Discovery and functional annotation of PRSS1 promoter variants in chronic pancreatitis

Recently, our resequencing of the promoter region of PRSS1 in French Caucasian individuals led to the identification of a functional variant (c.-204C > A) that is in perfect linkage disequilibrium with the “chronic pancreatitis (CP)-protective” PRSS1 c.-408C > T variant. Here, we extended the resequencing to 626 French Caucasians (242 idiopathic CP patients and 384 controls). We discovered three additional variants (c.-184G > A, c.-173C > T, and c.-147C > T), each being found only once in either patients or controls. We analyzed these three variants, together with a known PRSS1 promoter variant (c.-30_-28delTCC) long considered to be causative for CP, by luciferase promoter reporter assay in AR42J cells treated with dexamethasone. This analysis revealed that c.-30_-28delTCC resulted in reduced rather than increased PRSS1 gene expression, suggesting that it is not a CP risk factor as originally claimed. We provide evidence that c.-147C > T probably confers protection against CP by reducing the affinity of an ATF4 transcription factor binding site

Exclusion from the Golgi and very low levels of HTLV-2 Tax ubiquitination do not prevent IKK-gamma/NEMO relocalization and NF-κB activation

International audiencen.

Predominant role of Tax sumoylation in Tax-induced NF-kB activation in T cells

International audiencen.

HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner

HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX genes have also been linked to oncogenesis and HOXA1 has been described to be active in several cancers, including breast cancer. Through a proteome-wide interaction screening, we previously identified the TNFR-associated proteins RBCK1/HOIL-1 and TRAF2 as HOXA1 interactors suggesting that HOXA1 is functionally linked to the TNF/NF-κB signaling pathway. Here, we reveal a strong positive correlation between expression of HOXA1 and of members of the TNF/NF-κB pathway in breast tumor datasets. Functionally, we demonstrate that HOXA1 can activate NF-κB and operates upstream of the NF-κB inhibitor IκB. Consistently, we next demonstrate that the HOXA1-mediated activation of NF-κB is non-transcriptional and that RBCK1 and TRAF2 influences on NF-κB are epistatic to HOXA1. We also identify an 11 Histidine repeat and the homeodomain of HOXA1 to be required both for RBCK1 and TRAF2 interaction and NF-κB stimulation. Finally, we highlight that activation of NF-κB is crucial for HOXA1 oncogenic activity

3D advanced integration technology for heterogeneous systems

International audience3D integration technology is nowadays mature enough, offering today further system integration using heterogeneous technologies, with already many different industrial successes (Imagers, 2.5D Interposers, 3D Memory Cube, etc.). CEA-LETI has been developing for a decade 3D integration, and have pursued research in both directions: developing advanced 3D technology bricks (TSVs, µ-bumps, Hybrid Bonding, etc), and designing advanced 3D circuits as pioneer prototypes. In this paper, a short overview of some recent advanced 3D technology results is presented, including some latest 3D circuit's description

Low levels of HTLV-2 Tax conjugation to ubiquitin and SUMO do not impede Tax-mediated activation of NF-κB

International audienc

Lokalmeteorologiska förhållanden i Västra Ängby, Knivsta : förstudie /

<p>Variation of pollen beetle abundance along within-field (A) and between-field (B) transects as a function of distance (km) to woodland edges. (A) Number of pollen beetles per sampling point within two different OSR fields (fields in complex site, C). (B) Mean number of pollen beetles per field in three transects (in zones S, for simple landscape, and HC, for highly complex landscape). Abundance were measured on 10 OSR plants at each sampling point during three (A) or four (B) consecutive weeks (dates 1 to 4). Trans: Transect.</p

Demographic, socioeconomic, and sociocultural factors associated with any breastfeeding in homeless mothers

In high‐income countries, breastfeeding has been shown to be positively associated with socioeconomic position. However, less is known about breastfeeding practices and their associated factors among extremely disadvantaged populations. We aimed to assess the associations of cultural origins and socioeconomic factors with any breastfeeding initiation and duration in homeless families. We analyzed data from 456 children aged 6 months to 5 years from the cross‐sectional ENFAMS survey, conducted in 2013 among a random sample of homeless families in shelters in the Greater Paris area. Data were collected by bilingual interviewers in 17 languages. Four nested multivariable robust Poisson regression models were run in a hierarchical framework to determine the factors associated with breastfeeding initiation and with any breastfeeding for 6 months or more. Most of the children (86.0%) had previously been or were currently being breastfed at the time of the survey; 58.9% were fed with breast milk ≥6 months. A higher maternal age and African origin were positively associated with breastfeeding ≥6 months, although the relation to the region of origin was moderated by education level. Migration to escape war, unrest or other violence and the child's birth in France were inversely associated with breastfeeding ≥6 months. Any breastfeeding by these homeless mothers seems influenced predominantly by their cultural origin and complicated by a difficult migration trajectory. The possible influence of poor material circumstances and cumulative hardship should encourage interventions targeted at homeless mothers that emphasize social/family support with a commitment to improving the family's living conditions