Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP (carbohydrate responsive element binding protein) locus and HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63599) and the UK Biobank (N=59220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (beta, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P<0.0001), but not significantly among the lowest SSB consumers (P=0.81; P-Diff<0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (beta, 0.06 [95% CI, 0.02-0.09] In-mg/dL per allele, P=0.001) but not the lowest SSB consumers (P=0.84; P-Diff=0.0005).CONCLUSIONS: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations.Clinical epidemiolog

Mo-nu-menten van vernieuwing

De ontwikkeling van ijzer en staal toont een groot aantal momenten waarop nieuwe technieken worden toegepast. Door de inspirerende en anticiperende wijze waarop dat gebeurt, kunnen de produkten nu worden beschouwd als monumenten van hun tijd. Dit is vooral van belang voor het inzicht in de ontwikkeling van het technisch concept. Het verlichte materiaal stimuleerde een zelfstandiger ontwerphouding, los van conventies en tradities. De aard van de bouwopdrachten en de signatuur van actuele bedrijvigheden die om een toegesneden behuizing vragen (opkomst industrie, grootkapitaal, werkplaatsen, fabrieken, pakhuizen etc.) bepalen mede de veranderende gedaante van de 'zelfkant' van de architectuur. Een nieuwe taal dient zich aan

Woningbouw - staaltjes van vernuft

Vanaf het midden van de 1ge eeuw wordt staal toegepast in de woningbouw. Bij de eerste experimenten verving staal alleen de traditionele materialen, zonder gebruik te maken van de specifieke eigenschappen ervan. Staal werd niet gezien als een bijdrage aan de kwaliteit en de duurzaamheid. Woningen betekenen bezit en status en hebben als zodanig vaak een emotionele waarde. Staal wordt gemakkelijk geassocieerd met snel, tijdelijk en goedkoop. Bouwbedrijven die van huis uit vertrouwd zijn met metselen en timmeren gedogen staal eigenlijk alleen als wapening in vloeren en lateien.Producenten van industrieel vervaardigde woningen in landen als Japan en Frankrijk begrepen al vroeg dat er een geheel eigen markt is in de nieuwbouwsector. Dergelijke ondernemers buitten de mogelijkheden uit van de prefab bouwwijze en pasten staal zo toe, dat de aard en de status van de woning niet werden aangetast (afb. 16.1). Initiatieven in de Verenigde Staten en Engeland bleken eveneens succesvol

Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: Recent Evidence and Clinical Implications

Over the past 20 years, high-risk human papillomavirus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer

DESA1002 'Continuous City' David Luc

My site is located in Spain, Madrid on a corner lot of Calle Mayor st. The majority of the surrounding buildings are retail stores on the ground floor with apartments situated on top. My design proposal focuses on motorcycle hire and purchase, the supply of motorcycle goods as well as hospitality services. The building design is 5 split floors dividing the numerous services. The ground floor focuses on the hospitality services and the above on the retail and sales facilities. The hospitality services include a cafe with an outdoor terrace for consumers. The cafe is for customers who are waiting for their bike to be serviced or even external customers just wanting a coffee. My structure contains specific features which enhance the overall design in relation to aesthetics and function. The split levels generate greater ceiling heights and optional views to levels above and below. These views create excitement and a sense of adventure. Wide glazed windows allow sufficient solar access and vertical louvers permit solar control. Internally i have created a race track theme which can be identified in the circulation from floor to floor. Rather than having a single lift to all floors, stairs located at different points on each floor encourage customers to venture throughout the building and experience the unique structure. This theme combined with the split level differentiates from a general flat floor plan as it provides variety when circulating throughout the building as well as creating numerous views which can prove to be exiting and adventurous

Double reporting and second opinion in head and neck pathology

Contains fulltext : 137821.pdf (publisher's version ) (Closed access