Relationship Between Climatic Factors and Distribution of Pratylenchus spp. in the Dryland Wheat-Production Areas of Eastern Washington

Field surveys were conducted by collecting soil samples to estimate nematode densities in soil from winter wheat, spring wheat, spring barley, and spring legumes (lentil, chickpea, and pea) fields during 2010 and 2011. Pratylenchus spp. were observed in 60% of sampled fields. However, nematodes were detected in nearly all of the survey fields in high numbers where crops were grown every year. To identify climatic variables associated with density of Pratylenchus spp. in soil, correlation and regression analyses were performed using climate data of survey sites from 1979 to 2010. Fifty-seven climate variables were significantly correlated with densities of Pratylenchus spp. All precipitation variables were significantly positively correlated with nematode abundance. Summer maximum air temperature was negatively correlated and winter minimum air temperature was positively correlated with nematode densities. In addition, both years’ nematode densities were significantly correlated with cropping intensity. Five multivariate regression models for 2010 and seven models for 2011 nematode abundance levels were developed. The majority of the climate variables selected in the models were related to precipitation. Knowledge of root-lesion nematode distribution in the dryland region of eastern Washington and associated climate variables may be helpful to determine risk and apply management practices to minimize crop damage

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation

Introduction: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis. Methods: GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries. Results: In our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10 −11 ), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10 −6 ) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R 2 = 0.51 on univariable analysis, adjusted R 2 = 0.62 after also including latitude); latitude also made an independent contribution. Conclusions: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker

Relationship Between Climatic Factors and Distribution of Pratylenchus spp. in the Dryland Wheat-Production Areas of Eastern Washington

Field surveys were conducted by collecting soil samples to estimate nematode densities in soil from winter wheat, spring wheat, spring barley, and spring legumes (lentil, chickpea, and pea) fields during 2010 and 2011. Pratylenchus spp. were observed in 60% of sampled fields. However, nematodes were detected in nearly all of the survey fields in high numbers where crops were grown every year. To identify climatic variables associated with density of Pratylenchus spp. in soil, correlation and regression analyses were performed using climate data of survey sites from 1979 to 2010. Fifty-seven climate variables were significantly correlated with densities of Pratylenchus spp. All precipitation variables were significantly positively correlated with nematode abundance. Summer maximum air temperature was negatively correlated and winter minimum air temperature was positively correlated with nematode densities. In addition, both years' nematode densities were significantly correlated with cropping intensity. Five multivariate regression models for 2010 and seven models for 2011 nematode abundance levels were developed. The majority of the climate variables selected in the models were related to precipitation. Knowledge of root-lesion nematode distribution in the dryland region of eastern Washington and associated climate variables may be helpful to determine risk and apply management practices to minimize crop damage