Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer

While intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450K in a series of regenerative nodules from within single patient livers. Bioinformatics strategies were used to ascertain within-patient heterogeneity, link epigenetic changes to clinical features, and determine their relevance to disease pathogenesis. Our data demonstrate that DNA methylation and copy number alterations evolve during the pre-neoplastic phase of HCC and independently segregate regenerative nodules into distinct clusters. Regenerative nodules with a high frequency of epigenetic changes have significantly lower copy number variation, suggesting that individual nodules have differential enrichment of epigenetic and genetic components, with both contributing to disease progression. Regenerative nodules were scored based on ‘epigenetic progression’ with higher scores associated with increased proliferation measured by Ki67 staining. Early events observed in epigenetically ‘aggressive’ nodules are enriched for genes involved in liver cancer. Our study demonstrates that marked epigenetic and genetic heterogeneity exists in early pre-neoplastic liver tissue within individual patients, emphasizing the potential contributions of each mechanism to driving liver disease progression, and it unveils strategies for identifying epigenetic drivers of hepatocellular carcinoma.     

不同光质补光对促早栽培‘瑞都香玉’葡萄果实品质的影响

以4年生‘贝达’嫁接的早熟葡萄品种‘瑞都香玉’为试材,研究设施促早栽培条件下,紫外光、蓝光和红蓝光不同光质补光对果实品质的影响,结果表明: 促早栽培节能日光温室内环境属于典型的弱蓝紫光和弱紫外光环境.与对照(未补光)相比,夜间6 h的蓝光和紫外光补光处理可显著加快葡萄果实发育过程中质量和果粒纵横径的增大、果实糖含量的升高以及酸含量的下降,红蓝光效果不明显.果实成熟期紫外光补光处理果实的单粒质量最高,蓝光与红蓝光处理显著高于对照;蓝光补光处理果实葡萄糖、果糖和总糖含量最高,紫外光次之,红蓝光略高于对照.与对照相比,蓝光补光处理可显著加快果实中里那醇、α-萜品醇、橙花醇等萜烯类组分含量高峰的出现,而紫外光、红蓝光补光处理差异较小.果实成熟期蓝光补光处理果实中里那醇、香茅醇等萜烯类物质含量最高,紫外光补光处理里那醇含量较高,香叶醇、己醛、E-2-己烯醛等主要香气物质的含量最高,而红蓝光补光处理里那醇的含量与对照相比有所降低.紫外光、蓝光和红蓝光3种光质补光处理均增加了果实中醛酮类物质的种类及含量.表明蓝光补光处理果实发育最快,成熟最早,糖含量最高,里那醇等萜烯类物质含量高峰出现的时间最早;紫外光补光处理果实的单粒质量最大,主要萜烯类组分含量高;红蓝光补光处理对改善果实品质的效果不明显.     

超敏C反应蛋白与阵发性房颤射频消融术后早期复发的关系

目的：前瞻性研究超敏C反应蛋白（hsCRP）与阵发性心房颤动射频消融术后早期复发的关系。方法：接受CARTO指导房颤射频消融术的非瓣膜性阵发性房颤患者57例,平均年龄（53.32±9.98）岁,其中男42例,女15例。术前及术后5 d连续测定外周血hsCRP和高敏肌钙蛋白T （hs-cTnT）水平,记录体表心电图,行24 h动态心电图检查。术后5 d内,32名患者（56.14%）为窦性心律,为未复发组,25名（43.86%）复发房颤,为复发组。结果：未复发组与复发组患者的hsCRP与hs-cTnT日均升高量显著正相关,P=0.044,r=0.268。而两组间基线临床特征、手术前后血浆hsCRP、hs-cTnT水平、血浆hsCRP及hs-cTnT的总升高量（峰值水平-术前水平）、日均升高量（总升高量/达到峰值所用天数）无明显统计学差异（P均>0.05）。结论：房颤射频消融术后hsCRP升高变化与心肌损伤程度相关,与早期复发无直接关系,尚不能作为预测房颤术后早期复发的高危因子。     

Interactive effects of biochar and an organic dust suppressant for revegetation and erosion control with herbaceous seed mixtures and willow cuttings

Land reclamation efforts on “non‐soil” substrates frequently involve additions of organic material coupled with soil‐stabilizing dust suppressants to control erosion, but formal experiments, particularly of interactive effects, are lacking. We examined the effects of Entac?, a tall oil pitch emulsion, and pyrolyzed wood waste‐derived biochar on early plant establishment, growth, and survivorship, in 2 factorial greenhouse experiments: 1 using a seed mix widely used for roadside erosion control (the grasses Festuca rubra, Poa pratensis, Lolium perenne, and white clover [Trifolium repens]) and 1 using rooted cuttings of sand bar willow (Salix exigua). Biochar additions of 5, 10, and 20 t/ha enhanced biomass of clover by 14–250%, but had no significant effects on grasses. Entac additions inhibited early establishment and growth of both clover and grasses at all biochar treatment levels. Entac plus biochar treatments significantly enhanced survivorship of willows following a drought treatment in a greenhouse trial. In a field trial, Entac treatments had positive effects on willow diameter growth. Collectively, these results suggest that better soil moisture retention is the principal mechanism responsible for enhanced survivorship and growth of planted willows treated with Entac and biochar on sand substrates. Given Entac's inhibitive effects on early establishment of herbaceous species, and the abilities of Entac and biochar in combination to mitigate drought stress, these treatments may be particularly well suited for ecological restoration efforts using planted tree stock on coarse‐textured substrates and where exposure and ingress of non‐native herbaceous species are of concern.     

Fish-otoliths from the early Miocene of the Castillo Formation,Venezuela: a view into the proto-Caribbean teleostean assemblages

We describe the otolith assemblage from the early Miocene (Burdigalian) exposures of the Castillo Formation at the Cerro La Cruz locality (Falcón Basin, Lara State, northwestern Venezuela). The samples were obtained through surface and bulk sampling at distinct stratigraphic levels of the study area. The otolith assemblage from Cerro La Cruz includes 14 families, 25 genera and 30 taxa, of which 20 are reported for first time from the Castillo Formation. These include two new sciaenid taxa, Ctenosciaena angusticaudata nov. sp. and Pareques laraensis nov. sp. The Castillo Formation otolith assemblage represent fishes typical of shallow and near-shore and coral reef associated environments as characterized primarily by a high taxonomic diversity and abundance of Sciaenidae, and the lack of mesopelagic families (Myctophidae). The faunal composition of Cerro La Cruz is similar to other chronological equivalent sedimentary units along the proto-Caribbean area (Pirabas and Cantaure formations; Brazil and Venezuela respectively), though the Castillo Formation fish fauna shows lower taxonomic diversity, suggesting some heterogeneity of the coastal and near shore marine environments along the southern portion of the proto-Caribbean.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:B79F51B8-BC35-4119-8957-84544286868D     

Development of spiroguanidine-derived α7 neuronal nicotinic receptor partial agonists

We describe the synthesis of quinuclidine-containing spiroguanidines and their utility as α7 neuronal nicotinic acetylcholine receptor (nAChR) partial agonists. The convergent synthetic route developed for this study allowed for rapid SAR investigation and provided access to a structurally diverse set of analogs. A potent and selective α7 nAChR partial agonist, N‐(6‐methyl‐1,3‐benzoxazol‐2‐yl)‐3′,5′‐dihydro‐4‐azaspiro[bicyclo[2.2.2]octane‐2,4′‐imidazole]‐2′‐amine (BMS-910731, 16), was identified. This compound induced immediate early genes c-fos and Arc in a preclinical rodent model of α7 nAChR-derived cellular activation and plasticity. Importantly, the ability to incorporate selectivity for the α7 nACh receptor over the 5-HT_3A receptor in this series suggested a significant difference in steric requirements between the two receptors.     

Effects of developmental conditions on growth,stress and telomeres in black‐legged kittiwake chicks

Early‐life conditions can drive ageing patterns and life history strategies throughout the lifespan. Certain social, genetic and nutritional developmental conditions are more likely to produce high‐quality offspring: those with good likelihood of recruitment and productivity. Here, we call such conditions “favoured states” and explore their relationship with physiological variables during development in a long‐lived seabird, the black‐legged kittiwake (Rissa tridactyla). Two favoured states were experimentally generated by manipulation of food availability and brood size, while hatching order and sex were also explored as naturally generating favoured states. Thus, the favoured states we explored were high food availability, lower levels of sibling competition, hatching first and male sex. We tested the effects of favoured developmental conditions on growth, stress, telomere length (a molecular marker associated with lifespan) and nestling survival. Generation of favoured states through manipulation of both the nutritional and social environments furthered our understanding of their relative contributions to development and phenotype: increased food availability led to larger body size, reduced stress and higher antioxidant status, while lower sibling competition (social environment) led to lower telomere loss and longer telomere lengths in fledglings. Telomere length predicted nestling survival, and wing growth was also positively correlated with telomere length, supporting the idea that telomeres may indicate individual quality, mediated by favoured states.     

鸡快慢羽性状遗传学基础分析综合实验探索与实践

随着全国“卓越农林人才教育培养计划”的开展,我校动物科学专业设置了“卓越班”,以突出培养学生的系统思维和创新创业能力为目标开展了系列教育教学管理和课程改革。为此,我们以“鸡快、慢羽性状”为实验对象,设计了“鸡快慢羽性状遗传学基础分析”综合实验,突出培养学生用理论知识解决生产实践问题的思维和能力。本文重点介绍了该实验作为动物遗传学实验教学案例的实施过程及效果,首先从鸡的表型观察逐步深入到遗传学基础分析,利用遗传学理论指导鸡快、慢羽品系培育的育种实践。实验内容涉及伴性遗传规律和性别决定机制等遗传学理论知识,同时还涉及基因组DNA提取、基因扩增、酶切及电泳分析等一系列分子遗传学的技术方法。不仅有利于学生综合分析能力和专业技能的掌握,还有助于培养学生对动物科学专业的科研兴趣和创新意识。此综合性实验还展现了用遗传学理论指导动物品种培育实践过程,符合动物科学专业复合应用型人才培养目标的要求,其中的教学理念和方法可推广应用于其他生物学实验教学。     

番茄果实早期发育的分子生理机制研究进展

番茄(Solanum lycopersicum)是目前世界上种植面积最广且最受欢迎的蔬菜作物之一, 也是肉果及茄科的重要模式植物。番茄果实发育主要分为早期果实发育和果实成熟2个时期, 但果实形态结构和大小主要决定于早期果实发育时期。该文围绕番茄早期果实发育时期植物激素、细胞周期、表观遗传和源库代谢等多方面调控的分子机制进行了综述, 旨在认识植物生长与发育的基本生物学问题及促进基础理论研究成果在生产中应用。     

Genomics in space life sciences

Since the early days of manned spaceflight, hazardous effects of the space environment on living organisms have been disputed. With the continuous manning of the International Space Station, the planned Chinese space station, and renewed interest in returning to the Moon and sending manned flights to Mars, identifying and addressing the potential outcomes of long-term space exposures is critically important.