Post-translational modifications in MeHg-induced neurotoxicity

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.     

十溴联苯醚降解菌群的降解特性与组成分析

[目的]针对水体沉积物中日益严重的多溴联苯醚污染问题,以电子垃圾污染河床沉积物为种源富集驯化获得的菌群Cf3,研究该菌群对十溴联苯醚的降解特性以及其菌群结构组成.[方法]通过GC-MS分析十溴联苯醚降解后低溴代产物组成,并测定其降解率;通过DGGE技术分析了该BDE-209降解菌群的结构组成.[结果]菌群Cf3具有较强降解BDE-209的能力,经过120 d的培养,初始量为2.6 μmol的BDE-209降解率达到80.03％,OD600从0.01增长到0.21,pH由初始的6.93增加到反应结束时的8.50.菌群Cf3经过单菌落分离,共获得10株可培养细菌,通过16S rRNA基因序列比对发现,其中6株与柠檬酸杆菌属(Citrobacter spp.)具有较高同源性,其余4株与产碱杆菌属(Alcaligenes spp.)较相似.进一步采用DGGE分析菌群Cf3的结构组成时发现,除了分离得到的2个菌属外,该菌群中还含有拟杆菌属(Wolinella spp.)、氨基酸球菌属(Acidaminococcus spp.),以及随着降解时间延长而消失的脱硫弧菌属(Desulfovibrio spp.)和醋杆菌属(Acetobacterium spp.).[结论]获得了具有较强多溴联苯醚降解能力的菌群,并分析了其降解特性和群落组成,为进一步开展溴代阻燃剂等持久性有机污染物的生物修复提供宝贵的菌种资源和科学数据.     

Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity

Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA.     

CD1a、CD209 及MHCII在新生儿指皮组织中的表达及意义

目的:探讨新生儿指尖皮肤及皮下组织中树突状细胞的形态、数量和分布情况。方法:5例尸检新生儿无名指指皮组织样本,行免疫组织化学染色(CD1a、CD209和MHCⅡ标记),光镜观察。结果:新生儿指皮组织中,阳性细胞呈棕褐色,大小不等、形态多样,有数量不等的突起,呈散在或灶带状分布。CD1a标记的细胞阳性率为(23±11.9)%,多位于表皮乳头周围,血管外膜以及真皮疏松结缔组织中;CD209标记的细胞阳性率为(30±7.7)%,多位于真皮层内,血管神经分叉处,血管外膜,环层小体被囊结缔组织中;MHCⅡ的标记的细胞阳性率(8±1.9)%,多位于血管外膜及周围疏松结缔组织中。结论:稳态下,新生儿皮肤组织中存在多种分化发育程度不同的DCs(且以不成熟DCs为主),是皮肤免疫微环境的重要组成部分。     

Red porgy (Pagrus pagrus) larval feeding performance and behavior at the onset of exogenous feeding

The feeding performance and behavior at the onset of exogenous feeding, 3 to 4 days after hatching (DAH), were studied in red porgy Pagrus pagrus larvae. Similar feeding efficiency and intensity were achieved for two feeding treatments (live or freeze-dried rotifers) suggesting that prey movement is not decisive for their detection and capture and demonstrating that at first feeding red porgy larvae can ingest inert food. Larvae feeding performance was not affected by a diet shift between treatments. Based on maximum rotifers consumption and gut evacuation time at 18 °C, the daily ration was estimated as 14.035 μg, considering 14 h of feeding and a 25% egg:female rotifer ratio. Larval swimming activity measured by video recording showed a close association with gut fullness and similar swimming patterns for 3 and 4 DAH larvae. However, 20.3% larger mouth gape and 54.6% higher swimming speed of the older larvae should provide a better feeding performance and more energy needed for growth.     

The formation and stability of DC-SIGN microdomains require its extracellular moiety

Dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin (DC-SIGN) is a Ca(2+) -dependent transmembrane lectin that binds a large variety of pathogens and facilitates their uptake for subsequent antigen presentation. This receptor is present in cell surface microdomains, but factors involved in microdomain formation and their exceptional stability are not clear. To determine which domain/motif of DC-SIGN facilitates its presence in microdomains, we studied mutations at key locations including truncation of the cytoplasmic tail, and ectodomain mutations that resulted in the removal of the N-linked glycosylation site, the tandem repeats and the carbohydrate recognition domain (CRD), as well as modification of the calcium sites in the CRD required for carbohydrate binding. Confocal imaging and fluorescence recovery after photobleaching measurements showed that the cytoplasmic domain and the N-linked glycosylation site do not affect the ability of DC-SIGN to form stable microdomains. However, truncation of the CRD results in complete loss of visible microdomains and subsequent lateral diffusion of the mutants. Apart from cell adhesions, membrane domains are thought to be localized primarily via the cytoskeleton. By contrast, we propose that interactions between the CRD of DC-SIGN and the extracellular matrix and/or cis interactions with transmembrane scaffolding protein(s) play an essential role in organizing these microdomains.     

Isolation and structural characterization of new piperidine alkaloids from Prosopis affinis

The isolation of three new N-methylated piperidine-3-ol alkaloids from the bark of Prosopis affinis Spreng. (Ñandubay) is described. Together with MS and IR data, results from 1D and 2D NMR experiments allowed for the identification of N‑methyl-2-isocassine, N‑methyl-6-isocassine, and N‑methyl-6-isocarnavaline. Inspection of 1D-NOESY spectra and coupling constant data revealed that the heterocyclic moiety of the alkaloids is in fast conformational equilibrium in solution, and this behavior had to be taken into account in order to determine the relative configuration of the chiral centers of the piperidine rings.     

水稻花培品种单209抗病性的遗传学分析

单209是1977年由组合(IR26×农虎_6~2),经花药培养育成的粳稻品种。遗传学研究表明,该品种对稻瘟病和水稻白叶枯病的抗性受不同的单基因控制,而它们是由非轮回亲本IR26导入的。鉴于已发现的具白叶桔病抗性基因X(?)的材料均属籼稻。因此,单209可能是具该抗性基因的第1个粳稻品种。它已作为抗性亲本广泛应用于育种中。     

Germline genomic instability in PCNA mutants of Drosophila: DNA fingerprinting and microsatellite analysis

PCNA participates in multiple processes of DNA metabolism with an essential role in DNA replication and intervening in DNA repair. Temperature-sensitive PCNA mutants of Drosophila (mus209) are sensitive to mutagens, impair developmental processes and suppress positional-effect variegation. To investigate the role of proliferating cell nuclear antigen (PCNA) in germline genomic stability, independent mus209-defective and mus209-normal lines were established and maintained over six generations. A time course study was carried out and general genomic alterations were analyzed in the progeny by using arbitrarily primed PCR (AP-PCR) and microsatellite analysis. The AP-PCR analysis has shown that a dysfunctional PCNA leads to germline genomic instability, being the amount of genomic alterations transmitted to the progeny directly related to the number of mus209^B1 mutant alleles. In addition, we have found that the frequency of genomic alterations tends to increase over successive generations. Surprisingly, the highest microsatellite instability was found in the heterozygous mus209-defective lines, suggesting a greater mutation rate in these individuals, in comparison with the homozygous mus209-defective lines. In conclusion, our results clearly indicate that PCNA is an important factor to maintain genomic stability in germinal cells, both in the overall genome and in simple repeated sequences. The implication of PCNA mutations in transgenerational genomic instability and related to cancer susceptibility is also discussed.