Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application-0

<p><b>Copyright information:</b></p><p>Taken from "Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application"</p><p>Environmental Health Perspectives 2004;113(2):211-219.</p><p>Published online 23 Sep 2004</p><p>PMCID:PMC1277867.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application-2

<p><b>Copyright information:</b></p><p>Taken from "Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application"</p><p>Environmental Health Perspectives 2004;113(2):211-219.</p><p>Published online 23 Sep 2004</p><p>PMCID:PMC1277867.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application-5

<p><b>Copyright information:</b></p><p>Taken from "Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application"</p><p>Environmental Health Perspectives 2004;113(2):211-219.</p><p>Published online 23 Sep 2004</p><p>PMCID:PMC1277867.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Assessment of <i>SLX4</i> Mutations in Hereditary Breast Cancers

<div><p>Background</p><p><i>SLX4</i> encodes a DNA repair protein that regulates three structure-specific endonucleases and is necessary for resistance to DNA crosslinking agents, topoisomerase I and poly (ADP-ribose) polymerase (PARP) inhibitors. Recent studies have reported mutations in <i>SLX4</i> in a new subtype of Fanconi anemia (FA), FA-P. Monoallelic defects in several FA genes are known to confer susceptibility to breast and ovarian cancers.</p><p>Methods and Results</p><p>To determine if <i>SLX4</i> is involved in breast cancer susceptibility, we sequenced the entire <i>SLX4</i> coding region in 738 (270 Jewish and 468 non-Jewish) breast cancer patients with 2 or more family members affected by breast cancer and no known <i>BRCA1</i> or <i>BRCA2</i> mutations. We found a novel nonsense (c.2469G>A, p.W823*) mutation in one patient. In addition, we also found 51 missense variants [13 novel, 23 rare (MAF<0.1%), and 15 common (MAF>1%)], of which 22 (5 novel and 17 rare) were predicted to be damaging by Polyphen2 (score = 0.65–1). We performed functional complementation studies using p.W823* and 5 <i>SLX4</i> variants (4 novel and 1 rare) cDNAs in a human <i>SLX4</i>-null fibroblast cell line, RA3331. While wild type <i>SLX4</i> and all the other variants fully rescued the sensitivity to mitomycin C (MMC), campthothecin (CPT), and PARP inhibitor (Olaparib) the p.W823* <i>SLX4</i> mutant failed to do so.</p><p>Conclusion</p><p>Loss-of-function mutations in <i>SLX4</i> may contribute to the development of breast cancer in very rare cases.</p></div

Additional file 1: of Comprehensive detection of germline variants by MSK-IMPACT, a clinical diagnostic platform for solid tumor molecular oncology and concurrent cancer predisposition testing

Supplementary Methods and Tables S1-S6. (DOCX 93 kb

Assessment of sustainability of forest management practices on the operational level in northwestern Russia – a case study from the Republic of Karelia

The main aim of the article is to assess the consequences of newly proposed legislative initiative on introducing intensive forest management practices in Russia. Implementation of norms and its effect on sustainable forest management practices have been analysed in this study on one enterprise operating in the Republic of Karelia. This meant modelling of forest growth, clear cuts and regeneration within 100 km radius from the mill for two alternative management scenarios with fixed demand of wood based on current norms and decreasing harvesting age to half from the current. Wood demand of the enterprise, structure and accessibility of forest resources, i.e. forest road infrastructure were taken into account in the analysis. Both forest management scenarios decreased the total growing stock significantly, and therefore considered as non-sustainable practices. In addition, forest age structure was more uneven for both scenarios at the end of the simulation period. Comparison of two alternative management practices showed that the implementation of intensive forest management in Russia requires new norms that would be based on principles of sustainable forest management.201

Identification of the nonsense<i>SLX4</i> variant and evaluation of pathogenicity of the <i>SLX4</i> variants by complementation assay.

<p>(A) Sanger sequence traces for DNA extracted from whole blood and breast tumor of the patient with the c.2469G>A (p.W823*) <i>SLX4</i> mutation (NCBI Refseq NM_032444.2). (B) Anti-HA immunoblot showing expression of HA-tagged SLX4 variants in RA3331/E6E7/hTERT cells. Alpha-tubulin serves as loading control. (C)∼(E) Cell survival assays of the RA3331/E6E7/hTERT cell lines expressing indicated SLX4 variants in response to MMC (C), CPT (D) and the PARP inhibitor, Olaparib (E). RA3331/E6E7/hTERT fibroblast cell lines expressing empty vector, wild type SLX4 and indicated SLX4 variants were treated in triplicate with increasing concentrations of MMC (0–100 nM), CPT (0–16 nM) and Olaparib (0–50 µM). After 8 days in culture, the cell number was determined using a Coulter counter. The number of cells at each drug concentration was divided by the number of cells in the untreated sample to calculate the percentage of cell survival. The error bars indicate standard deviations based on three replicates.</p

Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies

<div><p>The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near <em>LPXN</em>, (P_LYM = 3.89×10⁻⁸, OR = 1.29) and rs948562 (P_LYM = 5.85×10⁻⁷, OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P_NHL = 5.72×10⁻⁷) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P_FL = 2.69×10⁻¹², OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.</p> </div

Quantile–quantile plots.

<p>Quantile–quantile (QQ) plots for (A) LYM, (B) NHL, (C) FL, (D) DLBCL. The X-axis represents expected −log₁₀(P) and the Y-axis represents −log₁₀(P) from logistic regression. Genomic inflation factor λ for LYM, NHL, FL and DLBCL was 1.09, 1.07, 1.04 and 1.04 respectively.</p