Late biological effects of heavy charged particles: Cataracts, vascular injury and life shortening in mice

Risks associated with extended habitation in a space environment, particularly hazards to space workers that might result from exposure to high energy heavy ion particles (HZE), were studied. Biological effects of HZE were investigated in mice to assess their potential adverse health hazards. The potential effects of HZE particles on the crystalline lens of the eye and the carcinogenic effects and blood vessel (vascular) damage from radiation were evaluated by a risk assessment. Animal experiments to evaluate dose response relationships for tumor induction/promotion and for vascular injury were introduced. Cataract productions and preliminary results on cacinogenic and vascular effects are presented for perspective

Pengaruh Kepuasan Kerja Dan Organizational Citizenship Behavior Terhadap Stres Kerja Dan Retensi Karyawan Di PT Multi Auto Intrawahana Pekanbaru

The research was conducted at PT. Multi Auto Intrawahana Pekanbaru. The purpose of this study was to determine the effect of job satisfaction and Organizational Citizenship Behavior (OCB) against work stress and its impact on the retention of employees at PT. Multi Auto Intrawahana Pekanbaru. Total population in this study were 53 employees and a sample is taken from the entire population of 53 employees. The determination of the sample using census method or technique of total sampling is a sampling technique that is done by taking the entire population. The results of the study of job satisfaction significant positive effect on employee retention, Organizational Citizenship Behavior (OCB) has no effect on employee retention, job stress significant negative effect on employee retention, job satisfaction significant negative effect on job stress of employees and Organizational Citizenship Behavior (OCB) negative effect significantly to the stress of employees of PT Multi Auto Intrawahana Pekanbaru. Advice can be given that the leaders should provide equitable opportunities for all employees in career development, to employees in order to always maintain good communication and continue to think positively with each other and the company should be able to pass training on cooperation and responsibility to cultivate an attitude and awareness of responsibility and cooperation on the employee

Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in humanDPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease

High grade B-cell gastric lymphoma with complete pathologic remission after eradication of helicobacter pylori infection: Report of a case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Treatment of primary gastric diffuse large B-cell lymphoma is still controversial. The treatment of localized disease was based on surgery alone, or followed by chemotherapy and/or radiotherapy. High-grade gastric lymphomas are generally believed to be <it>Helicobacter pylori </it>(HP)-independent growing tumors. However a few cases of regression of high-grade gastric lymphomas after the cure of <it>Helicobacter pylori </it>infection had been described.</p> <p>Case presentation</p> <p>We report here a case with primary diffuse large B-cell lymphoma that showed a complete pathologic remission after HP eradication and we reviewed the literature. A computerized literature reach through Medline, Cancerlit and Embase were performed, applying the words: high grade gastric lymphoma, or diffuse large B cell, MALT gastric lymphoma, DLBCLL (MALT) lymphoma and Helicobacter. Articles and abstracts were also identified by back-referencing from original and relevant papers. Selected for the present review were papers published in English before January 2007.</p> <p>Conclusion</p> <p>Forty two cases of primary high grade gastric lymphoma that regressed with anti HP treatment were found. There were anedoctal cases reported and patients belonging to prospective studies; four trials studied the effect of eradication of <it>Helicobacter pylori</it> as first line therapy in high grade gastric lymphoma: 22 of a total of 38 enrolled patients obtained complete remission. Depth of gastric wall infiltration and clinical stage were important factors to predict the response to antibiotic therapy. Our case and the review of the literature show that high-grade transformation is not necessarily associated with the loss HP dependence. In early stage, for high-grade B-cell HP-positive gastric lymphomas, given the limited toxicity of anti-HP therapy, this treatment may be considered as one of the first line treatment options.</p

Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model

Purpose: Exposure to heavy-ion radiation is considered a critical health risk on long-term space missions. The developing central nervous system (CNS) is a highly radiosensitive tissue; however, the biological effects of heavy-ion radiation, which are greater than those of low-linear energy transfer (LET) radiation, are not well studied, especially in vivo in intact organisms. Here, we examined the effects of iron-ions on the developing CNS using vertebrate organism, fish embryos of medaka (Oryzias latipes)

Risks due to X-ray Flares during Astronaut Extravehicular Activity

Solar hard X-ray flares can expose astronauts on lunar and deep space extravehicular activities (EVAs) to dangerous acute biological doses. We combine calculations of radiative transfer through shielding materials with subsequent transfer through tissue to show that hazardous doses, taken as >= 0.1 Gy, should occur with a probability of about 10% per 100 hours of accumulated EVA inside current spacesuits. The rapid onset and short duration of X-ray flares and the lack of viable precursor events require strategies for quick retreat, in contrast to solar proton events, which usually take hours to deliver significant fluence and can often be anticipated by flares or other light-speed precursors. Our results contrast with the view that only particle radiation poses dangers for human space exploration. Heavy-element shields provide the most efficient protection from X-ray flares, since X-rays produce no significant secondary radiation. We calculate doses due to X-ray flares behind aluminum shields and estimate the required shield masses to accompany EVA rovers.Comment: 8 pages, 2 figures; to be published in Space Weathe

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets

Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor (PPARγ) are disrupted by retinal disease-associated mutations

Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the Nuclear Receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of PPARγ/NR1C3 and TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARαNR1C1 or PPARδNR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRβ that have potential importance in retinal development and disease

Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies

IntroductionMost human mammary epithelial cells (HMEC) cultured from histologically normal breast tissues enter a senescent state termed stasis after 5 to 20 population doublings. These senescent cells display increased size, contain senescence associated beta-galactosidase activity, and express cyclin-dependent kinase inhibitor, p16INK4A (CDKN2A; p16). However, HMEC grown in a serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that are capable of long-term growth and are susceptible to genomic instability. We investigated whether ionizing radiation, which increases breast cancer risk in women, affects the rate of vHMEC outgrowth.MethodsPre-stasis HMEC cultures were exposed to 5 to 200 cGy of sparsely (X- or gamma-rays) or densely (1 GeV/amu 56Fe) ionizing radiation. Proliferation (bromodeoxyuridine incorporation), senescence (senescence-associated beta-galactosidase activity), and p16 expression were assayed in subcultured irradiated or unirradiated populations four to six weeks following radiation exposure, when patches of vHMEC became apparent. Long-term growth potential and p16 promoter methylation in subsequent passages were also monitored. Agent-based modeling, incorporating a simple set of rules and underlying assumptions, was used to simulate vHMEC outgrowth and evaluate mechanistic hypotheses.ResultsCultures derived from irradiated cells contained significantly more vHMEC, lacking senescence associated beta-galactosidase or p16 expression, than cultures derived from unirradiated cells. As expected, post-stasis vHMEC cultures derived from both unirradiated and irradiated cells exhibited more extensive methylation of the p16 gene than pre-stasis HMEC cultures. However, the extent of methylation of individual CpG sites in vHMEC samples did not correlate with passage number or treatment. Exposure to sparsely or densely ionizing radiation elicited similar increases in the numbers of vHMEC compared to unirradiated controls. Agent-based modeling indicated that radiation-induced premature senescence of normal HMEC most likely accelerated vHMEC outgrowth through alleviation of spatial constraints. Subsequent experiments using defined co-cultures of vHMEC and senescent cells supported this mechanism.ConclusionsOur studies indicate that ionizing radiation can promote the outgrowth of epigenetically altered cells with pre-malignant potential