- 作者列表："Ji QM","Xin JW","Chai ZX","Zhang CF","Dawa Y","Luo S","Zhang Q","Pingcuo Z","Peng MS","Zhu Y","Cao HW","Wang H","Han JL","Zhong JC
:Yak is an important livestock animal for the people indigenous to the harsh, oxygen-limited Qinghai-Tibetan Plateau and Hindu Kush ranges of the Himalayas. The yak genome was sequenced in 2012, but its assembly was fragmented because of the inherent limitations of the Illumina sequencing technology used to analyse it. An accurate and complete reference genome is essential for the study of genetic variations in this species. Long-read sequences are more complete than their short-read counterparts and have been successfully applied towards high-quality genome assembly for various species. In this study, we present a high-quality chromosome-scale yak genome assembly (BosGru_PB_v1.0) constructed with long-read sequencing and chromatin interaction technologies. Compared to an existing yak genome assembly (BosGru_v2.0), BosGru_PB_v1.0 shows substantially improved chromosome sequence continuity, reduced repetitive structure ambiguity, and gene model completeness. To characterize genetic variation in yak, we generated de novo genome assemblies based on Illumina short reads for seven recognized domestic yak breeds in Tibet and Sichuan and one wild yak from Hoh Xil. We compared these eight assemblies to the BosGru_PB_v1.0 genome, obtained a comprehensive map of yak genetic diversity at the whole-genome level, and identified several protein-coding genes absent from the BosGru_PB_v1.0 assembly. Despite the genetic bottleneck experienced by wild yak, their diversity was nonetheless higher than that of domestic yak. Here, we identified breed-specific sequences and genes by whole-genome alignment, which may facilitate yak breed identification.
牦牛是严酷的、氧气有限的青藏高原和喜马拉雅山兴都库什山脉当地人民的重要家畜。牦牛基因组在2012年进行了测序，但由于用于分析它的Illumina测序技术的固有局限性，其组装被碎片化。准确和完整的参考基因组对于该物种的遗传变异研究至关重要。长读序列比它们的短读序列更完整，并且已经成功地应用于各种物种的高质量基因组组装。在这项研究中，我们提出了一个高质量的染色体规模牦牛基因组组装 (BosGru_PB_v1.0) 与长读测序和染色质相互作用技术构建。与现有牦牛基因组组装 (BosGru_v2.0) 相比，BosGru_PB_v1.0表现出显著改善的染色体序列连续性、降低的重复结构模糊性和基因模型完整性。为了表征牦牛的遗传变异，我们基于Illumina短读产生了西藏和四川7个公认的国内牦牛品种和一个来自可可西里的野牦牛的从头基因组组装。我们将这8个组装体与BosGru_PB_v1.0基因组进行了比较，在全基因组水平上获得了牦牛遗传多样性的综合图谱，并鉴定了BosGru_PB_v1.0组装体中缺失的几个蛋白编码基因。尽管野牦牛经历了遗传瓶颈，但其多样性仍高于国内牦牛。在此，我们通过全基因组比对鉴定了品种特异性序列和基因，这可能有助于牦牛品种鉴定。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.