Mutant residues suppressing rho(0)-lethality in Kluyveromyces lactis occur at contact sites between subunits of F(1)-ATPase

Characterisation of 35 Kluyveromyces lactis strains lacking mitochondrial DNA has shown that mutations suppressing rho(0)-lethality are limited to the ATP1, 2 and 3 genes coding for the alpha-, beta- and gamma- subunits of mitochondrial F(1)-ATPase. All atp mutations reduce growth on glucose and three alleles, atp1-2, 1-3 and atp3-1, produce a respiratory deficient phenotype that indicates a drop in efficiency of the F(1)F(0)-ATP synthase complex. ATPase activity is needed for suppression as a double mutant containing an atp allele, together with a mutation abolishing catalytic activity, does not suppress rho(0)-lethality. Positioning of the seven amino acids subject to mutation on the bovine F(1)-ATPase structure shows that two residues are found in a membrane proximal region while five amino acids occur at a region suggested to be a molecular bearing. The intriguing juxtaposition of mutable amino acids to other residues subject to change suggests that mutations affect subunit interactions and alter the properties of F(1) in a manner yet to be determined. An explanation for suppressor activity of atp mutations is discussed in the context of a possible role for F(1)-ATPase in the maintenance of mitochondrial inner membrane potential.     

Occupational Electromagnetic Field Exposures Associated with Sleep Quality: A Cross-Sectional Study

Background

Exposure to electromagnetic field (EMF) emitted by mobile phone and other machineries concerns half the world’s population and raises the problem of their impact on human health. The present study aims to explore the effects of electromagnetic field exposures on sleep quality and sleep duration among workers from electric power plant.

Methods

A cross-sectional study was conducted in an electric power plant of Zhejiang Province, China. A total of 854 participants were included in the final analysis. The detailed information of participants was obtained by trained investigators using a structured questionnaire, which including socio-demographic characteristics, lifestyle variables, sleep variables and electromagnetic exposures. Physical examination and venous blood collection were also carried out for every study subject.

Results

After grouping daily occupational electromagnetic exposure into three categories, subjects with long daily exposure time had a significantly higher risk of poor sleep quality in comparison to those with short daily exposure time. The adjusted odds ratios were 1.68 (95%CI: 1.18, 2.39) and 1.57 (95%CI: 1.10, 2.24) across tertiles. Additionally, among the subjects with long-term occupational exposure, the longer daily occupational exposure time apparently increased the risk of poor sleep quality (OR (95%CI): 2.12 (1.23∼3.66) in the second tertile; 1.83 (1.07∼3.15) in the third tertile). There was no significant association of long-term occupational exposure duration, monthly electric fee or years of mobile-phone use with sleep quality or sleep duration.

Conclusions

The findings showed that daily occupational EMF exposure was positively associated with poor sleep quality. It implies EMF exposure may damage human sleep quality rather than sleep duration.     

Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

In regenerative tissues, one of the strategies to protect stem cells from genetic aberrations, potentially caused by frequent cell division, is to transiently expand the stem cell daughters before further differentiation. However, failure to exit the transit amplification may lead to overgrowth, and the molecular mechanism governing this regulation remains vague. In a Drosophila mutagenesis screen for factors involved in the regulation of germline stem cell (GSC) lineage, we isolated a mutation in the gene CG32364, which encodes a putative RNA-binding protein (RBP) and is designated as tumorous testis (tut). In tut mutant, spermatogonia fail to differentiate and over-amplify, a phenotype similar to that in mei-P26 mutant. Mei-P26 is a TRIM-NHL tumor suppressor homolog required for the differentiation of GSC lineage. We found that Tut binds preferentially a long isoform of mei-P26 3′UTR, and is essential for the translational repression of mei-P26 reporter. Bam and Bgcn are both RBPs that have also been shown to repress mei-P26 expression. Our genetic analyses indicate that tut, bam, or bgcn is required to repress mei-P26 and to promote the differentiation of GSCs. Biochemically, we demonstrate that Tut, Bam, and Bgcn can form a physical complex in which Bam holds Tut on its N-terminus and Bgcn on its C-terminus. Our in vivo and in vitro evidence illustrate that Tut acts with Bam, Bgcn to accurately coordinate proliferation and differentiation in Drosophila germline stem cell lineage.     

Structure and Specificity of the Bacterial Cysteine Methyltransferase Effector NleE Suggests a Novel Substrate in Human DNA Repair Pathway

Enteropathogenic E. coli (EPEC) and related enterobacteria rely on a type III secretion system (T3SS) effector NleE to block host NF-κB signaling. NleE is a first in class, novel S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates a zinc-coordinating cysteine in the Npl4-like Zinc Finger (NZF) domains in TAB2/3 adaptors in the NF-κB pathway, but its mechanism of action and other human substrates are unknown. Here we solve crystal structure of NleE-SAM complex, which reveals a methyltransferase fold different from those of known ones. The SAM, cradled snugly at the bottom of a deep and narrow cavity, adopts a unique conformation ready for nucleophilic attack by the methyl acceptor. The substrate NZF domain can be well docked into the cavity, and molecular dynamic simulation indicates that Cys673 in TAB2-NZF is spatially and energetically favorable for attacking the SAM. We further identify a new NleE substrate, ZRANB3, that functions in PCNA binding and remodeling of stalled replication forks at the DNA damage sites. Specific inactivation of the NZF domain in ZRANB3 by NleE offers a unique opportunity to suggest that ZRANB3-NZF domain functions in DNA repair processes other than ZRANB3 recruitment to DNA damage sites. Our analyses suggest a novel and unexpected link between EPEC infection, virulence proteins and genome integrity.     

Prevalence of Hypertension in Rural Areas of China: A Meta-Analysis of Published Studies

Background

Hypertension is one of the leading causes of disease burden across the world. In China, the latest nationwide survey of prevalence of hypertension was ten year ago, and data in rural areas is little known. More information about hypertension prevalence could help to improve overall antihypertensive health care. We aimed to estimate the pooled prevalence of hypertension in rural areas of China.

Methods

Comprehensive electronic searches of PubMed, Web of Knowledge, Chinese Web of Knowledge, Wangfang, Weipu and SinoMed databases were conducted to identify any study in each database published from January 1, 2004 to December 31, 2013, reporting the prevalence of hypertension in Chinese rural areas. Prevalence estimates were stratified by age, area, sex, publication year, and sample size. All statistical calculations were made using the Stata Version 11.0 (College Station, Texas) and Statsdirect Version 2.7.9.

Results

We identified 124 studies with a total population of 3,735,534 in the present meta-analysis. Among people aged 18 years old in Chinese rural areas, the summarized prevalence is 22.81% (19.41%–26.41%). Subgroup analysis shows the following results: for male 24.46% (21.19%–27.89%, for female 22.17% (18.25%–26.35%). For 2004–2006: 18.94% (14.41%–23.94%), for 2007–2009, 21.24% (15.98%–27.01%) for 2010–2013: 26.68%, (20.79%–33.02%). For Northern region 25.76% (22.36%–29.32%), for Southern region 19.30%, (15.48%–24.08%).

Conclusions

The last decade witnessed the growth in prevalence of hypertension in rural areas of China compared with the fourth national investigation, which has climbed the same level as the urban area. Guidelines for screening and treatment of hypertension in rural areas need to be given enough attention.     

Analysis of DYS19 and DYS287 polymorphisms in the Han population and three other ethnic groups of northeast China

The allelic distribution of the Y-chromosome specific microsatellite DYS19 in the Han population and in the Daur, Oroqen and Ewenki ethnic groups (Northeast China) was analyzed by PCR and denatured polyacrylamide gel electrophoresis. The allelic distribution in the Han population group is as follows: A = 2.90%, B = 26.09%, C = 26.09%, D = 29.98%, E = 15.94%. This allelic distribution differs statistically significant from that observed in the three other ethnic groups (p < 0.05). Furthermore the polymorphism of the Y-chromosome specific Alu insert sequence DYS287 was tested in these four groups. However, no Alu sequence insert was found.     

rSJYB1 inhibits collagen type I protein expression in hepatic stellate cells via down‐regulating activity of collagen α1 (I) promoter

YB1 is a negative regulator in liver fibrosis. We wondered whether SJYB1, a homologous protein of YB1 from Schistosoma japonicum, has an effect on liver fibrosis in vitro. Recombinant SJYB1 (rSJYB1) protein was expressed in a bacterial system and purified by Ni‐NTA His·Bind Resin. A human hepatic stellate cell line, the LX‐2 cell line, was cultured and treated with rSJYB1. The role of rSJYB1 on LX‐2 cells was then analysed by Western blot and luciferase assay. We succeeded in expressing and purifying SJYB1 in a bacterial system and the purified rSJYB1 could be recognized by S japonicum‐infected rabbit sera. Western bolt analysis showed that rSJYB1 inhibited the expression of collagen type I, but had little effect on α‐smooth muscle actin (α‐SMA). Further analysis revealed that rSJYB1 inhibited the activity of collagen α1 (I) (COL1A1) promoter and functioned at ?1592/?1176 region of COL1A1 promoter. Our data demonstrate that rSJYB1‐mediated anti‐fibrotic activity involves inhibiting the activity of COL1A1 promoter and subsequently suppressing the expression of collagen type I in hepatic stellate cells.