Transcriptional Regulation of the Intestinal Cancer Stem Cell Phenotype

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Current treatments include surgery and chemotherapy, but disease recurrence occurs frequently. The continuous renewal of intestinal epithelium relies on the presence of intestinal stem cells that are also at the origin of CRC and contribute to therapy resistance and metastatic dissemination. Several nuclear signaling pathways and transcription factors regulate both intestinal cell homeostasis and tumorigenesis. However, the transcriptional events that govern the emergence of aggressive therapy-resistant cancer stem cells are still poorly defined. This review summarizes the relevance of transcription factors in intestinal stem cell biology and their involvement in colon cancer development and drug resistance

Chapter Métiers, effort and catches of a Mediterranean small-scale coastal fishery: the case of the gulf of Lion Marine Natural Parc

In the context of current fisheries crisis, this study aimed describing the characteristics of the artisanal fisheries in the Gulf of Lion Marine Natural Park located north-western Mediterranean. Catch Per Unit Effort and fishing effort were described on a spatio-temporal scale. Data were collected through questionnaires to fishers at landing sites for a one-year between 2019 and 2020. The most frequently used métiers were the hake gillnet and the sparids trammel net and gillnet, targeting two predominant species: hake (Merluccius merluccius) and gilthead seabream (Sparus aurata)

UPDATING AND TESTING THE PASRR SCREEN IN KANSAS: REAL WORLD IMPLICATIONS

This work is licensed under a Creative Commons Attribution 4.0 International License.Kansas is updating the PASRR (Preadmission Screen and Resident Review) Level 1 screen per new guidance from the PASRR Technical Assistance Committee (PTAC), via a partnership between the State and university researchers. PTAC has directed states to screen for undiagnosed serious and persistent mental illness (SPMI) and also recommends screening for substance related disorders. Stakeholders were engaged through advisory workgroups and a content validity expert panel. These activities led to the creation of a revised PASRR Level-1 screen, but stakeholders also raised several concerns. PASRR law does not require Level-1 assessors to have professional training in mental health diagnoses or treatment, yet new guidelines asks them to screen for undiagnosed SPMI. Further, there are apparent discrepancies between these new guidelines and PASRR Level-2 criteria. Finally, current information management systems are not equipped to handle the higher security protocols associated substance use disorders. The draft instrument was tested with a sample of 103 nursing facility applicants by trained PASRR assessors and inter-rater reliability (IRR) was tested via a standardized vignette with 14 trained PASRR assessors. Only 3% of actual NF applicants were identified as possibly having an undiagnosed SPMI and only 43% of assessors correctly identified symptoms of a suspected SPMI in the standardized vignette, indicating poor validity and reliability in assessing for undiagnosed SPMI during the Level-1 screen. New PASRR guidelines may better ensure that nursing facility residents receive appropriate care for SPMI, however, there are many challenges to ensuring an accurate screen and supporting successful implementation

Expression and role of RIP140/NRIP1 in chronic lymphocytic leukemia

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ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression

SummaryWe show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5−/−;bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in Adamts5−/−;bt/bt webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments

The RIP140 Gene Is a Transcriptional Target of E2F1

RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases

Regulation of intestinal homeostasis and tumorigenesis by the transcriptional coregulator RIP140

International audienceColon cancer frequently results from mutations that constitutively activate the Wnt signaling pathway, a major target being the tumor suppressor gene adenomatous polyposis coli (APC). We recently identified the transcription factor RIP140 as a new inducer of APC gene transcription that inhibits colon cancer cell growth and impedes the Wnt signaling pathway by reducing β-catenin activation

NRIP1 (nuclear receptor interacting protein 1)

International audienceReview on NRIP1, with data on DNA, on the protein encoded, and where the gene is implicated