421 research outputs found

    Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer

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    Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.Cancer Research UK C8221/A30904 C8221/A29017World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeGerman Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR)Netherlands Government Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain)Junta de AndaluciaPrincipality of AsturiasRegional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology-ICO (Spain)Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden)UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/

    Internuclear gene silencing in Phytophthora infestans is established through chromatin remodelling

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    In the plant pathogen Phytophthora infestans, nuclear integration of inf1 transgenic DNA sequences results in internuclear gene silencing of inf1. Although silencing is regulated at the transcriptional level, it also affects transcription from other nuclei within heterokaryotic cells of the mycelium. Here we report experiments exploring the mechanism of internuclear gene silencing in P. infestans. The DNA methylation inhibitor 5-azacytidine induced reversion of the inf1-silenced state. Also, the histone deacetylase inhibitor trichostatin-A was able to reverse inf1 silencing. inf1-expression levels returned to the silenced state when the inhibitors were removed except in non-transgenic inf1-silenced strains that were generated via internuclear gene silencing, where inf1 expression was restored permanently. Therefore, inf1-transgenic sequences are required to maintain the silenced state. Prolonged culture of non-transgenic inf1-silenced strains resulted in gradual reactivation of inf1 gene expression. Nuclease digestion of inf1-silenced and non-silenced nuclei showed that inf1 sequences in silenced nuclei were less rapidly degraded than non-silenced inf1 sequences. Bisulfite sequencing of the endogenous inf1 locus did not result in detection of any cytosine methylation. Our findings suggest that the inf1-silenced state is based on chromatin remodelling

    Cultural molding, shielding, and shoring at Oilco: the role of culture in the integration of routines

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    We explore how organizational culture shapes an organization’s integration and enactment of an external routine that is not a cultural fit. Attending to employees’ use of culture as a repertoire of strategies of action, we found that the use of familiar cultural strategies of action shaped the routine’s artifacts and expectations even before it was performed, a process we call cultural molding. Subsequently, employees drew differently on cultural strategies of action as they performed the routine, generating patterns of workarounds or hindered performances. In response to these patterns, they undertook additional cultural work to either shield their workarounds and protect them from scrutiny or shore up hindered performances. We contribute to the routine dynamics literature by highlighting the effortful cultural work involved in integrating coveted routines, furthering our understanding of routines as truces and the embeddedness of routines.Social Sciences and Humanities Research Council of Canada [Grant 430-2012-195

    Family routines and next-generation engagement in family firms

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    By focusing on the impact of different types of family routines and how they change, this commentary builds on concepts regarding the influence of perceived parental support and psychological control on next-generation engagement in family firms. Drawing on the organizational routines literature and the family studies literature, I propose that attention to family routines, and how these routines change (or not) over time can reveal additional insights regarding next-generation engagement in the family business
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