Nutritional modulation of oxidative stress in beef steers during the feedlot receiving period: A focus on transit stress

Feedlot receiving (i.e. the first 42 to 56 d after feedlot arrival) is a critical time period in the life of many beef animals. The combination of stressors (e. g. weaning, vaccination, commingling, novel pathogens and feedstuffs) experienced during feedlot receiving results in poor feed intake, decreased growth and increased susceptibility to disease. Transportation is a component of receiving period stress that is unavoidable due to the segmented nature of the beef industry. Transported cattle are subject to feed and water deprivation, psychological stress and physical exertion which may further hinder animal health and production efficiency. Therefore, investigation of strategies to mitigate the negative effects of receiving period and transit stress is warranted. The first objective of this research was to gain a more thorough understanding of how cattle biologically respond to transit stress, with an emphasis on transit-induced changes in oxidative stress biomarkers. Results from the studies presented herein have shown 1) a 10% decrease in plasma ascorbate and total antioxidant concentrations immediately post-transit, 2) a 16% increase in red blood cell lysate Mn-superoxide dismutase activity 1 d post-transit and 3) increased liver and muscle superoxide dismutase activity immediately post-transit. This research has also provided evidence that transportation of cattle stimulates tissue mobilization of energy producing substrates and elicits an inflammatory response. These biological processes can contribute to the production of reactive oxygen species and, in combination with the observed decrease in antioxidant status, result in oxidative stress and upregulation of antioxidant enzymes. Because endogenous synthesis of antioxidants requires nutrients that might otherwise be used by the animal for growth and immune function, the second objective of this research was to determine if improving antioxidant status of beef steers with nutritional supplements would increase resilience or aid in recovery from receiving period or transit stress. Increasing dietary supplementation of vitamin E, a fat-soluble antioxidant, during the receiving period linearly increased vitamin E status, but decreased concentrations of the endogenous antioxidant glutathione, likely due to a sparing effect of vitamin E. Minimal effects of supplemental vitamin E on feedlot health and performance were noted, probably because initial vitamin E status of steers was adequate and vitamin E deficiency did not develop in this 28 d study. Steers supplemented a yeast fermentation product with indirect antioxidant properties tended to have greater liver glutathione concentrations prior to a long-distance transit event and exhibited greater average daily gain for the first 30 d post-transit. In a separate study, superoxide dismutase activity and metabolites involved in the pentose phosphate pathway were increased in muscle of transported steers, suggesting the physical exertion associated with transit resulted in oxidative stress in the muscle, which could be detrimental to post-transit growth. To mitigate this response, steers were administered injectable vitamin C, a potent antioxidant found in large quantities in the muscle, immediately prior to or after a long-distance transit event. Steers administered vitamin C pre-transit had greater post-transit plasma ascorbate concentrations and exhibited greater average daily gain for the 56 d post-transit than steers that did not receive vitamin C or steers that received vitamin C after the transit event. Collectively, these data indicate nutritional strategies to improve antioxidant status are more effective in improving post-transit performance when they are adopted proactively (pre-transit) rather than retroactively (post-transit). Future research should seek to better understand the long-term implications of oxidative stress on cattle health and performance. Additionally, further refinement of the nutritional strategies utilized herein is needed to optimize dose and timing of supplementation for oxidative stress modulation

Optical Guidance System /OGS/ for rendezvous and docking Final report

Optical guidance system for Apollo rendezvous and dockin

A K-nearest clamping force classifier for bolt tightening of wind turbine hubs

A fuzzy-logic controller supporting the manufacturing of wind turbines and the bolt tightening of their hubs has been designed. The controller embeds assembly error recognition capability and detects tightening faults like misalignment, different threads, cross threads and wrong or small nuts. According to this capability, K-nearest classifiers have been implemented to cluster the output controllers into the diverse fault scenarios. Classifiers make use of the time of execution of the tightening process, the final angular position of and applied torque of the tightening tool, the resultant clamping force and possible combinations of those parameters. Two classes and five classes configurations are considered: classifiers are initially asked to discriminate between fault and no fault scenarios (e.g. two classes); then, five classes are considered according to five different fault situations (i.e. regular tightening, bolt misalignment, dissimilar threads of bolt and nut, missing nut and small bolt). Classifiers performances are estimated in terms of resubstitution and cross-validation loss. Confusion matrixes of actual and predicted classification are also evaluated for each classifier. The low computational cost of the proposed classifiers suggests directly implementing these algorithms on micro-controller and physical computing, which may be straight integrated within the tightening tool

Genome-wide association study of language performance in Alzheimer's disease

Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (p<5×10-8). Enrichment of GWAS association was identified in pathways related to nervous system development and glutamate receptor function and trafficking. Our results, which warrant further investigation in independent and larger cohorts, implicate GLI3, a developmental transcription factor involved in patterning brain structures, as a putative gene associated with language dysfunction in AD

Zinc supplementation and ractopamine hydrochloride impact gene expression of zinc transporters in finishing beef steers

Zinc is a trace mineral of interest for optimizing growth in feedlot cattle due to its roles in many physiological functions, including growth. Twenty-four Angus-cross steers (467 ± 13 kg) were used to assess the effects of supplemental Zn and ractopamine hydrochloride (RAC) on trace mineral concentrations and muscle gene expression. Four GrowSafe-equipped pens were randomly assigned to treatments (1 pen of six steers/treatment): 0 (CON), 60 (LOW), 120 (MED) or 180 (HI) mg supplemental Zn/kg DM (Availa-Zn, Zinpro). Dietary Zn treatments were initiated on d 0 and RAC supplementation (300 mg·steer·-1·d-1; Actogain45, Zoetis) began on d 53. Blood, liver and muscle (longissimus thoracis) samples were collected from all steers on d -4, 48, and 67. The LOW treatment was removed from gene expression analyses due to &lt; 3 steers being represented for 14 of 22 genes. Data were analyzed using ProcMixed of SAS with the fixed effect of treatment and steer as the experimental unit; orthogonal linear and quadratic contrast statements were used to compare treatments. On d 48 and 67, there were linear and quadratic trends for plasma Zn to be greater in Zn-supplemented steers than CON (P ≤ 0.10). On d 48, there was a tendency for a quadratic decrease on the expression of SLC30A4 (P ≤ 0.07) but no other differences due to treatment. On d 67, several genes involved in Zn transport and storage (MTA1, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A13) were decreased (P ≤ 0.08), suggesting increased growth influences intracellular Zn trafficking and demands

[(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease

Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS

Branching ratios of radiative transitions in O VI

We study the branching ratios of the allowed and forbidden radiative transitions among the first few (9) fine structure levels of O VI using relativistic coupled cluster theory. We find irregular patterns for a number of transitions with in $n$-complexes with $n\le4$. We have used the exisiting values of the allowed electric dipole ($E1$) transition as a benchmark of our theory. Good agreement with the existing values establish accuracies of not only the theoretical method but the basis function as well. In general the electric quadrupole ($E2$) transition probabilities are greater in magnitude than magnetic dipole ($M1$) transition probabilities, whereas for medium atomic transition frequencies they are of the same order of magnitude. On the other hand if the transitions involved are between two fine structure components of the same term, then the $M1$ transition probability is more probable than that of $E2$. We have analyzed these trends with physical arguments and order of magnitude estimations. The results presented here in tabular and graphical forms are compared with the available theoretical and observed data. Graphical analysis helps to understand the trends of electric and magnetic transitions for the decay channels presented here. Our calculated values of the lifetimes of the excited states are in very good agreement with the available results.Comment: Submitted to J. Phys. B, March 200

Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers

Multiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech. While altered glucose metabolism has been reported in subjects with sporadic bvFTD, it has yet to be investigated in an FTDP-17 sample of this size. In this study, eleven mutation carriers (5 males; mean age = 48.0 ± 6.9 years) and eight non-carriers (2 males; mean age = 43.7 ± 12.0 years) from a MSTD family were imaged using [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight of the MAPT intron 10 +3 mutation carriers met diagnostic criteria for bvFTD at the time of the PET scan, while three MAPT intron 10 +3 carriers were not cognitively impaired at the time of scan. Non-carriers had no clinically-relevant cognitive impairment at the time of the PET scan. Additionally, ten mutation carriers (5 males; mean age = 48.04 ± 2.1 years) and seven non-carriers (2 males; mean age 46.1 ± 4.1 years) underwent magnetic resonance imaging (MRI) which is an expanded sample size from a previous study. Seven MAPT mutation carriers met diagnostic criteria for bvFTD at the time of the MRI scan. Images were assessed on a voxel-wise basis for the effect of mutation carrier status. SPM8 was used for preprocessing and statistical analyses. Compared to non-carriers, MAPT mutation carriers showed lower [(18)F]FDG uptake bilaterally in the medial temporal lobe, and the parietal and frontal cortices. Anatomical changes were predominantly seen bilaterally in the medial temporal lobe areas which substantially overlapped with the hypometabolism findings. These anatomical and metabolic changes overlap previously described patterns of neurodegeneration in MSTD patients and are consistent with the characteristics of their cognitive dysfunction. These results suggest that neuroimaging can describe the neuropathology associated with this MAPT mutation

Tau-Mediated Nuclear Depletion and Cytoplasmic Accumulation of SFPQ in Alzheimer's and Pick's Disease

Tau dysfunction characterizes neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Here, we performed an unbiased SAGE (serial analysis of gene expression) of differentially expressed mRNAs in the amygdala of transgenic pR5 mice that express human tau carrying the P301L mutation previously identified in familial cases of FTLD. SAGE identified 29 deregulated transcripts including Sfpq that encodes a nuclear factor implicated in the splicing and regulation of gene expression. To assess the relevance for human disease we analyzed brains from AD, Pick's disease (PiD, a form of FTLD), and control cases. Strikingly, in AD and PiD, both dementias with a tau pathology, affected brain areas showed a virtually complete nuclear depletion of SFPQ in both neurons and astrocytes, along with cytoplasmic accumulation. Accordingly, neurons harboring either AD tangles or Pick bodies were also depleted of SFPQ. Immunoblot analysis of human entorhinal cortex samples revealed reduced SFPQ levels with advanced Braak stages suggesting that the SFPQ pathology may progress together with the tau pathology in AD. To determine a causal role for tau, we stably expressed both wild-type and P301L human tau in human SH-SY5Y neuroblastoma cells, an established cell culture model of tau pathology. The cells were differentiated by two independent methods, mitomycin C-mediated cell cycle arrest or neuronal differentiation with retinoic acid. Confocal microscopy revealed that SFPQ was confined to nuclei in non-transfected wild-type cells, whereas in wild-type and P301L tau over-expressing cells, irrespective of the differentiation method, it formed aggregates in the cytoplasm, suggesting that pathogenic tau drives SFPQ pathology in post-mitotic cells. Our findings add SFPQ to a growing list of transcription factors with an altered nucleo-cytoplasmic distribution under neurodegenerative conditions