MAPK regulates cell cycle progression in pig oocytes and fertilized eggs

Oocytes collected from prepubertal gilt ovaries were matured in vitro (IVM), and fertilized in vitro (IVF) or electrically activated. Phosphorylation of mitogenactivated protein kinase (MAPK) was detected with SDS-PAGE and Western blotting, and translocation of ERK₂ was observed with immunofluorescent cytochemistry. We found that the quantity of MAPK kept unchanged during oocyte maturation. There was no phosphorylated MAPK in porcine oocytes at the germinal vesicle (GV) stage; a little MAPK was phosphorylated at 20 h of IVM; a high level phosphorylation was detected at 30 h, while MAPK phosphorylation decreased at 36 h; and then MAPK phosphorylation increased again to the peak level from 40 to 60 h. ERK2 translocated from the peripheral cytoplasm to inner cytoplasm and nuclear area during oocyte maturation. There was nearly no phosphorylated MAPK at 18 and 20 h of electrically activated oocytes, but phosphorylation increased at 22 h. There was no phosphorylated MAPK at 12 h of IVF, while phosphorylation resumed at 16 h. These results suggest that MAPK may play an important regulatory role in MI-MII transition, pronucleus formation and the initiation of the first mitosis in pig eggs.     

Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity

A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes.     

肠道菌群在肥胖及相关的代谢性疾病发生发展中的地位和作用

肥胖及相关的代谢性疾病近年来已经成为威胁全球的公共健康问题。越来越多的证据表明,与人类共生的肠道菌群不仅在消化、免疫和抗病方面有不可替代的作用,而且与非传染性的代谢失调相关,特别是其可以通过调节宿主脂肪吸收存储相关的基因,影响后者的能量平衡。因此,肠道菌群可能是在膳食结构变化与人的遗传体质的相互作用下导致肥胖等代谢性疾病发生的一个重要环节。对该环节的深入研究,可能带来代谢性疾病预防和控制策略的革命性的变化。     

肥胖易感及肥胖抵抗动物模型的建立与评价

建立肥胖易感(OP)和肥胖抵抗(OR)大鼠模型并进行评价。以高脂饲料喂饲雄性SD大鼠3周。根据体重筛选出OP和OR大鼠。继续喂饲高脂饲料10周,期间检测大鼠体重、体长,计算Lee’s指数、BMI指数。实验结束处死动物,测量体脂肪含量。OP组动物与对照组相比,体重、Lee’s指数、BMI指数、体脂含量等指标均具有显著性差异。OR组动物的各项指标与对照组动物相近,提示用高脂饮食诱导肥胖与肥胖抵抗的动物模型造模成功。     

Abdominal obesity and metabolic syndrome

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.     

肥胖的机制与科学减肥

肥胖问题是严重影响人类生活的现代疾病.其病因极为复杂,涉及遗传、生理、生活方式等多种因素.肥胖可以导致众多的并发病症.控制肥胖的手段有多种选择,运动与合理的饮食是最安全、可行的方法.合理的运动可以有效地控制、调整身体成分,达到健康减肥的目的.综述了肥胖的机制及科学减肥的方法.     

含硫废水的处理与研究进展

介绍了目前国内外对工业含硫废水的常规处理方法以及应用研究情况,对新兴的超临界水氧化法和应用越来越广泛的生物处理法在含硫废水处理的实验研究中所取得的成果,以及工程应用中需解决的问题进行了分析.指出各种物理化学处理方法及生化处理方法的特点和局限性,并探讨了一些新兴含硫废水处理方法的发展前景.     

一个Dirichlet级数的解析性质

在此给出了一个Dirichlet级数,研究了其渐近公式及Res=2附近的阶的估计等若干性质.     

Stromal fibroblasts in cancer initiation and progression

It is widely accepted that the development of carcinoma--the most common form of human cancer--is due to the accumulation of somatic mutations in epithelial cells. The behaviour of carcinomas is also influenced by the tumour microenvironment, which includes extracellular matrix, blood vasculature, inflammatory cells and fibroblasts. Recent studies reveal that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated. These new findings have important therapeutic implications.     

Target size regulates calibre and myelination of sympathetic axons

Axons in vertebrate peripheral nerves are ensheathed by Schwann cells. For some axons, this sheath consists of a single layer of glial cell cytoplasm and plasma membranes; for other axons, Schwann cells form multilayered myelin. Whether or not a Schwann cell makes myelin is determined by a signal from the axon, but the nature of this signal is not known. Here I show that sympathetic postganglionic axons, which are normally not myelinated, become myelinated when their calibre is increased as a result of increasing the size of the peripheral target they innervate. This result implies that axon calibre, which is known to be correlated with myelination, is in fact the crucial determinant of whether an axon becomes myelinated. Furthermore, the finding that increasing or decreasing target size causes corresponding increases or decreases in axon size indicates that axon calibre is itself regulated by retrograde signals from peripheral target tissues.     

主位推进：理论背景以及存在问题

主位推进理论被广泛地用于分析语篇，然而真正有说服力有影响力的应用研究并不多见，究其原因，主要在于大的理论框架下有些具体操作层面的问题尚待统一。这些问题有的较好解决，有的由于主住推进本身的复杂性和主观性，难以根本解决，从而影响了进一步应用研究的信度。     

Linear ubiquitination prevents inflammation and regulates immune signalling

Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKγ or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1β was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.     

生命早期1000天的营养与肥胖

 生命早期1000天的营养暴露与儿童期乃至成年后肥胖及慢性疾病的发生风险关系密切。本文将生命早期1000天划分为3个营养阶段,即宫内营养期、母乳或婴儿配方食品期、辅食添加及早期饮食期,并对各阶段中可能暴露的多种营养相关危险因素进行了系统综述。其中,宫内营养期可能存在的主要危险因素是,母亲孕前体质指数过高、妊娠期体重增加量过高、孕期患有糖尿病、携带代谢性疾病易感基因;母乳或婴儿配方食品期可能存在的主要危险因素是,由于食用配方食品导致的婴儿生长速度过快、能量和蛋白质摄入过高、多不饱和脂肪酸摄入过低;而在辅食添加阶段可能存在的主要危险因素是,婴儿体重增加过快、固态食物添加过早、蛋白质摄入过高、肠道微生物。