Antibiotic treatment leads to the elimination of Wolbachia endosymbionts and sterility in the diplodiploid collembolan Folsomia candida

<p>Abstract</p> <p>Background</p> <p><it>Wolbachia </it>is an extremely widespread bacterial endosymbiont of arthropods and nematodes that causes a variety of reproductive peculiarities. Parthenogenesis is one such peculiarity but it has been hypothesised that this phenomenon may be functionally restricted to organisms that employ haplodiploid sex determination. Using two antibiotics, tetracycline and rifampicin, we attempted to eliminate <it>Wolbachia </it>from the diplodiploid host <it>Folsomia candida</it>, a species of springtail which is a widely used study organism.</p> <p>Results</p> <p>Molecular assays confirmed that elimination of <it>Wolbachia </it>was successfully achieved through continuous exposure of populations (over two generations and several weeks) to rifampicin administered as 2.7% dry weight of their yeast food source. The consequence of this elimination was total sterility of all individuals, despite the continuation of normal egg production.</p> <p>Conclusion</p> <p>Microbial endosymbionts play an obligatory role in the reproduction of their diplodiploid host, most likely one in which the parthenogenetic process is facilitated by <it>Wolbachia</it>. A hitherto unknown level of host-parasite interdependence is thus recorded.</p

Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Clinical outcome of patients with high-grade ccRCC (clear cell renal cell carcinoma) remains still poor despite recent advances in treatment strategies. Molecular mechanism of pathogenesis in developing high-grade ccRCC must be clarified. In the present study, we found that SAV1 was significantly downregulated with copy number loss in high-grade ccRCCs. Therefore, we investigated the SAV1 function on cell proliferation and apoptosis in vitro. Furthermore, we attempted to clarify the downstream signaling which is regulated by SAV1.</p> <p>Methods</p> <p>We performed array CGH and gene expression analysis of 8 RCC cell lines (786-O, 769-P, KMRC-1, KMRC-2, KMRC-3, KMRC-20, TUHR4TKB, and Caki-2), and expression level of mRNA was confirmed by quantitative RT-PCR (qRT-PCR) analysis. We next re-expressed SAV1 in 786-O cells, and analyzed its colony-forming activity. Then, we transfected siRNAs of SAV1 into the kidney epithelial cell line HK2 and renal proximal tubule epithelial cells (RPTECs), and analyzed their proliferation and apoptosis. Furthermore, the activity of YAP1, which is a downstream molecule of SAV1, was evaluated by western blot analysis, reporter assay and immunohistochemical analysis.</p> <p>Results</p> <p>We found that SAV1, a component of the Hippo pathway, is frequently downregulated in high-grade ccRCC. SAV1 is located on chromosome 14q22.1, where copy number loss had been observed in 7 of 12 high-grade ccRCCs in our previous study, suggesting that gene copy number loss is responsible for the downregulation of SAV1. Colony-forming activity by 786-O cells, which show homozygous loss of SAV1, was significantly reduced when SAV1 was re-introduced exogenously. Knockdown of SAV1 promoted proliferation of HK2 and RPTEC. Although the phosphorylation level of YAP1 was low in 786-O cells, it was elevated in SAV1-transduced 786-O cells. Furthermore, the transcriptional activity of the YAP1 and TEAD3 complex was inhibited in SAV1-transduced 786-O cells. Immunohistochemistry frequently demonstrated nuclear localization of YAP1 in ccRCC cases with SAV1 downregulation, and it was preferentially detected in high-grade ccRCC.</p> <p>Conclusions</p> <p>Taken together, downregulation of SAV1 and the consequent YAP1 activation are involved in the pathogenesis of high-grade ccRCC. It is an attractive hypothesis that Hippo signaling could be candidates for new therapeutic target.</p

Enzymatic Digestion of Single DNA Molecules Anchored on Nanogold-Modified Surfaces

To study enzyme–DNA interactions at single molecular level, both the attachment points and the immediate surroundings of surfaces must be carefully considered such that they do not compromise the structural information and biological properties of the sample under investigation. The present work demonstrates the feasibility of enzymatic digestion of single DNA molecules attached to nanoparticle-modified surfaces. With Nanogold linking DNA to the mica surface by electrostatic interactions, advantageous conditions with fewer effects on the length and topography of DNA are obtained, and an appropriate environment for the activities of DNA is created. We demonstrate that by using Dip-Pen Nanolithography, individual DNA molecules attached to modified mica surfaces can be efficiently digested by DNase I

Sense of coherence as a predictor of onset of depression among Japanese workers: a cohort study

<p>Abstract</p> <p>Background</p> <p>The ability to predict future onset of depression is required for primary prevention of depression. Many cross-sectional studies have reported a correlation between sense of coherence (SOC) and the presence of depressive symptoms. However, it is unclear whether SOC can predict future onset of depression. Therefore, whether measures to prevent onset of depression are needed in for persons with low SOC is uncertain. Thus, the aim of this cohort study was to determine whether SOC could predict onset of depression and to assess the need for measures to prevent onset of depression for persons with low SOC.</p> <p>Methods</p> <p>A total of 1854 Japanese workers aged 20-70 years in 2005 who completed a sense of coherence (SOC) questionnaire were followed-up until August 2007 using their sick-pay records with medical certificates. Depression was defined as a description of "depression" or "depressive" as a reason for sick leave on the medical certificates. The day of incidence of depression was defined as the first day of the sick leave. Risk ratios of SOC for onset of depression were calculated using a multivariate Cox proportional hazards model.</p> <p>Results</p> <p>Of the 1854 participants, 14 developed depression during a mean of 1.8 years of follow-up. After adjustment for gender and age, the risk ratio of high SOC compared with low SOC for sick leave from depression was 0.18 (95% confidence interval [CI], 0.04 to 0.79). The area under the receiver operating characteristic curve of SOC was 0.70 (95% CI, 0.58 to 0.82).</p> <p>Conclusions</p> <p>The SOC may be able to predict onset of depression in Japanese workers. Measures to prevent onset of depression for persons with low SOC might be required in Japanese workplaces. Thus, SOC could be useful for identifying persons at high risk for future depression.</p

The influence of methylphenidate on the power spectrum of ADHD children – an MEG study

BACKGROUND: The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG). METHODS: 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (± 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES™ 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5–3.5 Hz), Theta (T, 3.5–7.5 Hz), Alpha (A, 7.5–12.5 Hz), Beta (B, 12.5–25 Hz) and Global (GL, 1.5–25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. RESULTS: The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. CONCLUSION: Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

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The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

INTRODUCTION: Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006-2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms. METHODS: We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease. RESULTS: We identified 33 SUD, a 73% decline from 2002-2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata-exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test). DISCUSSION: Epidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ratio 01 (P = 1.36 x 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ratio 01 (P = 5.22 x 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ratio 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 x 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.published_or_final_versio