36 research outputs found
Comparison of feeding diets diluted with sorghum-sudangrass silage or low-quality grass on nutrient intake and digestibility and growth performance of Holstein dairy heifers
This study was carried out to evaluate the nutrient intakes and growth of dairy heifers offered an alfalfa silage– corn silage diet (CON; 14.3% crude protein, 61.1% total digestible nutrients, 47.9% neutral detergent fiber) compared with diets containing 1 of 2 types of sorghumsudangrass (SS) silages: conventional or photoperiod sensitive. The objective of the study was to determine the potential to use SS to control dry matter (DM) and nutrient intakes and weight gain. Both diets were similar in nutrient composition, with approximately 13% crude protein, 60 to 61% total digestible nutrients, and 55% neutral detergent fiber. Seventy-two Holstein heifers (16–18 mo at study initiation) were blocked by initial body weight (light = 422 ± 12.8 kg; medium = 455 ± 14.8 kg; heavy = 489 ± 16.7 kg) with 3 pens assigned to each weight block (8 heifers/pen; 24 heifers/block). The 3 diets were randomly allocated to the pens within each block and offered for 12 wk. Heifers offered the CON diet had greater DM, protein, and energy intakes compared with those offered the SS silage-based diets due to the greater neutral detergent fiber concentration of the SS diets. With lower DM and nutrient intakes, average daily gain was in the recommended range (0.8– 1 kg/d for Holstein heifers) for heifers offered the SS silage-based diets (mean of 0.92 kg/d for both SS diets vs. 1.11 kg/d for CON). Sorting behaviors for heifers offered both SS diets were more aggressive against long, medium, and short particles compared with those of heifers offered the CON diet; however, heifers sorted large particles from photoperiod-sensitive silage more aggressively than those from conventional silage. Based on this study, SS silage-based diets can control the DM and energy intakes for heifers and maintain optimum growth rates, with harvesting at a shorter chop length likely helping to alleviate sorting issues
Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques
Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches
Self-productivity and complementarities in human development : evidence from MARS
This paper investigates the role of self-productivity and home resources in capability formation from infancy to adolescence. In addition, we study the complementarities between basic cognitive, motor and noncognitive abilities and social as well as academic achievement. Our data are taken from the Mannheim Study of Children at Risk (MARS), an epidemiological cohort study following the long-term outcome of early risk factors. Results indicate that initial risk conditions cumulate and that differences in basic abilities increase during development. Self-productivity rises in the developmental process and complementarities are evident. Noncognitive abilities promote cognitive abilities and social achievement. There is remarkable stability in the distribution of the economic and socio-emotional home resources during the early life cycle. This is presumably a major reason for the evolution of inequality in human development
Phylogenomics of the Reproductive Parasite Wolbachia pipientis wMel: A Streamlined Genome Overrun by Mobile Genetic Elements
The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the α-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel–D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections
Comparison of feeding diets diluted with sorghum-sudangrass silage or low-quality grass on nutrient intake and digestibility and growth performance of Holstein dairy heifers
This study was carried out to evaluate the nutrient intakes and growth of dairy heifers offered an alfalfa silage– corn silage diet (CON; 14.3% crude protein, 61.1% total digestible nutrients, 47.9% neutral detergent fiber) compared with diets containing 1 of 2 types of sorghumsudangrass (SS) silages: conventional or photoperiod sensitive. The objective of the study was to determine the potential to use SS to control dry matter (DM) and nutrient intakes and weight gain. Both diets were similar in nutrient composition, with approximately 13% crude protein, 60 to 61% total digestible nutrients, and 55% neutral detergent fiber. Seventy-two Holstein heifers (16–18 mo at study initiation) were blocked by initial body weight (light = 422 ± 12.8 kg; medium = 455 ± 14.8 kg; heavy = 489 ± 16.7 kg) with 3 pens assigned to each weight block (8 heifers/pen; 24 heifers/block). The 3 diets were randomly allocated to the pens within each block and offered for 12 wk. Heifers offered the CON diet had greater DM, protein, and energy intakes compared with those offered the SS silage-based diets due to the greater neutral detergent fiber concentration of the SS diets. With lower DM and nutrient intakes, average daily gain was in the recommended range (0.8– 1 kg/d for Holstein heifers) for heifers offered the SS silage-based diets (mean of 0.92 kg/d for both SS diets vs. 1.11 kg/d for CON). Sorting behaviors for heifers offered both SS diets were more aggressive against long, medium, and short particles compared with those of heifers offered the CON diet; however, heifers sorted large particles from photoperiod-sensitive silage more aggressively than those from conventional silage. Based on this study, SS silage-based diets can control the DM and energy intakes for heifers and maintain optimum growth rates, with harvesting at a shorter chop length likely helping to alleviate sorting issues
Neprilysin inhibition in mouse islets enhances insulin secretion in a GLP-1 receptor dependent manner.
peer reviewedNeprilysin, a widely expressed peptidase upregulated in type 2 diabetes, is capable of cleaving and inactivating the insulinotropic glucagon-like peptide-1 (GLP-1). Like dipeptidyl peptidase-4 (DPP-4), inhibition of neprilysin activity under diabetic conditions is associated with increased active GLP-1 levels and improved glycemic control. While neprilysin expression has been demonstrated in islets, its local contribution to GLP-1-mediated insulin secretion remains unknown. We investigated in vitro whether islet neprilysin inhibition enhances insulin secretion in response to glucose and/or exogenous GLP-1, and whether these effects are mediated by GLP-1 receptor (GLP-1R). Further, we compared the effect of neprilysin versus DPP-4 inhibition on insulin secretion. Isolated islets from wild-type (Glp1r(+/+)) and GLP-1 receptor knockout (Glp1r(-/-)) mice were incubated with or without the neprilysin inhibitor thiorphan and/or the DPP-4 inhibitor sitagliptin for 2.5 hours. During the last hour, insulin secretion was assessed in response to 2.8 mmol/l or 20 mmol/l glucose alone or plus exogenous active GLP-1. In Glp1r(+/+) islets, neprilysin inhibition enhanced 2.8 mmol/l and 20 mmol/l glucose- and GLP-1-mediated insulin secretion to the same extent as DPP-4 inhibition. These effects were blunted in Glp1r(-/-) islets. In conclusion, inhibition of islet neprilysin in vitro increases glucose-mediated insulin secretion in a GLP-1R-dependent manner and enhances the insulinotropic effect of exogenous active GLP-1. Thus, neprilysin inhibitors may have therapeutic potential in type 2 diabetes by preserving islet-derived and circulating active GLP-1 levels
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Age is Associated with Dampened Circadian Patterns of Rest and Activity: The Study of Muscle, Mobility and Aging (SOMMA)
BackgroundThe effects of aging on circadian patterns of behavior are insufficiently described. To address this, we characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults both overall, and in relation, to sociodemographic characteristics.MethodsWe examined cross-sectional associations between RAR and age, sex, race, education, multimorbidity burden, financial, work, martial, health, and smoking status using assessments of older adults with wrist-worn free-living actigraphy data (N=820, Age=76.4 yrs, 58.2% women) participating in the Study of Muscle, Mobility and Aging (SOMMA). RAR parameters were determined by mapping an extension to the traditional cosine curve to activity data. Functional principal component analysis determined variables accounting for variance.ResultsAge was associated with several metrics of dampened RAR; women had stronger and more robust RAR vs. men (all P < 0.05). Total activity (56%) and time of activity (20%) accounted for most the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (P <0.001). Compared to the latest decile of acrophase, those in the earliest and midrange categories had more total activity (P=0.02). Being in a married-like relationship and a more stable financial situation were associated with stronger rhythms; higher education was associated with less rhythm strength (all P < 0.05).ConclusionsOlder age was associated with dampened circadian behavior; behaviors were sexually dimorphic. Some sociodemographic characteristics were associated with circadian behavior. We identified a behavioral phenotype characterized by early time-of-day of peak activity, high rhythmic amplitude, and more total activity
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Age is Associated with Dampened Circadian Patterns of Rest and Activity: The Study of Muscle, Mobility and Aging (SOMMA)
BACKGROUND: Aging is associated with declines in circadian functions. The effects of aging on circadian patterns of behavior are insufficiently described. We characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults, both overall, and in relation, to sociodemographic characteristics. METHODS: We analyzed baseline assessments of older adults with wrist-worn free-living wrist-worn actigraphy data (N=820, Age=76.4 yrs, 58.2% women) participating in the Study of Muscle, Mobility and Aging (SOMMA). We applied an extension to the traditional cosine curve to map RAR to activity data, calculating the parameters: rhythmic strength (amplitude); robustness (pseudo-F statistic); and timing of peak activity (acrophase). We also used function principal component analysis to determine 4 components describing underlying patterns of activity accounting for RAR variance. Linear models were used to examine associations between RAR and sociodemographic variables. RESULTS: Age was associated with several metrics of dampened RAR; women had stronger and more robust RAR metrics vs. men (all P < 0.05). Total activity (56%) and time of activity (20%) accounted for most the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (P <0.001). Compared to the latest decile of acrophase, those is the earliest and midrange categories had more total activity (P=0.02). RAR was associated with some sociodemographic variables. CONCLUSIONS: Older age was associated with dampened circadian behavior; and behaviors were sexually dimorphic. We identified a behavioral phenotype characterized by early time-of-day of peak activity, high rhythmic amplitude, and more total activity
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Higher expression of denervation‐responsive genes is negatively associated with muscle volume and performance traits in the study of muscle, mobility, and aging (SOMMA)
With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility, and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation-responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation-responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO2peak), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calciumdependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (CHRNA1, CHRND, CHRNE), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation-responsive genes, respectively. In conclusion, the abundance of denervationresponsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age