple operational taxonomic units correlated with aberrant behavior and lipocalin-2 in PB/PM samples; LNFPIII was modulatory. Overall, significant and lasting GWI effects occurred on specific microbiota and LNFPIII treatment was beneficial.

Although there has been an increasing appreciation for functional differences between the dorsal (dH) and ventral (vH) hippocampal sectors, there is a lack of information characterizing the cholinergic and noncholinergic mechanisms of acetylcholinesterase inhibitors on synaptic transmission along the hippocampal dorsoventral axis. Diisopropylfluorophosphate (DFP) is an organophosphate (OP) that is commonly employed as a nerve agent surrogate in vitro as well as in rodent models of disease states, such as Gulf War Illness. The present study investigated the cholinergic and noncholinergic mechanisms responsible for the effects of acute DFP exposure on dH and vH synaptic transmission in a hippocampal slice preparation. A paired-pulse extracellular recording protocol was used to monitor the population spike (PS) amplitude as well as the PS paired-pulse ratio (PS-PPR) in the CA1 subfield of the dH and the vH. We observed that DFP-induced PS1 inhibition was produced by a cholinergic mechanism in the dH, whereas a noncholinergic mechanism was indispensable in mediating the inhibitory effect of DFP on the PS1 in the vH. PS-PPR in both dH and vH sectors was increased by acute DFP exposure, an effect that was blocked by an N-methyl-D-aspartate receptor antagonist but not by cholinergic antagonists. Clinical reports have indicated dorsoventral-specific hippocampal abnormalities in cases of OP intoxications. Therefore, the observed dorsoventral-specific noncholinergic mechanisms underlying the effects of DFP on hippocampal synaptic transmission may have important implications for the treatment of OP overexposures. SIGNIFICANCE STATEMENT: It is unknown if acetylcholinesterase inhibitors differentially impact dorsal and ventral hippocampal synaptic transmission. The data in the present study show that an organophosphate, diisopropylfluorophosphate, impacts glutamatergic transmission along the dorsoventral axis in a hippocampal slice preparation via distinct cholinergic and noncholinergic mechanisms. These findings may provide insight into investigations of therapeutic agents that target noncholinergic mechanisms in cases of organophosphate overexposures., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)

Gulf War Illness (GWI) manifests a multitude of symptoms, including neurological and immunological, and approximately a third of the 1990-1991 Gulf War (GW) veterans suffer from it. This study sought to characterize the acute neurochemical (monoamine) and neuroinflammatory profiles of two established GWI animal models and examine the potential modulatory effects of the novel immunotherapeutic Lacto-N-fucopentaose III (LNFPIII). In Model 1, male C57BL/6 J mice were treated for 10 days with pyridostigmine bromide (PB) and permethrin (PM). In Model 2, a separate cohort of mice were treated for 14 days with PB and N,N-Diethyl-methylbenzamide (DEET), plus corticosterone (CORT) via drinking water on days 8-14 and diisopropylfluorophosphate (DFP) on day 15. LNFPIII was administered concurrently with GWI chemicals treatments. Brain and spleen monoamines and hippocampal inflammatory marker expression were examined by, respectively, HPLC-ECD and qPCR, 6 h post treatment cessation. Serotonergic (5-HT) and dopaminergic (DA) dyshomeostasis caused by GWI chemicals was apparent in multiple brain regions, primarily in the nucleus accumbens (5-HT) and hippocampus (5-HT, DA) for both models. Splenic levels of 5-HT (both models) and norepinephrine (Model 2) were also disrupted by GWI chemicals. LNFPIII treatment prevented many of the GWI chemicals induced monoamine alterations. Hippocampal inflammatory cytokines were increased in both models, but the magnitude and spread of inflammation was greater in Model 2; LNFPIII was anti-inflammatory, more so in the apparently milder Model 1. Overall, in both models, GWI chemicals led to monoamine disbalance and neuroinflammation. LNFPIII co-treatment prevented many of these disruptions in both models, which is indicative of its promise as a potential GWI therapeutic., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Cocaine dependence affects millions of individuals worldwide; however, there are no pharmacotherapeutic and/or diagnostic solutions. Recent evidence suggests a role for lipid signaling in the development and maintenance of addiction, highlighting the need to understand how lipid remodeling mediates neuroadaptation after cocaine exposure., Methods: This study utilized shotgun lipidomics to assess cocaine-induced lipid remodeling in rats using a novel behavioral regimen that incorporated multiple sessions of extinction training and reinstatement testing., Results: Mass spectrometric imaging demonstrated widespread decreases in phospholipid (PL) abundance throughout the brain, and high-spatial resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry indicated hippocampus-specific PL alterations following cocaine exposure. We analyzed the expression of genes involved in hippocampal lipid metabolism and observed region-specific regulation. In addition, we found that cocaine exposure differentially regulates mitochondrial biogenesis in the brain., Conclusions: This work presents a comprehensive lipidomic assessment of cocaine-induced lipid remodeling in the rat brain. Further, these findings indicate a potential interplay between CNS energetics and differential lipid regulation and suggest a role for cocaine in the maintenance of energy homeostasis., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

The effects of drugs of abuse, such as cocaine, on learning and memory processes are thought to contribute to drug craving and relapse susceptibility. Using an Escalating (Esc) or Double Escalating (2x Esc) cocaine i.p. dosing schedule with the conditioned place preference (CPP) model we investigated the persisting effects of cocaine conditioning on long-term potentiation (LTP) in the CA1 region of the ventral hippocampus (vH), and spatial working memory in a radial arm maze (RAM) task. Interestingly, vH LTP was increased 4 weeks after the last injection day in animals that received only saline vehicle injections. A single pre-treatment with the kappa-opioid receptor antagonist, norbinaltorphimine (norBNI), blocks this stress-like effect of the conditioning protocol on vH LTP without altering the behavioral responses of the animals to cocaine. In animals that received the 2x Esc/norBNI cocaine conditioning, vH LTP was significantly decreased compared to those that received saline vehicle 4 weeks after the last dose. These 2x Esc/norBNI treated animals also exhibited a significant leftward shift in the stimulus-response curve of the baseline field excitatory postsynaptic potential (fEPSP) measurements. A separate group of 2x Esc/norBNI displayed an impaired ability to learn a spatial working memory RAM task compared to saline-conditioned mice following a similar 4 week abstinence period. Together, these results demonstrate that cocaine-induced alterations in synaptic transmission and LTP in the vH are associated with persisting drug-induced impairments in learning and memory performance., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Eight crossbred steers (BW 719.0 ± 65.0 kg) with ruminal and duodenal cannulae were used to examine the effect of trace mineral (TM) source on digestibility; ruminal and duodenal solubility of Cu, Zn, and Mn; and in vitro release of Cu, Zn, and Mn from the solid fraction of ruminal digesta. Experiment 1 determined the effect of TM source on DM and NDF digestibility in steers fed a corn silage and steam-flaked corn-based diet. Treatments consisted of 10 mg Cu, 20 mg Mn, and 30 mg Zn/kg DM from either sulfate TM (STM) or hydroxy TM (HTM) sources. Following a 14-d adaptation period, total fecal output was collected for 5 d. Dry matter digestibility was not affected by treatment, but NDF digestibility tended (P < 0.09) to be greater in HTM vs. STM supplemented steers. In Exp. 2, steers were fed a diet without supplemental Cu, Zn, or Mn for 19 d. Steers were then administrated a pulse dose of STM or HTM (2× the National Research Council requirements for Cu, Mn, and Zn) via the rumen fistula. Ruminal and duodenal samples were obtained at 2-h intervals starting at -4 and ending at 24 h relative to dosing. Ruminal soluble Cu and Zn concentrations were affected by treatment, time, and treatment × time. Soluble concentrations and percent soluble Cu and Zn in ruminal digesta increased (P < 0.05) above 0-h values for 10 h following dosing with STM, but not HTM. Concentrations of Cu and Zn in ruminal solid digesta were also affected by treatment, time, and treatment × time. Steers dosed with STM had greater (P < 0.05) solid digesta Cu concentrations at 2 and 4 h but lesser (P < 0.05) concentrations from 6 to 20 h post-dosing than those receiving HTM. Ruminal solid digesta Zn concentrations were greater (P < 0.05) in HTM vs. STM-dosed steers from 6 through 24 h post-dosing. Distribution of Mn in ruminal digesta was affected by TM source, but to a lesser extent than Zn and Cu. Duodenal soluble TM concentrations were variable and not affected by treatment. Binding strength of TM to ruminal solid digesta was estimated at 0, 6, and 12 h post-dosing using dialysis against chelating agents. The percentage of Cu and Zn released from ruminal solid digesta by dialysis against Tris-EDTA was greater (P < 0.05) at 12 h post-dosing from steers receiving HTM vs. STM. Results indicate that Cu and Zn from HTM have low solubility in the rumen and appear to be less tightly bound to ruminal solid digesta than Cu and Zn from STM., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Phosphatidylcholine (PC) is a primary phospholipid and major source of secondary lipid messengers and also serves as a biosynthetic precursor for other membrane phospholipids. Phosphocholine cytidylyltransferase (CCT) is the rate-limiting enzyme responsible for catalyzing the formation of PC. Changes in CCT activity have been associated with lipid dysregulation across various neurological disorders. Additionally, intermediates in PC synthesis, such as CDP-choline, have been suggested to attenuate drug craving during cocaine addiction. Recent work from our group demonstrated that cocaine exposure and conditioning alter the level of PC in the brain, specifically in the cerebellum and hippocampus. The present study examines the role of CCT expression in the brain and determines the effect of cocaine exposure on CCT expression. Immunohistochemical analysis (IHC) was performed to assess region-specific expression of CCT, including both of its isoforms; alpha (CCTα) and beta (CCTβ). IHC did not detect any staining of CCTα throughout the rat brain. In contrast, CCTβ expression was detected in the Purkinje cells of the cerebellum with decreases in expression following cocaine exposure. Collectively, these data demonstrate the region- and cell-specific localization of CCTα and CCTβ in the rat brain, as well as the altered expression of CCTβ in the cerebellum following cocaine exposure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Four hundred crossbred steers were used in a randomized complete block design to investigate the effects of supplemental Zn source and concentration, and dietary Cr on performance and carcass characteristics of feedlot steers fed a steam-flaked corn-based finishing diet. Steers were blocked by initial BW within cattle source (3 sources) and randomly assigned within block to 1 of 5 treatments. Before the initiation of the experiment, trace mineral supplement sources were analyzed for Zn and Cr. Zinc and Cr concentrations of the Zn sources were used to balance all dietary treatments to obtain correct Zn and Cr experimental doses. Treatments were the addition of: 1) 90 mg Zn/kg DM from ZnSO4 and 0.25 mg Cr/kg DM from Cr propionate (90ZS+Cr); 2) 30 mg Zn/kg DM from Zn hydroxychloride and 0.25 mg Cr/kg DM from Cr propionate (30ZH+Cr); 3) 90 mg Zn/kg DM from Zn hydroxychloride and 0.25 mg Cr/kg DM from Cr propionate (90ZH+Cr); 4) 60 mg Zn/kg DM from ZnSO4 and 30 mg Zn/kg DM from Zn methionine (90ZSM); and 5) 90 mg Zn/kg DM from Zn hydroxychloride (90ZH). Steers were individually weighed on d-2 and on 2 consecutive days at the end of the experiment. Initial liver biopsies were obtained from all steers at processing. Equal numbers of pen replicates per treatment were slaughtered at a commercial abattoir on day 162, 176, and 211; individual carcass data and final liver samples were collected. Total finishing dietary Zn and Cr concentrations were 118.4, 58.2, 114.2, 123.0, and 108.2 mg Zn/kg DM and 0.740, 0.668, 0.763, 0.767, and 0.461 mg Cr/kg DM, for treatments 1 to 5, respectively. Data were analyzed statistically using preplanned single degree of freedom contrasts. Steers receiving 90ZH+Cr had greater final BW (P < 0.04) and ADG (P < 0.03) when compared with steers receiving 90ZH. Additionally, hot carcass weight was 8.5 kg greater (P < 0.03) for 90ZH+Cr compared with 90ZH supplemented steers. Steers receiving 90ZH+Cr had greater longissimus muscle area when compared with steers receiving 90ZSM. Dry matter intake, G:F, morbidity and mortality, and all other carcass measurements were similar across treatments. These data indicate that under the conditions of this experiment, Zn source and concentration had no impact on live performance, liver Zn and Cu concentrations, and carcass characteristics. Supplemental Cr in diets containing 90 mg of supplemental Zn/kg DM from ZH improved final BW, ADG, and hot carcass weights., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This Research Communication describes an investigation of the nutritional depletion of total mixed rations (TMR) by pest birds. We hypothesized that species-specific bird depredation of TMR can alter the nutritional composition of the ration and that these changes can negatively impact the performance of dairy cows. Blackbirds selected the high energy fraction of the TMR (i.e., flaked corn) and reduced starch, crude fat and total digestible nutrients during controlled feeding experiments. For Holsteins producing 37·1 kg of milk/d, dairy production modeling illustrated that total required net energy intake (NEI) was 35·8 Mcal/d. For the reference TMR unexposed to blackbirds and the blackbird-consumed TMR, NEI supplied was 41·2 and 37·8 Mcal/d, and the resulting energy balance was 5·4 and 2·0 Mcal/d, respectively. Thus, Holsteins fed the reference and blackbird-consumed TMR were estimated to gain one body condition score in 96 and 254 d, and experience daily weight change due to reserves of 1·1 and 0·4 kg/d, respectively. We discuss these results in context of an integrated pest management program for mitigating the depredation caused by pest birds at commercial dairies.

European starlings are an invasive bird species in North America that are known to cause damage to commercial dairies through the consumption of total mixed rations (TMR) destined for dairy cows. We hypothesized that large foraging flocks of starlings alter the physical composition of TMR, and that this change may be significant enough to affect milk production. To better determine if production losses could potentially occur in commercial dairies as a consequence of feed consumption by foraging flocks of starlings, we conducted controlled feeding experiments using a TMR sourced from a commercial dairy that is chronically plagued with seasonal starling damage. European starlings selected the high-energy fraction of the TMR and reduced starch and crude fat availability. Using the dairy National Research Council production model equations, the nutritional changes measured in the controlled feeding experiments could potentially reduce the productivity of dairies. Model output suggests that for Holsteins producing 32 kg of milk/d, total required net energy intake (NE I ) was 31.5 Mcal/d. Within the reference TMR, NE I supplied was 29.3 Mcal/d, whereas within the starling-consumed TMR NE I supplied was 27.7 Mcal/d. Following our nutrition experiments, we assessed the efficacy of pelleted feed as a deterrent strategy for bird damage management in commercial dairies. Six different pelleted feed treatments of differing diameter were offered to starlings. All pellets of 0.95 cm diameter or larger inhibited starling consumption by ≥79%., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Alterations in lipid metabolism play a significant role in the pathogenesis of obesity-associated disorders, and dysregulation of the lipidome across multiple diseases has prompted research to identify novel lipids indicative of disease progression. To address the significant gap in knowledge regarding the effect of age and diet on the blood lipidome, we used shotgun lipidomics with electrospray ionization-mass spectrometry (ESI-MS). We analyzed blood lipid profiles of female C57BL/6 mice following high-fat diet (HFD) and low-fat diet (LFD) consumption for short (6weeks), long (22weeks), and prolonged (36weeks) periods. We examined endocannabinoid levels, plasma esterase activity, liver homeostasis, and indices of glucose tolerance and insulin sensitivity to compare lipid alterations with metabolic dysregulation. Multivariate analysis indicated differences in dietary blood lipid profiles with the most notable differences after 6weeks along with robust alterations due to age. HFD altered phospholipids, fatty acyls, and glycerolipids. Endocannabinoid levels were affected in an age-dependent manner, while HFD increased plasma esterase activity at all time points, with the most pronounced effect at 6weeks. HFD-consumption also altered liver mRNA levels of PPARα, PPARγ, and CD36. These findings indicate an interaction between dietary fat consumption and aging with widespread effects on the lipidome, which may provide a basis for identification of female-specific obesity- and age-related lipid biomarkers., (Copyright © 2017. Published by Elsevier B.V.)

Background: The prevalence of obesity has dramatically increased in children in the last few decades and is associated with chronic inflammatory diseases. Fat tissue produces IL-6 and TNF-α, which are stimuli for T H 17 cell differentiation. These cells are characterized by expression of the transcription factor receptor-related orphan receptor C (RORC) and by IL-17A production. In murine models, obesity has been linked with elevated T H 17 cell frequencies. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating T H 17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases., Methods: We studied peripheral blood samples from 15 overweight and 50 non-overweight children without a history of autoimmune diseases, asthma, atopic dermatitis or allergic rhinoconjunctivitis. T H 17 cells were quantified in Ionomycin stimulated peripheral blood mononuclear cells by flow cytometry using intracellular IL-17A staining. RORC- and IL-17A expressions were measured by real-time PCR., Results: We found significantly elevated T H cell frequencies in overweight children compared then on-overweight controls with 34.7 ± 1.5% of CD3 + CD4 + cells versus 25.4 ± 2.4% (mean ± SEM, p  = 0.0023), respectively. Moreover, T H cell frequencies correlated positively with body mass index ( r  = 0.42, p  = 0.0005, respectively). The relative mRNA expression of RORC ( p  = 0.013) and IL-17A ( p  = 0.014) were upregulated in overweight compared to non-overweight children., Conclusion: Childhood obesity is an independent factor that is associated with an elevated frequency of circulating T H 17 cells and higher expression of RORC- and IL-17A-mRNA after in vitro stimulation with Ionomycin. This might be due to the inflammatory activity of the fat tissue. Studies on T H 17 immunity should not only be adjusted for acute and chronic inflammatory diseases but also for overweight.

Thirty cross-bred steers (initial BW 452.0 ± 12.1 kg) were used to investigate the effects of Mo water concentration on performance, carcass characteristics, and mineral status of feedlot steers. The experimental design was a randomized complete block design. Steers were blocked by weight and then divided into 2 weight blocks each consisting of 15 steers. Steers were randomly assigned within block to one of 5 treatments (3 steers/treatment per block). Water treatments consisted of: 1) 0.0 µg/L, 2) 160 µg/L, 3) 320 µg/L, 4) 480 µg/L, and 5) 960 µg/L of supplemental Mo added as Na2MoO4 to the drinking water. Steers were housed in individual pens (steer = experimental unit) that contained individual 265 L water tanks for monitoring water intake. Steers were fed a growing diet for 28 d and then transitioned to a finishing diet. Block 1 steers were fed for a total of 151 d and block 2 steers were fed for a total of 112 d. Daily water intake was recorded for each steer. Steers were individually weighed on 2 consecutive days at the beginning and end of the experiment and interim weights and jugular blood samples were obtained every 28 d. Liver biopsies were obtained on d 0 and 84 from each steer within each block. Steers were transported to a commercial abattoir, slaughtered, and individual carcass data and liver samples were collected. Initial BW was used as a covariate for statistical analysis of data and significance was determined at P ≤ 0.05. No differences were observed for final BW (P > 0.98). Overall ADG (P > 0.91), DMI (P > 0.92), feed efficiency (P > 0.94), water intake (P > 0.40), hot carcass weight (P > 0.98), dressing percentage (P > 0.98), yield grade (P > 0.91), and marbling score (P > 0.29) did not differ across treatments. Lastly, no treatment differences were observed for liver concentrations of Cu (P > 0.93), Mo (P > 0.90) and Zn (P > 0.86) or plasma concentrations of Cu (P > 0.42), Mo (P > 0.43) and Zn (P > 0.62). These data indicate that water Mo concentration, within the range studied, had no impact on performance, mineral status, water intake, and carcass characteristics in feedlot steers.

Allowing rats extended access to cocaine self-administration is thought to recapitulate several key aspects of cocaine addiction in humans. Understanding the mechanisms that underlie drug-induced neuroadaptations that persist in the brain after protracted periods of abstinence is crucial towards the goal of developing therapeutic interventions for this disease state. We have employed both whole-cell voltage clamp and extracellular recording technique to assess changes in neurotransmission and long-term potentiation (LTP) in stratum radiatum of the CA1 region using the rat ventral hippocampal slice preparation. Rats allowed to self-administer cocaine daily, including 'long access' (6 hours) sessions, exhibited an increase in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate current ratio and enhanced excitatory transmission following 3-5 weeks of abstinence. Inhibitory transmission was also significantly decreased in long-access animals, and the AMPA/N-methyl-d-aspartate ratio measured in the absence of GABAergic blockers was greatly enhanced. We also observed a significant reduction of LTP magnitude evoked in the long-access cocaine rats. These findings suggest the presence of synergistic effects of enhanced AMPA and diminished gamma-aminobutyric acid neurotransmission under physiological conditions in the CA1 region of cocaine-taking animals, supporting the conclusion that persisting enhancement of AMPA-mediated transmission and/or inhibition of gamma-aminobutyric acid-mediated transmission promoted a chronic state of potentiation that partially occluded further LTP. This increased output from the ventral hippocampus to other limbic areas would be among the drug-induced neuroadaptations that persist following abstinence from cocaine self-administration and therefore may contribute to the disease state of addiction., (© 2015 Society for the Study of Addiction.)

Bovine respiratory disease complex (i.e., shipping fever and bacterial bronchopneumonia) is a multifaceted respiratory illness influenced by numerous environmental factors and microorganisms. Bovine respiratory disease (BRD) is just one component of BRD complex. Because BRD is moderately heritable, it may be possible to reduce the incidence of BRD through genetic selection. The objectives of this study were to determine the heritability and associative genetic relationships among immune system traits (i.e., cortisol, total IgG, IgG isotypes, and IL-8) in cattle monitored for BRD incidence. At an average of 83 d after weaning (219 d age and mean = 221.7 kg [SD 4.34]), crossbred steer calves ( = 2,869) were received at a commercial feedlot in southeastern Colorado over a 2-yr period. At receiving, jugular blood samples were collected at 212 (yr 1) and 226 d (yr 2) of age for immune trait analyses. The BRD phenotype was defined as a binomial variable (0 = no and 1 = yes) and compared with immune system traits measured at receiving (prior to illness onset). An animal identified as BRD positive exhibited ≥ 2 clinical signs (i.e., eye or nasal discharge, cough, lethargy, rapid breathing, acute interstitial pneumonia, or acute upper respiratory syndrome and/or a rectal temperature > 39.7°C). Heritability and genetic correlation estimates for categorical variable BRD, cortisol, IgG, IgG1, IgG2, and IL-8 were estimated from a sire model using ASREML. Heritability estimates were low to moderate for BRD (0.17 ± 0.08), cortisol (0.13 ± 0.05), IgG (0.15 ± 0.05), IgG1 (0.11 ± 0.05), IgG2 (0.24 ± 0.06), and IL-8 (0.30 ± 0.06). A moderate negative genetic correlation was determined between BRD and cortisol ( = -0.19 ± 0.32). Moderate positive correlations were found between BRD with IgG (0.42 ± 0.28), IgG1 (0.36 ± 0.32), and IL-8 ( = 0.26 ± 0.26). Variation in the BRD phenotype and immune system traits suggested herd health improvement may be achieved through genetic selection.

High-fat diet (HFD) induced obesity is associated not only with metabolic dysregulation, e.g., impaired glucose homeostasis and insulin sensitivity, but also with neurological dysfunction manifested with aberrant behavior and/or neurotransmitter imbalance. Most studies have examined HFD's effects predominantly in male subjects, either in the periphery or on the brain, in isolation and after a finite feeding period. In this study, we evaluated the time-course of selected metabolic, behavioral, and neurochemical effects of HFD intake in parallel and at multiple time points in female (C57BL/6) mice. Peripheral effects were evaluated at three feeding intervals (short: 5-6 weeks, long: 20-22 weeks, and prolonged: 33-36 weeks). Central effects were evaluated only after long and prolonged feeding durations; we have previously reported those effects after the short (5-6 weeks) feeding duration. Ongoing HFD feeding resulted in an obese phenotype characterized by increased visceral adiposity and, after prolonged HFD intake, an increase in liver and kidney weights. Peripherally, 5 weeks of HFD intake was sufficient to impair glucose tolerance significantly, with the deleterious effects of HFD being greater with prolonged intake. Similarly, 5 weeks of HFD consumption was sufficient to impair insulin sensitivity. However, sensitivity to insulin after prolonged HFD intake was not different between control, low-fat diet (LFD) and HFD-fed mice, most likely due to age-dependent decrease in insulin sensitivity in the LFD-fed mice. HFD intake also induced bi-phasic hepatic inflammation and it increased gut permeability. Behaviorally, prolonged intake of HFD caused mice to be hypoactive and bury fewer marbles in a marble burying task; the latter was associated with significantly impaired hippocampal serotonin homeostasis. Cognitive (short-term recognition memory) function of mice was unaffected by chronic HFD feeding. Considering our prior findings of short-term (5-6 weeks) HFD-induced central (hyperactivity/anxiety and altered ventral hippocampal neurochemistry) effects and our current results, it seems that in female mice some metabolic/inflammatory dysregulations caused by HFD, such as gut permeability, appear early and persist, whereas others, such as glucose intolerance, are exaggerated with continuous HFD feeding; behaviorally, prolonged HFD consumption mainly affects locomotor activity and anxiety-like responses, likely due to the advanced obesity phenotype; neurochemically, the serotonergic system appears to be most sensitive to continued HFD feeding., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study investigated the functional role of cyclin-dependent kinase inhibitor 1a (Cdkn1a or p21) in cocaine-induced responses using a knockout mouse model. Acute locomotor activity after cocaine administration (15 mg/kg, i.p.) was decreased in p21(-/-) mice, whereas cocaine-induced place preference was enhanced. Interestingly, κ-opioid-induced place aversion was also significantly enhanced. Concentration-dependent analysis of locomotor activity in response to cocaine demonstrated a rightward shift in the p21(-/-) mice. Pretreatment with a 5-hydroxytryptamine receptor antagonist did not alter the enhancement of cocaine-induced conditioned place preference in p21(-/-) mice, indicating a lack of involvement of serotonergic signaling in this response. Cocaine exposure increased p21 expression exclusively in the ventral sector of the hippocampus of rodents after either contingent or noncontingent drug administration. Increased p21 expression was accompanied by increased histone acetylation of the p21 promoter region in rats. Finally, increased neurogenesis in the dorsal hippocampus of p21(-/-) mice was also observed. These results show that functional loss of p21 altered the acute locomotor response to cocaine and the conditioned responses to either rewarding or aversive stimuli. Collectively, these findings demonstrate a previously unreported involvement of p21 in modulating responses to cocaine and in motivated behaviors., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Crossbred yearling steers ( = 360; 395 ± 33.1 kg initial BW) were used to evaluate the effects of dry-rolled corn (DRC) particle size in diets containing 20% wet distiller's grains plus solubles on feedlot performance, carcass characteristics, and starch digestibility. Steers were used in a randomized complete block design and allocated to 36 pens (9 pens/treatment, with 10 animals/pen). Treatments were coarse DRC (4,882 μm), medium DRC (3,760 μm), fine DRC (2,359 μm), and steam-flaked corn (0.35 kg/L; SFC). Final BW and ADG were not affected by treatment ( > 0.05). Dry matter intake was greater and G:F was lower ( < 0.05) for steers fed DRC vs. steers fed SFC. There was a linear decrease ( < 0.05) in DMI in the final 5 wk on feed with decreasing DRC particle size. Fecal starch decreased (linear, < 0.01) as DRC particle size decreased. In situ starch disappearance was lower for DRC vs. SFC ( < 0.05) and linearly increased ( < 0.05) with decreasing particle size at 8 and 24 h. Reducing DRC particle size did not influence growth performance but increased starch digestion and influenced DMI of cattle on finishing diets. No differences ( > 0.10) were observed among treatments for any of the carcass traits measured. Results indicate improved ruminal starch digestibility, reduced fecal starch concentration, and reduced DMI with decreasing DRC particle size in feedlot diets containing 20% wet distiller's grains on a DM basis.

Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3month old) 3xTg-AD mice were as impaired in the spatial working memory task as the older (8month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine exposure can induce lipid remodeling., Methods: Lipid changes in the brain tissues of rats sensitized to cocaine were determined through shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS). We also performed pairwise principal component analysis (PCA) to assess cocaine-induced changes in blood lipid profiles. Alterations in the abundance of phospholipid species were correlated with behavioral changes in the magnitude of either the initial response to the drug or locomotor sensitization., Results: Behavioral sensitization altered the relative abundance of several phospholipid species in the hippocampus and cerebellum, measured one week following the final exposure to cocaine. In contrast, relatively few effects on phospholipids in either the dorsal or the ventral striatum were observed. PCA analysis demonstrated that cocaine altered the relative abundance of several glycerophospholipid species as compared to saline-injected controls in blood. Subsequent MS/MS analysis identified some of these lipids as phosphatidylethanolamines, phosphatidylserines and phosphatidylcholines. The relative abundance of some of these phospholipid species were well-correlated (R(2) of 0.7 or higher) with either the initial response to cocaine or locomotor sensitization., Conclusion: Taken together, these data demonstrate that a cocaine-induced sensitization assay results in the remodeling of specific phospholipids in rat brain tissue in a region-specific manner and also alters the intensities of certain types of phospholipid species in rat blood. These results further suggest that such changes may serve as biomarkers to assess the neuroadaptations occurring following repeated exposure to cocaine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.

Mounting experimental evidence, predominantly from male rodents, demonstrates that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the brain. To shed additional light on the neurological consequences of HFD consumption in female rodents and to determine the relatively early impact of HFD in the likely continuum of neurological dysfunction in the context of chronic HFD intake, this study investigated effects of HFD feeding for up to 12weeks on selected behavioral, neurochemical, and electrophysiological parameters in adult female C57BL/6 mice; particular focus was placed on the ventral hippocampus (vHIP). Selected locomotor, emotional and cognitive functions were evaluated using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One week later, mice were sacrificed and brain regional neurochemical (monoamine) analysis was performed. Behaviorally naïve mice were maintained on their respective diets for an additional 5-6weeks at which time synaptic plasticity was determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited increased: (i) locomotor activity in the open field testing, (ii) mean turn time on the pole test, (iii) swimming time in the forced swim test, and (iv) number of marbles buried in the marble burying test. In contrast, the novel object recognition memory was unaffected. Mice on HFD also had decreased norepinephrine and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced by significant reductions in the paired-pulse ratio and long-term potentiation (LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced multiple behavioral alterations of mainly anxiety-like nature and impaired monoamine pathways in a brain region-specific manner, suggesting that in the female, certain behavioral domains (anxiety) and associated brain regions, i.e., the vHIP, are preferentially targeted by HFD., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Rumen bypass fat is commonly added to increase energy intake in dairy cattle. The objective of this study is to examine the addition of rumen bypass fat during finishing period on performance and carcass characteristics in grain fed steers. This study was conducted as a completely randomized block design with 126 cross-bred steer calves (initial BW 471.5 ± 7.5 kg) randomly assigned to pens with 9 steers/pen (n = 7 pens/treatment). Each pen was randomly assigned to one of two treatment groups; rumen bypass fat treatment (CCS, calcium soap of palm fatty acids) and control diet (CT, tallow). The diets were formulated to be isonitrogenous and isocaloric. Animals were fed twice daily at 110 % of the previous daily ad libitum intake. Blood from each sample was taken from the jugular vein. Muscle and adipose samples were collected from the longissimus dorsi regions. Feedlot performance and carcass characteristics were assessed. To examine adipogenic gene expression, quantitative real-time PCR was completed. Steers fed the CT had a greater level of performance for most of the parameters measured. The CT group had greater DMI (P < 0.05) and tended to have greater ADG (P < 0.10). Marbling score (P < 0.05) and quality grade (P < 0.05) were greater for steers fed the CT diet than those fed CCS. The longissimus muscle area tended to be greater (P < 0.10) in steers fed CT (87.60 cm(2)) than those fed CCS (84.88 cm(2)). The leptin mRNA expression was down-regulated (P < 0.05) in adipose tissue of steers fed a CCS when compared to those fed CT. These data suggest that calcium soap of palm fatty acids can be added to finishing diets without significant reduction in final body weight, although there may be modest reductions in marbling and quality scores.

The physiologic function of the "odd" Ab IgG4 remains enigmatic. IgG4 mediates immunotolerance, as, for example, during specific immunotherapy of allergies, but it mediates tissue damage in autoimmune pemphigus vulgaris and "IgG4-related disease." Approximately half of the circulating IgG4 molecules are bispecific owing to their unique ability to exchange half-molecules. Better understanding of the interrelation between IgG4 and IgE repertoires may yield insight into the pathogenesis of allergies and into potential novel therapies that modulate IgG4 responses. We aimed to compare the selective forces that forge the IgG4 and IgE repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified, cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were unique. Compared with previously published unique IgE transcripts from the same blood samples, the somatic mutation rate was significantly enhanced in IgG4 transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed statistical evidence of Ag-driven selection (p < 0.001). On average, the hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE transcripts (p < 0.001). IgG4 transcripts in the circulation of children with allergic asthma reflect some characteristics of classical Ag-driven B2 immune responses but display less indication of Ag selection than do IgE transcripts. Although allergen-specific IgG4 can block IgE-mediated allergen presentation and degranulation of mast cells, key factors that influence the Ag-binding properties of the Ab differ between the overall repertoires of circulating IgG4- and IgE-expressing cells., (Copyright © 2014 by The American Association of Immunologists, Inc.)