This study investigated the effects of breed on the fatty acid compositions of the Longissimus thoracis et lumborum (LTL) of gilts and barrows. Although only one muscle was analyzed, the results gave ...a good indication of the effect that breed and sex may have on the fatty acid compositions of the meat. Breed exhibited a significant effect on the fatty acid composition of pigs, whereas the effects of sex were found to be minor. Higher contents of intramuscular fat (IMF), C16 : 1, C18 : 1 and monounsaturated fatty acids (MUFAs); darker color of meat; and lower cholesterol content, drip loss, C18 : 0, C18 : 2, polyunsaturated fatty acids (PUFAs), n-6 and n-6 : n-3 ratios were found in the LTL muscle of Pulawska pigs compared with Polish Landrace pigs. Meat of Pulawska pigs is especially suitable for the production of good-quality, cured and smoked loin for longer storage. Fat content was higher in barrows than in gilts, and as a consequence the IMF from barrows had higher saturated fatty acid proportions and hypercholesterolemic acids (OFAs) as well as lower C18 : 1 than that from gilts.
The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation ...(OXPHOS) deficiency on human immunity, we studied children with primary mitochondrial disease (MtD).
scRNAseq analysis of peripheral blood mononuclear cells was performed on matched children with MtD (N = 4) and controls (N = 4). To define B cell function we performed phage display immunoprecipitation sequencing on a cohort of children with MtD (N = 19) and controls (N = 16).
Via scRNAseq, we found marked reductions in select populations involved in the humoral immune response, especially antigen presenting cells, B cell and plasma populations, with sparing of T cell populations.
, a marker of bioenergetic stress, was significantly elevated in populations that were most depleted.
, a miRNA contained in the intron of
, was co-expressed. Knockdown studies of
demonstrated its role in promoting survival by modulating apoptosis. To determine the functional consequences of our findings on humoral immunity, we studied the antiviral antibody repertoire in children with MtD and controls using phage display and immunoprecipitation sequencing. Despite similar viral exposomes, MtD displayed antiviral antibodies with less robust fold changes and limited polyclonality.
Overall, we show that children with MtD display perturbations in the B cell repertoire which may impact humoral immunity and the ability to clear viral infections.
Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest-derived and oligodendroglial populations. Developmental genes often require multiple ...regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This Letter reports one of the most precise measurements to date of the antineutrino spectrum from a purely U235-fueled reactor, made with the final dataset from the PROSPECT-I detector at the High ...Flux Isotope Reactor. By extracting information from previously unused detector segments, this analysis effectively doubles the statistics of the previous PROSPECT measurement. The reconstructed energy spectrum is unfolded into antineutrino energy and compared with both the Huber-Mueller model and a spectrum from a commercial reactor burning multiple fuel isotopes. A local excess over the model is observed in the 5MeV to 7MeV energy region. Comparison of the PROSPECT results with those from commercial reactors provides new constraints on the origin of this excess, disfavoring at 2.2 and 3.2 standard deviations the hypotheses that antineutrinos from U235 are solely responsible and non-contributors to the excess observed at commercial reactors respectively.
In 1989 the National Institute of Mental Health began a collaborative effort to identify genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes 1, 6, 7, 10, 16, ...and 22 (Nurnberger et al 1997). An additional 56 bipolar families have been genotyped, and the combined sample of 153 pedigrees studied.
Three hierarchical affection status models were analyzed with 513 simple sequence repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity for five regions.
One region, on 16p13, was significant at the genome-wide
p < .05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed nominally significant linkage findings (
p ≤ .01). Conditional analysis assuming epistasis identified a significant increase in linkage at four regions. Families linked to 6q24 showed a significant increase in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and 13q21, and 16p13 and 9q21.
The findings are presented in rank order of nominal significance. Several of these regions have been previously implicated in independent studies of either bipolar disorder or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis between this locus and 9q21. Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Exercise has been shown to be effective for treating obesity and type 2 diabetes. However, the molecular mechanisms for adaptation to exercise training are not fully understood. Endoplasmic reticulum ...(ER) stress has been linked to metabolic dysfunction. Here we show that the unfolded protein response (UPR), an adaptive response pathway that maintains ER homeostasis upon luminal stress, is activated in skeletal muscle during exercise and adapts skeletal muscle to exercise training. The transcriptional coactivator PGC-1α, which regulates several exercise-associated aspects of skeletal muscle function, mediates the UPR in myotubes and skeletal muscle through coactivation of ATF6α. Efficient recovery from acute exercise is compromised in
ATF6α
−/− mice. Blocking ER-stress-related cell death via deletion of CHOP partially rescues the exercise intolerance phenotype in muscle-specific PGC-1α KO mice. These findings suggest that modulation of the UPR through PGC1α represents an alternative avenue to improve skeletal muscle function and achieve metabolic benefits.
► The UPR is activated in skeletal muscle during exercise ► PGC-1
α regulates the UPR in myotubes and skeletal muscle via coactivation of ATF6
α ► Exercise training leads to adaptation in skeletal muscle through ATF6
α-mediated UPR ► CHOP null mutation partially rescues exercise intolerance of MKO-PGC-1
α mice
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although genomic research has predominantly relied on phenotypic ascertainment of individuals affected with heritable disease, the falling costs of sequencing allow consideration of genomic ...ascertainment and reverse phenotyping (the ascertainment of individuals with specific genomic variants and subsequent evaluation of physical characteristics). In this research modality, the scientific question is inverted: investigators gather individuals with a genomic variant and test the hypothesis that there is an associated phenotype via targeted phenotypic evaluations. Genomic ascertainment research is thus a model of predictive genomic medicine and genomic screening. Here, we provide our experience implementing this research method. We describe the infrastructure we developed to perform reverse phenotyping studies, including aggregating a super-cohort of sequenced individuals who consented to recontact for genomic ascertainment research. We assessed 13 studies completed at the National Institutes of Health (NIH) that piloted our reverse phenotyping approach. The studies can be broadly categorized as (1) facilitating novel genotype-disease associations, (2) expanding the phenotypic spectra, or (3) demonstrating ex vivo functional mechanisms of disease. We highlight three examples of reverse phenotyping studies in detail and describe how using a targeted reverse phenotyping approach (as opposed to phenotypic ascertainment or clinical informatics approaches) was crucial to the conclusions reached. Finally, we propose a framework and address challenges to building collaborative genomic ascertainment research programs at other institutions. Our goal is for more researchers to take advantage of this approach, which will expand our understanding of the predictive capability of genomic medicine and increase the opportunity to mitigate genomic disease.
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Phenotypic ascertainment and clinical informatics methods may inadvertently limit our understanding of the full phenotypic spectrum of a genetic condition. Recruiting individuals by genotype followed by deep phenotyping may expand our understanding of genotype-disease associations. We successfully tested this approach and outline how other institutions can replicate this model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper presents an energy calibration scheme for an upgraded reactor antineutrino detector for the Precision Reactor Oscillation and Spectrum Experiment (PROSPECT). The PROSPECT collaboration is ...preparing an upgraded detector, PROSPECT-II (P-II), to advance capabilities for the investigation of fundamental neutrino physics, fission processes and associated reactor neutrino flux, and nuclear security applications. P-II will expand the statistical power of the original PROSPECT (P-I) dataset by at least an order of magnitude. The new design builds upon previous P-I design and focuses on improving the detector robustness and long-term stability to enable multi-year operation at one or more sites. The new design optimizes the fiducial volume by elimination of dead space previously occupied by internal calibration channels, which in turn necessitates the external deployment. In this paper, we describe a calibration strategy for P-II. The expected performance of externally deployed calibration sources is evaluated using P-I data and a well-benchmarked simulation package by varying detector segmentation configurations in the analysis. The proposed external calibration scheme delivers a compatible energy scale model and achieves comparable performance with the inclusion of an additional AmBe neutron source, in comparison to the previous internal arrangement. Most importantly, the estimated uncertainty contribution from the external energy scale calibration model meets the precision requirements of the P-II experiment.
GPAT1 gene is considered to be a genetic marker for intramuscular fat content. The GPAT enzymes catalyze the first step in triacylglycerol synthesis. In the present study, the search for ...polymorphisms within the pig GPAT1 gene locus as well as association analyses between SNPs and meat quality traits were performed. The association analysis demonstrated that g.133513422C > T polymorphism affected IMF content in LL, SEMI post-mortem pH and shear force of cooked LL (p ≤ .05). While the association of g.133476803 T > C polymorphism was shown concerning IMF content, meat color (L*), shear force and energy of raw meat as well as some meat texture parameters (hardness, springiness, chewiness) (p ≤ .05). The g.133476733C > T SNP was significantly associated with LL 24 h post-mortem pH, raw meat toughness and TPA hardness and chewiness (p ≤ .05). The obtained results are promising but to confirm if the GPAT1 gene can be considered to be a genetic marker for improving the quality of pork, further research is required.
•pig GPAT1 gene is highly polymorphic.•SNPs in GPAT1 locus are associated with pork quality traits, including IMF content.•SNPs in GPAT1 gene also affect some of the meat texture parameters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The relationship between adiposity and cardiovascular disease morbidity and mortality is complex. One pathway through which adiposity may influence future health outcomes is by altering how ...biological systems respond to stress. The current study aimed to examine the association between two metrics of adiposity (body mass index and waist‐hip ratio) and two indices of cardiovascular stress responses (reactivity and habituation). A sample of 455 participants (Mean age = 19.47, SD = 1.25 years; BMI = 24.32, SD = 5.04 kg/m2; 62% female; 17.9% Hispanic/Latino; 65.2% White, 18.7% Asian, 7.9% Black, 0.2% American Indian/Alaska Native, and 7% other) completed two acute psychosocial stress tasks. Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded throughout each stressor. In unadjusted and adjusted models, there were no statistically significant associations between adiposity and HR, SBP, or DBP stress reactivity or habituation. The current data do not support the hypothesis that adiposity influences health by altering cardiovascular responses to acute psychological stress. Results are at odds with prior population‐level studies and the single prior study examining adiposity and habituation. At the same time, results are in line with mounting evidence that adiposity itself does not drive poor cardiovascular outcomes seen in people classified as overweight or obese.
In a sample of young adults, we found no evidence that adiposity was related to cardiovascular stress reactivity or cardiovascular habituation to repeated stress exposure. Our research adds to a growing body of literature suggesting adiposity in itself is not a risk factor for poor cardiovascular outcomes.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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