151 research outputs found

    Tibetan sheep are better able to cope with low energy intake than Small-tailed Han sheep due to lower maintenance energy requirements and higher nutrient digestibilities

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    Tibetan sheep are indigenous to the Qinghai-Tibetan Plateau (QTP) and are well-adapted to and even thrive under the harsh alpine conditions. Small-tailed Han sheep were introduced to the plateau because of their high prolificacy and are maintained mainly in feedlots. Because of their different backgrounds, we hypothesised that Tibetan and Small-tailed Han sheep would differ in their utilization of energy intake and predicted that Tibetan sheep would cope better with low energy intake than Small-tailed Han sheep. To test this prediction, we determined nutrient digestibilities, energy requirements for maintenance and blood metabolite and hormone concentrations involved in energy metabolism in these breeds. Sheep of each breed (n = 24 of each, all wethers and 1.5 years of age) were distributed randomly into one of four groups and offered ad libitum diets of different digestible energy (DE) densities: 8.21, 9.33, 10.45 and 11.57 MJ DE/kg Dry matter (DM). Following 42 d of measuring feed intake, a 1-week digestion and metabolism experiment was done. DM intakes did not differ between breeds nor among treatments but, by design, DE intake increased linearly in both breeds as dietary energy level increased (P < 0.001). The average daily gain (ADG) was significantly greater in the Tibetan than Small-tailed Han sheep (P = 0.003) and increased linearly in both breeds (P < 0.001). In addition, from the regression analysis of ADG on DE intake, daily DE maintenance requirements were lower for Tibetan than for Small-tailed Han sheep (0.41 vs 0.50 MJ/BW0.75, P < 0.05). The DE and metabolizable energy (ME) digestibilities were higher in the Tibetan than Small-tailed Han sheep (P < 0.001) and increased linearly as the energy level increased in the diet (P < 0.001). At the lowest energy treatment, Tibetan sheep when compared with Small-tailed Han sheep, had: 1) higher serum glucose and glucagon, but lower insulin concentrations (P < 0.05), which indicated a higher capacity for gluconeogenesis and ability to regulate glucose metabolism; and 2) higher non-esterified fatty acids (NEFA) and lower very low density lipoprotein (VLDL) and triglyceride (TG) concentrations (P < 0.05), which indicated a higher capacity for NEFA oxidation but lower ability for triglyceride (TG) synthesis. We concluded that our prediction was supported as these differences between breeds conferred an advantage for Tibetan over Small-tailed Han sheep to cope better with low energy diets

    Tibetan sheep have a high capacity to absorb and to regulate metabolism of SCFA in the rumen epithelium to adapt to low energy intake

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    The nutritional intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau is often under maintenance requirements, especially during the long, cold winter. However, they have adapted well and even thrive under these conditions. The aim of the present study was to gain insight into how the rumen epithelium of Tibetan sheep has adapted to the consumption of low-energy-level diets. For this purpose, we compared Tibetan and small-tailed Han sheep (n 24 of each breed, all wethers and 1 center dot 5 years of age), which were divided randomly into one of four groups and offered ad libitum diets of different digestible energy (DE) densities: 8 center dot 21, 9 center dot 33, 10 center dot 45 and 11 center dot 57 MJ DE/kg DM. The Tibetan sheep had higher rumen concentrations of total SCFA, acetate, butyrate and iso-acids but lower concentrations of propionate than small-tailed Han sheep. The Tibetan sheep had higher absorption capability of SCFA due to the greater absorption surface area and higher mRNA expression of the SCFA absorption relative genes than small-tailed Han sheep. For the metabolism of SCFA in the rumen epithelium, the small-tailed Han sheep showed higher utilisation of the ketogenesis pathway than Tibetan sheep; however, Tibetan sheep had greater regulation capacity in SCFA metabolism pathways. These differences between breeds allowed the Tibetan sheep to have greater capability of absorbing SCFA and better capacity to regulate the metabolism of SCFA, which would allow them to cope with low energy intake better than small-tailed Han sheep

    Disrupted Asymmetry of Inter- and Intra-Hemispheric Functional Connectivity at Rest in Medication-Free Obsessive-Compulsive Disorder

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    Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale–Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs

    Emerging CO2 capture systems

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    In 2005, the IPCC SRCCS recognized the large potential for developing and scaling up a wide range of emerging CO2 capture technologies that promised to deliver lower energy penalties and cost. These included new energy conversion technologies such as chemical looping and novel capture systems based on the use of solid sorbents or membrane-based separation systems. In the last 10 years, a substantial body of scientific and technical literature on these topics has been produced from a large number of R&D projects worldwide, trying to demonstrate these concepts at increasing pilot scales, test and model the performance of key components at bench scale, investigate and develop improved functional materials, optimize the full process schemes with a view to a wide range of industrial applications, and to carry out more rigorous cost studies etc. This paper presents a general and critical review of the state of the art of these emerging CO2 capture technologies paying special attention to specific process routes that have undergone a substantial increase in technical readiness level toward the large scales required by any CO2 capture system

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Sex-based differences in outcomes after severe injury: an analysis of blunt trauma patients in China

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    Abstract Background Experimental research suggests that females have a higher survival rate after trauma, although this claim is controversial. This study sought to determine the role of sex on mortality among trauma patients in China. Methods The study enrolled 1789 trauma patients who visited the Emergency Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University during 2015 and 2016. A retrospective data analysis was performed to determine sex-based differences after blunt trauma. Patients were stratified by age and injury severity (using the Injury Severity Score). Multiple logistic regression was used to analyze the association between sex and post-injury complications and mortality. Results Female trauma patients experienced a significantly lower risk of mortality than males (odds ratio, 0.931; 95% confidence interval, 0.883–0.982). This survival advantage of females was particularly notable in the ‘younger than 45 years’ age group. Sex-based differences were also found in the occurrence of life-threatening complications after trauma. Conclusion This study demonstrated that females are more likely to survival after severe blunt trauma and also have less inpatient complications than men, suggesting an important role for sex hormones after severe traumatic injury

    C−F Bond Activation Enables Synthesis of Aryl Difluoromethyl Bicyclopentanes as Benzophenone-Type Bioisosteres

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    Bioisosteric design has become an essential approach in the development of novel drug molecules. Recent advancements in synthetic methodologies have enabled the rapid adoption of this strategy into drug discovery programs. Consequently, conceptionally innovative practices would be appreciated by the medicinal chemistry community. Here we report an expeditous synthetic method for synthesizing aryl difluoromethyl bicyclopentane (ADB) as a novel bioisostere of the benzophenone core. This approach involves the merger of light-driven C−F bond activation and strain-release chemistry under the catalysis of a newly designed N-anionic-based organic photocatalyst. This defluorinative coupling methodology enables the direct conversion of a wide variety of commercially available trifluoromethylaromatic C−F bonds (more than 60 examples) into the corresponding difluoromethyl bicyclo[1.1.1]pentanes (BCP) arenes/difluoromethyl BCP boronates in a single step. The strategy can also be applied to [3.1.1]and [4.1.1]propellane systems, providing access to analogs with different geometries. Moreover, we have successfully used this protocol to rapidly prepare ADB-substituted analogs of the bioactive molecule Adiporon. Biological testing has shown that the ADB scaffold has the potential to enhance the pharmacological properties of benzophenone-type drug candidates
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