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Sökning: WFRF:(James Paul A.) > (2020)

  • Resultat 11-13 av 13
  • Föregående 1[2]
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  • Barrett, Scott, et al. (författare)
  • Social dimensions of fertility behavior and consumption patterns in the Anthropocene
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 117:12, s. 6300-6307
  • Tidskriftsartikel (refereegranskat)abstract
    • We consider two aspects of the human enterprise that profoundly affect the global environment: population and consumption. We show that fertility and consumption behavior harbor a class of externalities that have not been much noted in the literature. Both are driven in part by attitudes and preferences that are not egoistic but socially embedded; that is, each household's decisions are influenced by the decisions made by others. In a famous paper, Garrett Hardin [G. Hardin, Science 162, 1243-1248 (1968)] drew attention to overpopulation and concluded that the solution lay in people abandoning the freedom to breed. That human attitudes and practices are socially embedded suggests that it is possible for people to reduce their fertility rates and consumption demands without experiencing a loss in wellbeing. We focus on fertility in sub-Saharan Africa and consumption in the rich world and argue that bottom-up social mechanisms rather than top-down government interventions are better placed to bring about those ecologically desirable changes.
  • Bosse, Yohan, et al. (författare)
  • Transcriptome-wide association study reveals candidate causal genes for lung cancer
  • 2020
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 146:7, s. 1862-1878
  • Tidskriftsartikel (refereegranskat)abstract
    • We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.
  • Gallagher, Laura A., et al. (författare)
  • Impaired Alanine Transport or Exposure to D-Cycloserine Increases the Susceptibility of MRSA to beta-lactam Antibiotics
  • 2020
  • Ingår i: Journal of Infectious Diseases. - OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 221:6, s. 1006-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Prolonging the clinical effectiveness of beta-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted D-cycloserine (DCS) transporter gene cycA resensitized methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics. The cycA mutation also resulted in hypersusceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and D-alanine ligase required for D-alanine incorporation into cell wall peptidoglycan. Alanine transport was impaired in the cycA mutant, and this correlated with increased susceptibility to oxacillin and DCS. The cycA mutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal D-ala-D-ala and reduced peptidoglycan cross-linking, prompting us to investigate synergism between beta-lactams and DCS. DCS resensitized MRSA to beta-lactams in vitro and significantly enhanced MRSA eradication by oxacillin in a mouse bacteremia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to beta-lactam antibiotics.
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  • Resultat 11-13 av 13
  • Föregående 1[2]
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