Streptomyces pratensis S10 inhibits spread of Fusarium graminearum invasive hyphae and toxisome formation in wheat plants.

Fusarium head blight (FHB) of wheat, mainly caused by Fusarium graminearum, leads to severe economic losses worldwide. Effective management measures for controlling FHB are not available, due to a lack of resistant cultivars. Currently, the utilization of biological control is a promising approach that can be used to help manage FHB. Previous studies have confirmed that Streptomyces pratensis S10 harbors excellent inhibitory effects on F. graminearum. However, there is no information regarding invasive hyphae of F. graminearum are inhibited by S10. Thus, we investigated the effects of S10 on F. graminearum strain PH-1 hyphae extension, toxisome formation, and TRI5 gene expression on wheat plants via microscopic observation. The results showed that S10 effectively inhibited spread of F. graminearum hyphae along the rachis, restricting the infection of neighboring florets via the phloem. In the presence of S10, the hyphal growth is impeded by formation of dense cell wall thickenings in the rachis internode surrounding the F. graminearum infection site, avoiding cell plasmolysis and collapse. We further demonstrated that S10 largely prevented cell-to-cell invasion of fungal hyphae inside wheat coleoptiles using a constitutively green fluorescence protein-expressing F. graminearum strain, PH-1. Importantly, S. pratensis S10 inhibited toxisome formation and TRI5 gene expression in wheat plants during infection. Collectively, these findings indicated that S. pratensis S10 prevents spread of F. graminearum invasive hyphae via the rachis.

Associations of one-carbon metabolism-related gene polymorphisms with breast cancer risk are modulated by diet, being higher when adherence to the Mediterranean dietary pattern is low.

PURPOSE: Breast cancer is more likely attributed to a combination of genetic variations and lifestyle factors. Both one-carbon metabolism and diet-related factors could interfere with the carcinogenesis of breast cancer (BC), but whether diet consumed underlie a specific metabolism pathway could influence the impact of genetic variants on breast cancer risk remains equivocal. METHODS: A case-control study of the Chinese female population (818 cases, 935 controls). 13 SNPs in eight one-carbon metabolism-related genes (MTHFD1, TYMS, MTRR, MAT2B, CDO1, FOLR1, UNG2, ADA) were performed. Diet was assessed by a validated food-frequency questionnaire. We examined the associations of the adherence to the Mediterranean dietary pattern (MDP) and single-nucleotide polymorphisms (SNPs) of one-carbon metabolism with breast cancer risk. We constructed an aggregate polygenic risk score (PRS) to test the additive effects of genetic variants and analyzed the gene-diet interactions. RESULTS: High adherence (highest quartile) to the MDP decreased the risk of breast cancer among post- but not premenopausal women, respectively (OR = 0.54, 95% CI = 0.38 to 0.78 and 0.90, 0.53 to 1.53). Neither of the polymorphisms or haplotypes was associated with breast cancer risk, irrespective of menopause. However, a high PRS (highest quartile) was associated with more than a doubling risk in both post- and premenopausal women, respectively (OR = 1.95, 95% CI = 1.32 to 2.87 and 2.09, 1.54 to 2.85). We found a gene-diet interaction with adherence to the MDP for aggregate PRS (P-interaction = 0.000) among postmenopausal women. When adherence to the MDP was low (< median), carries with high PRS (highest quartile) had higher BC risk (OR = 2.80, 95% CI = 1.55 to 5.07) than low PRS (lowest quartile), while adherence to the MDP was high (≥ median), the association disappeared (OR = 1.57, 95% CI = 0.92 to 2.66). CONCLUSION: High adherence to the MDP may counteract the genetic predisposition associated with one-carbon metabolism on breast cancer risk in postmenopausal women.

Association between dietary patterns and risk of breast cancer in Chinese female population: a latent class analysis.

OBJECTIVE: To determine if specific dietary patterns are associated with breast cancer (BC) risk in Chinese women. DESIGN: Latent class analysis (LCA) was performed to identify generic dietary patterns based on daily food-frequency data. SETTING: The Chinese Wuxi Exposure and Breast Cancer Study (2013-2014). PARTICIPANTS: A population-based case-control study (695 cases, 804 controls). RESULTS: Four dietary patterns were identified, Prudent, Chinese traditional, Western and Picky; the proportion in the controls and cases was 0·30/0·32/0·16/0·23 and 0·29/0·26/0·11/0·33, respectively. Women in Picky class were characterised by higher extreme probabilities of non-consumption of specific foods, the highest probabilities of consumption of pickled foods and the lowest probabilities of consumption of cereals, soya foods and nuts. Compared with Prudent class, Picky class was associated with a higher risk (OR = 1·42, 95 % CI 1·06, 1·90), while the relevant association was only in post- (OR = 1·44, 95 % CI 1·01, 2·05) but not in premenopausal women. The Western class characterised by high-protein, high-fat and high-sugar foods, and the Chinese traditional class characterised by typical consumption of soya foods and white meat over red meat, both of them showed no difference in BC risk compared with Prudent class did. CONCLUSIONS: LCA captures the heterogeneity of individuals embedded in the population and could be a useful approach in the study of dietary pattern and disease. Our results indicated that the Picky class might have a positive association with the risk of BC.

The synergistic effect between adult weight changes and CYP24A1 polymorphisms is associated with pre- and postmenopausal breast cancer risk.

PURPOSE: Vitamin D (VD) metabolism regulates adipose tissue, lipogenesis inflammation, and tumor growth. CYP24A1 is the key enzyme for metabolic inactivation of active VD (1,25(OH)2D3). We examined whether common germline single nucleotide polymorphisms (SNPs) in the CYP24A1 gene could affect the association between adult weight gain and breast cancer (BC) risk. METHODS: The population-based case-control study included 818 patients with primary BC and 935 residence and age matched healthy controls. We studied the relationships between CYP24A1 gene SNPs (rs2209314, rs2585428, rs2762941, rs3787555, rs4809959, rs73913757, rs912505, and rs927a650), adult weight change and BC risk. Gene-weight change interactions were analyzed. RESULTS: Neither of CYP24A1 gene SNPs was associated with BC risk in the study participants. However, we found consistent gene-weight interactions with increasing adult weight gain for CYP24A1-rs2762941 (P-interaction = 0.0089) and CYP24A1-rs927650 (P-interaction = 0.0283). Adult weight gain has a higher premenopausal BC risk with double variant T alleles of rs927650 compared to women carrying at least one wild-type C allele (OR for TT = 1.82, 95% CI 1.10-3.01; for CT = 0.93, 95% CI 0.76-1.14; for CC = 1.12 95% CI 0.93-1.35). Women with double wild-type A alleles were at a higher postmenopausal BC risk compared to those carrying at least one variant-type G allele (OR for AA = 1.51, 95% CI 1.29-1.76; for AG = 1.13, 95% CI 0.98-1.30; for GG = 1.22 95% CI 0.95-1.57). When stratified by CYP24A1 SNPs genotypes, weight gain in adulthood increased postmenopausal BC risk of women with homozygous allele compared to women with heterozygotes allele. CONCLUSION: Significant interactions of weight change with CYP24A1 polymorphisms suggest CYP24A1 as a potential link between weight change and BC risk and the possibility that the impact of adult weight gain on postmenopausal BC risk may be enhanced by homozygous alleles of CYP24A1 SNPs.

The evolutionary and transmission characteristic of HIV-1 CRF07_BC in Nanjing, Jiangsu.

To understand the epidemiology, evolutionary and transmission characteristics of HIV-1 CRF07_BC in Nanjing, China. One hundred and fifty-nine patients with HIV-1 CRF07_BC were recruited. DNA sequencing, phylogenetic analysis, and molecular transmission cluster analysis were conducted to determine the molecular epidemiology and evolutionary characteristics. Of these HIV-1-infected patients, 95.6% were male, and men who sex with men (76.7%) were the main transmission route. Only 34.0% of these cases were born in Nanjing, and most of them (64.8%) reported having multiple sex partners in the last 6 months. The maximum likelihood phylogenetic analyses of HIV-1 CRF07_BC revealed two lineages. Overall, 67.3% of Nanjing sequences were connected to at least one other individual distributed in 11 clusters, and the average degree was 21.2 with range (1-178). The clustered patients were more likely to be male. The time to a most recent common ancestor for the early HIV-1 CRF07_BC circulating in Nanjing was estimated to be 1998.71[1997.36-2001.07]. The mean estimated evolutionary rate for the epidemic cluster was slightly lower at 2.38[2.12-2.65] × 10-3 per site per year with the relaxed exponential clock model. HIV-1 CRF07_BC was transmitted into Nanjing more than 20 years ago from Yunnan and has become one of the most predominant subtypes with a higher evolutionary rate than before.

Adult weight change and the risk of pre- and postmenopausal breast cancer in the Chinese Wuxi Exposure and Breast Cancer Study.

PURPOSE: The accumulating evidence indicates that weight gain in adulthood is more predictive of breast cancer risk than absolute body weight. However, the relative impact of timing of weight gain in adulthood on breast cancer as well as other characteristics of the association between weight and breast cancer has not been well documented. METHODS: This population-based case-control study of breast cancer included 818 patients with newly diagnosed primary breast cancer and 935 residence and age-matched healthy controls. The body weight values at 18 years old, 1 year before diagnosis, and at menopause were obtained during in-person interviews. Unconditional logistic regression was used to estimate the effects of the weight change over adulthood on breast cancer risk. Linear mixed-effects regression was also applied as a secondary analysis. RESULTS: We found that the increased risk of breast cancer was associated with the weight gain in adulthood among postmenopausal women (OR 1.23; 95% CI 1.10-1.37 per 5 kg increase) but not in the premenopausal women. The risk associated with weight gain since menopause (OR 1.65; 95% CI 1.28-2.14 a 5-kg increase) was higher than that from age 18 to menopause (OR 1.14; 95% CI 1.02, 1.28 a 5-kg increase). The association tended to be stronger in those with higher waist circumference and who had never used hormone replacement therapy (HRT). Women who had never used HRT, the increased risk of breast cancer associated with weight gain was more consistent in leaner women at age 18 (BMI < 18.5) or at menopause (BMI < 24). CONCLUSIONS: Our findings indicated that weight gain has significant impact on postmenopausal breast cancer risk. The time periods of weight gain, central body fat, and HRT may affect the observed association, which should be further studied.

Molecular evolution of methylesterase family genes and the BnMES34 is a positive regulator of Plasmodiophora brassicae stress response in Arabidopsis.

Methylesterases (MES) are involved in hydrolysis of carboxylic esters, which have substantial roles in plant metabolic activities and defense mechanisms. This study aimed to comprehensively investigate Brassica napus BnMESs and characterize their role in response to Plasmodiophora brassicae stress. Forty-four BnMES members were identified and categorized into three groups based on their phylogenetic relationships and structural similarities. Through functional predictions in the promoter regions and analysis of RNA-Seq data, BnMES emerged as pivotal in growth, development, and stress responses to B. napus, particularly BnMES34, was strongly induced in response to P. brassicae infection. Gene Ontology analyses highlighted BnMES34's role in regulation of plant disease resistance responses. Furthermore, overexpression of BnMES34 in A. thaliana exhibited milder clubroot symptoms, and reduced disease indices, suggesting positive regulatory role of BnMES34 in plant's response to P. brassicae stress. Molecular docking and enzyme activity verification indicated that BnMES34 has the ability to generate salicylic acid via methyl salicylate, and further experimentally validated in vivo. This discovery indicates that the overexpression of BnMES34 in Arabidopsis confers resistance against clubroot disease. Overall, our research suggests that BnMES34 has a beneficial regulatory role in enhancing stress resistance to P. brassicae in B. napus.

Venturicidin A Is a Potential Fungicide for Controlling Fusarium Head Blight by Affecting Deoxynivalenol Biosynthesis, Toxisome Formation, and Mitochondrial Structure.

Fusarium graminearum, which causes Fusarium head blight (FHB) in cereals, is one of the most devastating fungal diseases by causing great yield losses and mycotoxin contamination. A major bioactive ingredient, venturicidin A (VentA), was isolated from Streptomyces pratensis S10 mycelial extract with an activity-guided approach. No report is available on antifungal activity of VentA against F. graminearum and effects on deoxynivalenol (DON) biosynthesis. Here, VentA showed a high antagonistic activity toward F. graminearum with an EC50 value of 3.69 µg/mL. As observed by scanning electron microscopy, after exposure to VentA, F. graminearum conidia and mycelia appeared abnormal. Different dyes staining revealed that VentA increased cell membrane permeability. In growth chamber and field trials, VentA effectively reduced disease severity of FHB. Moreover, VentA inhibited DON biosynthesis by reducing pyruvic acid, acetyl-CoA production, and accumulation of reactive oxygen species (ROS) and then inhibiting trichothecene (TRI) genes expression and toxisome formation. These results suggest that VentA is a potential fungicide for controlling FHB.

Thyroid hormone activities of neutral and anionic hydroxylated polybrominated diphenyl ethers to thyroid receptor ß: A molecular dynamics study.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as the strong endocrine disrupting chemicals to humans, which show structural similarity with endogenous thyroid hormones (THs) and thus disrupt the functioning of THs through competitive binding with TH receptors (TRs). Although previous studies have reported the hormone activities of some OH-PBDEs on TH receptor ß (TRß), the interaction mechanism remains unclear. Furthermore, hydroxyl dissociation of OH-PBDEs may alter their TR disrupting activities, which has not yet been investigated in depth. In this work, we selected 18 OH-PBDEs with neutral and anionic forms and performed molecular dynamics (MD) simulations to estimate their binding interactions with the ligand binding domain (LBD) of TRß. The results demonstrate that most of OH-PBDEs have stronger binding affinities to TRß-LBD than their anionic counterparts, and the hydroxyl dissociation of ligands differentiate the major driving force for their binding. More Br atoms in OH-PBDEs can result in stronger binding potential with TRß-LBD. Moreover, 5 hydrophobic residues, including Met313, Leu330, Ile276, Leu346, and Phe272, are identified to have important contributions to bind OH-PBDEs. These results clarify the binding mechanism of OH(O-)-PBDEs to TRß-LBD at the molecular level, which can provide a solid theoretical basis for accurate assessment of TH disrupting effects of these chemicals.

Adherence to the Vegetable-Fruit-Soy Dietary Pattern, a Reference From Mediterranean Diet, Protects Against Postmenopausal Breast Cancer Among Chinese Women.

Background: The diet-center hypothesis has gained much support from the apparent protective effect of the Mediterranean diet on breast cancer. However, the evidence of the association between Mediterranean diet adherence and breast cancer molecular subtypes remains small, especially in non-Mediterranean populations. Methods: The subjects from the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study, included 818 patients and 935 healthy controls. A validated food frequency questionnaire used for diet assessment and a modified version of the alternate Mediterranean Diet Score, which is called the alternate Chinese Diet Score, was developed to assess adherence to a migrated Chinese version of the Mediterranean diet, which we called the vegetable-fruit-soy dietary pattern. Soy foods, rapeseed oil, and coarse cereals replaced legumes, olive oil, and whole grains reflecting the cuisine of the region. We examined the association between the vegetable-fruit-soy diet adherence and breast cancer risk, stratified by menopause status (pre- or postmenopausal) and receptor status [estrogen-receptor (ER), progesterone-receptor (PR) status, and human epidermal growth factor 2 (HER2)] oncogene expression, followed by five specific combinations (ER+, ER-, ER+/PR+,ER-/PR-, and ER-/PR-/HER2-). Results: The results suggest that the vegetable-fruit-soy dietary pattern was inversely associated with postmenopausal breast cancer risk [4th vs. 1st quartile, odds ratio (OR) = 0.57, 95%CI = 0.41, 0.80; P trend < 0.001] and that the inverse association was somewhat stronger to detect among ER- subtypes (OR = 0.63; 95%CI = 0.37, 0.94; P trend = 0.003) and ER-/PR-subtypes (OR = 0.64; 95%CI = 0.41, 0.93; P trend = 0.012). We did not observe any significant association between the vegetable-fruit-soy diet characteristics and ER+ subtype, as well as between PR+ and ER+/PR+ subtypes. Conclusion: The favorable influence from the Mediterranean diet may also apply to Chinese women. The vegetable-fruit-soy dietary pattern may reduce the risk of postmenopausal breast cancer, particularly among ER- subtype, and ER-/PR-subtype.

Association Between Dietary Patterns and Plasma Lipid Biomarker and Female Breast Cancer Risk: Comparison of Latent Class Analysis (LCA) and Factor Analysis (FA).

Background: Diet research focuses on the characteristics of "dietary patterns" regardless of the statistical methods used to derive them. However, the solutions to these methods are both conceptually and statistically different. Methods: We compared factor analysis (FA) and latent class analysis (LCA) methods to identify the dietary patterns of participants in the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study that included 818 patients and 935 healthy controls. We examined the association between dietary patterns and plasma lipid markers and the breast cancer risk. Results: Factor analysis grouped correlated food items into five factors, while LCA classified the subjects into four mutually exclusive classes. For FA, we found that the Prudent-factor was associated with a lower risk of breast cancer [4th vs. 1st quartile: odds ratio (OR) for 0.70, 95% CI = 0.52, 0.95], whereas the Picky-factor was associated with a higher risk (4th vs. 1st quartile: OR for 1.35, 95% CI = 1.00, 1.81). For LCA, using the Prudent-class as the reference, the Picky-class has a positive association with the risk of breast cancer (OR for 1.42, 95% CI = 1.06, 1.90). The multivariate-adjusted model containing all of the factors was better than that containing all of the classes in predicting HDL cholesterol (p = 0.04), triacylglycerols (p = 0.03), blood glucose (p = 0.04), apolipoprotein A1 (p = 0.02), and high-sensitivity C-reactive protein (p = 0.02), but was weaker than that in predicting the breast cancer risk (p = 0.03). Conclusion: Factor analysis is useful for understanding which foods are consumed in combination and for studying the associations with biomarkers, while LCA is useful for classifying individuals into mutually exclusive subgroups and compares the disease risk between the groups.

Molecular characteristic of HIV-1 CRF01_AE in Nanjing from 2015 to 2017.

OBJECTIVE: To investigate the evolutionary dynamics and characteristic of the molecular transmission networks of HIV-1 CRF01_AE in Nanjing. METHODS: Viral samples were collected from 580 newly diagnosed HIV-1-infected patients. HIV-1 pol sequences were obtained and used for for molecular evolutionary analyses. The ML trees were constructed by MEGA 6.0 using under GTR+ G + I model with 1000 bootstrap replicates. The emergence and estimation of tMRCA and the evolutionary rate of the different CRF01_AE clusters were inferred using Bayesian phylogenetic analysis approaches implemented in the BEAST package. Pairwise genetic distances were calculated under the Tamura-Nei 93 model, a genetic distance threshold of ≤1.2% was used to identify potential transmission clusters. Network diagrams were plotted using Cytoscape 3.3.0. RESULTS: Of these HIV-1-infected patients, 551 (91.5%) were males. The largest number of infections were attributed to homosexual (462, 79.7%). A total of 518 full-length pol genes were successfully amplified, based on the phylogenetic analysis CRF01_AE was the most predominantly circulating strain (45.0%, 233/518). As shown in the ML tree, three distinct clusters were observed. The 'Nanjing lineage' 1, 2, 3 has an estimated tMRCA around1996.61, 1993.61, 1984.61 respectively. Of 233 Nanjing sequences, 123 (55.2%) distributed in 30 molecular clusters, average Links/node was 7.8 with range (1-33), most of Nanjing strains shared links with local strains. CONCLUSION: HIV-1 CRF01_AE was the most predominantly circulating strain, the epidemic of CRF01_AE in Nanjing was driven by multiple clusters of HIV-1 strains, and most CRF01_AE stains in our study were estimated to have originated in China in the 1990s.

Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis.

Fowl adenovirus serotype 4 (FAdV-4) strain SD1511 was isolated from chickens with severe inclusion body hepatitis and hydropericardium syndrome in Shandong Province, China. The isolate was cultured in primary chicken embryo kidney cells. A study of pathogenicity indicated that SD1511 readily infected 7-35-d-old chickens by intramuscular injection and intranasal and oral routes, causing 50%-100% mortality. The 35-d-old chickens suffered more severe infection than 7- and 21-d-old chickens with mortality highest in the intramuscular injection group. The serum from surviving chickens showed potent viral neutralizing capability. The complete genome of SD1511 was sequenced and analyzed. The strain was found to belong to the FAdV-4 cluster with more than 99% identity with the virulent FAdV-4 strains isolated in China in recent years except for some distinct variations, including deletions of open reading frame 27 (ORF27), ORF48, and part of ORF19. Our findings suggest that SD1511 might be used as a prototype strain for the study of pathogenesis and vaccine development.

Mutagenesis of diploid mammalian genes by gene entrapment.

The present study describes a genome-wide method for biallelic mutagenesis in mammalian cells. Novel poly(A) gene trap vectors, which contain features for direct cloning vector-cell fusion transcripts and for post-entrapment genome engineering, were used to generate a library of 979 mutant ES cells. The entrapment mutations generally disrupted gene expression and were readily transmitted through the germline, establishing the library as a resource for constructing mutant mice. Cells homozygous for most entrapment loci could be isolated by selecting for enhanced expression of an inserted neomycin-resistance gene that resulted from losses of heterozygosity (LOH). The frequencies of LOH measured at 37 sites in the genome ranged from 1.3 x 10(-5) to 1.2 x 10(-4) per cell and increased with increasing distance from the centromere, implicating mitotic recombination in the process. The ease and efficiency of obtaining homozygous mutations will (i) facilitate genetic studies of gene function in cultured cells, (ii) permit genome-wide studies of recombination events that result in LOH and mediate a type of chromosomal instability important in carcinogenesis, and (iii) provide new strategies for phenotype-driven mutagenesis screens in mammalian cells.

The high-mobility-group box protein SSRP1/T160 is essential for cell viability in day 3.5 mouse embryos.

The high-mobility-group (HMG) SSRP1 protein is a member of a conserved chromatin-remodeling complex (FACT/DUF/CP) implicated in DNA replication, basal and regulated transcription, and DNA repair. To assist in the functional analysis of SSRP1, the Ssrp1 gene was targeted in murine embryonic stem cells, and the mutation was introduced into the germ line. Embryos homozygous for the targeted allele die soon after implantation, and preimplantation blastocysts are defective for cell outgrowth and/or survival in vitro. The Ssrp1 mutation was also crossed into a p53 null background without affecting growth and/or survival defects caused by loss of Ssrp1 function. Thus, Ssrp1 appears to encode nonredundant and p53-independent functions that are essential for cell viability.

Transcriptome and Metabolome Analyses Provide Insights into the Occurrence of Peel Roughing Disorder on Satsuma Mandarin (Citrus unshiu Marc.) Fruit.

Roughing disorder (RD) is a significant quality barrier in citrus fruit, prevalent on easy-peeling mandarins. As RD is not yet well-understood, this study aimed to examine the changes and synergic molecular processes involved in peel RD. Peel with RD was induced by severely defruiting Satsuma mandarin trees. Morphology observations, RNA-sequencing, and targeted and untargeted metabolic analyses were conducted. The results showed that the primary metabolites of sugars, organic acids and amino acids are dramatically changed in RD peel. The RD peel was always characterized by higher magnesium content during development. Comparative transcriptome profiling was performed for CK and RD peels at 30, 80, and 170 days after full bloom (DAFB) which represented fruit at cell division stage, cell enlargement stage and fruit maturity stage, respectively. Physiological and molecular biological evidence suggested that the month after full bloom is a crucial stage for RD initiation. A total of 4,855 differentially expressed genes (DEGs) in RD peel, relative to CK peel were detected at cell division stage, about 2 to 4-fold more than other stages had. Among the differentially expressed transcription factors, the bHLH family were affected most by RD, and six bHLH transcription factors functionally involved in GA metabolism were assessed to associate with RD occurrence. Gene set enrichment analysis suggested that RD significantly altered starch and GA metabolism in peel. Higher starch content and hydrolysed chain status were found in RD peel at cell division stage. RD occurrence on the peel was influenced significantly by GA, especially abundant GA before July. These changes may mean a significant alteration in sink strength of RD peel. The findings of this study provide insights into the emergence, development and molecular mechanisms of RD.

Vitamin D receptor genetic polymorphisms and tuberculosis among Chinese Han ethnic group.

BACKGROUND: In epidemiological studies, tuberculosis (TB) appears intimately with vitamin D insufficiency whereas its relationship with vitamin D receptor (VDR) polymorphism caused by radical difference remains unspecified. This study aimed to investigate the relationship between vitamin D genetic polymorphism and tuberculosis in Han ethnic group. METHODS: Meta-analysis was adopted in the synthetic quantitative analysis of documents home and abroad on the relationship between vitamin D genetic polymorphisms and tuberculosis, which were openly published during June 2000 to January 2010. Random effect model and fixed effect model analyses were used to calculate the incorporated odds ratio (OR) based on the heterogeneity test data. RESULTS: A total of 6 eligible studies were included in this analysis. The FokI-ff genotype showed a significant marginal association (Fixed effect model: OR 1.91, 95%CI 1.44-2.52; Random effect model: OR 1.91, 95%CI 0.94-3.88), yet TaqI polymorphisms was not significantly related to TB. CONCLUSION: The interaction between FoKI genotype polymorphism and TB observed demonstrates that vitamin D deficiency might exist as a risk factor during the development of TB in Han ethnic group and more evidences needed to validate the conclusion.

Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function.

Prefoldin is a hexameric chaperone that facilitates posttranslational folding of actins and other cytoskeletal proteins by the Tcp1-containing ring complex chaperonin, TriC. The present study characterized mice with a null mutation in Pfdn1, which encodes the first subunit of the Prefoldin complex. Pfdn1-deficient mice displayed phenotypes characteristic of defects in cytoskeletal function, including manifestations of ciliary dyskinesia, neuronal loss, and defects in B and T cell development and function. B and T cell maturation was markedly impaired at relatively early stages, namely at the transitions from pre-pro-B to pre-B cells in the bone marrow and from CD4-CD8- double-negative to CD4+CD8+ double-positive T cells in the thymus. In addition, mature B and T lymphocytes displayed cell activation defects upon Ag receptor cross-linking accompanied by impaired Ag receptor capping in B cells. These phenotypes illustrate the importance of cytoskeletal function in immune cell development and activation.

Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability.

Widespread losses of heterozygosity (LOH) in human cancer have been thought to result from chromosomal instability caused by mutations affecting DNA repair/genome maintenance. However, the origin of LOH in most tumors is unknown. The present study examined the ability of carcinogenic agents to induce LOH at 53 sites throughout the genome of normal diploid mouse ES cells. Brief exposures to nontoxic levels of methylnitrosourea, diepoxybutane, mitomycin C, hydroxyurea, doxorubicin, and UV light stimulated LOH at all loci at frequencies ranging from 1-8 x 10(-3) per cell (10-123 times higher than in untreated cells). This greatly exceeds the frequencies at which these agents have been reported to induce point mutations and is comparable to the rates of LOH observed in ES cells lacking the gene responsible for Bloom syndrome, an inherited DNA repair defect that results in greatly increased risk of cancer. These results suggest that LOH contributes significantly to the carcinogenicity of a variety of mutagens and raises the possibility that genome-wide LOH observed in some human cancers may reflect prior exposure to genotoxic agents rather than a state of chromosomal instability during the carcinogenic process. Finally, as a practical matter, chemically induced LOH is expected to enhance the recovery of homozygous recessive mutants from phenotype-based genetic screens in mammalian cells.