Transgenerational Effects of Di(2-Ethylhexyl) Phthalate on Anogenital Distance,Sperm Functions and DNA Methylation in Rat Offspring

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.     

Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents

The phosphorylation of serine 10 in histone 3 (p-S10H3) has recently been demonstrated to participate in spinal nociceptive processing. However, superficial dorsal horn (SDH) neurons involved in p-S10H3-mediated nociception have not been fully characterized. In the present work, we combined immunohistochemistry, in situ hybridization with the retrograde labeling of projection neurons to reveal the subset of dorsal horn neurons presenting an elevated level of p-S10H3 in response to noxious heat (60 °C), causing burn injury. Projection neurons only represented a small percentage (5%) of p-S10H3-positive cells, while the greater part of them belonged to excitatory SDH interneurons. The combined immunolabeling of p-S10H3 with markers of already established interneuronal classes of the SDH revealed that the largest subset of neurons with burn injury-induced p-S10H3 expression was dynorphin immunopositive in mice. Furthermore, the majority of p-S10H3-expressing dynorphinergic neurons proved to be excitatory, as they lacked Pax-2 and showed Lmx1b-immunopositivity. Thus, we showed that neurochemically heterogeneous SDH neurons exhibit the upregulation of p-S10H3 shortly after noxious heat-induced burn injury and consequential tissue damage, and that a dedicated subset of excitatory dynorphinergic neurons is likely a key player in the development of central sensitization via the p-S10H3 mediated pathway.     

Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

建基岩体开挖前后的声波曲线特性及其成因分析

自然斜坡在形成演化过程中,受区域构造、河谷下切、地壳隆升以及外部营力(如风化卸荷)作用,加之岩体物理力学特性等多种地质环境因素影响,可在岸坡浅表层(由表及里)形成应力释放区、应力调整区和原始地应力稳定区;但在岸坡(建基)岩体人工开挖过程中,由于爆破扰动及岩体瞬间卸荷等影响,以上应力分区将重新波动调整。声波VP作为评价岩体质量优劣的一个重要指标,因具备简便、快速、准确、可靠等特点得到了广泛应用与发展。现就此以前期勘探平硐声波测试及开挖坝面岩体质量单孔声波检测结果为基础,讨论建基岩体开挖前后波速曲线的形态特征以及应力分区分布范围,并分析导致曲线形态的地质原因,以期为坝基开挖及后续声波监测工作等提供一定的科学依据。     

建基面岩体表层低波速带分布特征及其成因

坝基开挖后,表层岩体会产生松弛卸荷现象,引起表层岩体声波波速明显降低,在表层形成低波速带。某水电站坝基左岸表层低波速带空间分布特征分析结果表明:坝基岩体表层低波速带的空间分布呈层状,局部出现异常深度;坝基表层低波速带在空间上的分布状况与表层岩体浅表生时效变形、建基面地质构造等因素有关。     

水稻基因组MSAP指纹图谱构建及DNA甲基化修饰位点分离与鉴定

采用EcoR I和Hpa II/Msp I双酶切建立了适合于水稻基因组的甲基化敏感扩增多态性(MSAP)分析体系,在全基因组水平检测了水稻DNA甲基化修饰位点.以12对MSAP引物进行选择性扩增,共检测到甲基化修饰位点120个,"CCGG/GGCC"位点甲基化修饰比例为20.17%.对部分水稻基因组甲基化修饰位点进行回收,最终分离了55条存在甲基化位点变异的DNA序列,通过BLAST比对分析将其联配到水稻基因组序列上.分析表明,这些甲基化修饰位点主要集中于基因启动子区(47%)和第一外显子区(22%),在其侧翼序列中存在类似"CpG island" 典型序列特征的"CpG"二核苷酸成簇富集区.在此基础上,对应用MSAP技术分离水稻基因组DNA甲基化修饰位点的有效性以及水稻基因组序列中"CpG island"类似序列分布特征和生物意义进行了讨论.     

Plant Responses to Herbivory,Wounding, and Infection

Plants have various self-defense mechanisms against biotic attacks, involving both physical and chemical barriers. Physical barriers include spines, trichomes, and cuticle layers, whereas chemical barriers include secondary metabolites (SMs) and volatile organic compounds (VOCs). Complex interactions between plants and herbivores occur. Plant responses to insect herbivory begin with the perception of physical stimuli, chemical compounds (orally secreted by insects and herbivore-induced VOCs) during feeding. Plant cell membranes then generate ion fluxes that create differences in plasma membrane potential (Vm), which provokes the initiation of signal transduction, the activation of various hormones (e.g., jasmonic acid, salicylic acid, and ethylene), and the release of VOCs and SMs. This review of recent studies of plant–herbivore–infection interactions focuses on early and late plant responses, including physical barriers, signal transduction, SM production as well as epigenetic regulation, and phytohormone responses.     

Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism

Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body’s metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.