Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population

BACKGROUND: Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 µg/L in the northeastern, western, and north central regions of the United States. OBJECTIVES: We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. METHODS: We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) as part of a case–control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. RESULTS: The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. CONCLUSIONS: These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases. KEY WORDS: arsenic, drinking water, immune response, lymphocytes, microarray, U.S. population. Environ Health Perspect 116:524–531 (2008). doi:10.1289/ehp.10861 available vi

ICTV Virus Taxonomy Profile: Rhabdoviridae.

This is the final version of the article. Available from the publisher via the DOI in this record.The family Rhabdoviridae comprises viruses with negative-sense (-) single-stranded RNA genomes of 10.8-16.1 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants and animals including mammals, birds, reptiles and fish, as well as arthropods which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish and agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Rhabdoviridae, which is available at www.ictv.global/report/rhabdoviridae.Production of this summary, the online chapter, and associated resources was funded by a grant from the Wellcome Trust (WT108418AIA)

Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences

Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua

Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 ± 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 ± 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an

A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The relationship between <it>Helicobacter pylori </it>infection and pancreatic cancer has been investigated in three previous studies with contradictory results. The aim of the present study was to investigate the association between <it>H. pylori </it>seropositivity and the risk for pancreatic cancer in a nested case-control study within a population based cohort.</p> <p>Methods</p> <p>Selected birth-year cohorts (born 1921–1949) of residents in Malmö, Sweden, were invited to a health screening investigation. A total of 33 346 subjects participated. Cases with pancreatic cancer (n = 87) were matched to controls (n = 263) using age, sex and time for baseline investigation as matching variables. <it>H. pylori </it>serology was analysed in stored serum samples using an enzyme-linked immunosorbent assay. Odds ratios (OR) for pancreatic cancer were calculated with 95% confidence intervals (CI) using logistic regression.</p> <p>Results</p> <p><it>H. pylori </it>seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75–2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06–13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97–4.69) adjusted for smoking).</p> <p>Conclusion</p> <p>We conclude that no association between <it>H. pylori </it>infection and the risk for pancreatic cancer was found in the total cohort. However, in never smokers and in subjects with low risk alcohol consumption, a positive <it>H. pylori </it>serology was associated with an increased risk for pancreatic cancer. These findings should be interpreted cautiously due to the limited number of cases in these subgroups.</p

Connective Tissue Growth Factor Overexpression in Cardiomyocytes Promotes Cardiac Hypertrophy and Protection against Pressure Overload

Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls

Social Status Affects the Degree of Sex Difference in the Songbird Brain

It is thought that neural sex differences are functionally related to sex differences in the behaviour of vertebrates. A prominent example is the song control system of songbirds. Inter-specific comparisons have led to the hypothesis that sex differences in song nuclei size correlate with sex differences in song behaviour. However, only few species with similar song behaviour in both sexes have been investigated and not all data fit the hypothesis. We investigated the proposed structure – function relationship in a cooperatively breeding and duetting songbird, the white-browed sparrow weaver (Plocepasser mahali). This species lives in groups of 2–10 individuals, with a dominant breeding pair and male and female subordinates. While all male and female group members sing duet and chorus song, a male, once it has reached the dominant position in the group, sings an additional type of song that comprises a distinct and large syllable repertoire. Here we show for both types of male – female comparisons a male-biased sex difference in neuroanatomy of areas of the song production pathway (HVC and RA) that does not correlate with the observed polymorphism in song behaviour. In contrast, in situ hybridisation of mRNA of selected genes expressed in the song nucleus HVC reveals a gene expression pattern that is either similar between sexes in female – subordinate male comparisons or female-biased in female – dominant male comparisons. Thus, the polymorphic gene expression pattern would fit the sex- and status-related song behaviour. However, this implies that once a male has become dominant it produces the duetting song with a different neural phenotype than subordinate males

Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model

Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth.We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926.Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C), no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival.IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting

The Transcription Factor YY1 Is a Substrate for Polo-Like Kinase 1 at the G2/M Transition of the Cell Cycle

Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate