The zinc finger transcription factor PW1/PEG3 restrains murine beta cell cycling

Aims/hypothesis: Pw1 or paternally-expressed gene 3 (Peg3) encodes a zinc finger transcription factor that is widely expressed during mouse embryonic development and later restricted to multiple somatic stem cell lineages in the adult. The aim of the present study was to define Pw1 expression in the embryonic and adult pancreas and investigate its role in the beta cell cycle in Pw1 wild-type and mutant mice. Methods: We analysed PW1 expression by immunohistochemistry in pancreas of nonpregant and pregnant mice and following injury by partial duct ligation. Its role in the beta cell cycle was studied in vivo using a novel conditional knockout mouse and in vitro by lentivirus-mediated gene knockdown. Results: We showed that PW1 is expressed in early pancreatic progenitors at E9.5 but becomes progressively restricted to fully differentiated beta cells as they become established after birth and withdraw from the cell cycle. Notably, PW1 expression declines when beta cells are induced to proliferate and loss of PW1 function activates the beta cell cycle. Conclusions/interpretation: These results indicate that PW1 is a co-regulator of the beta cell cycle and can thus be considered a novel therapeutic target in diabetes

Community standards for open cell migration data

Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration

Publishing and sharing multi-dimensional image data with OMERO

Imaging data are used in the life and biomedical sciences to measure the molecular and structural composition and dynamics of cells, tissues, and organisms. Datasets range in size from megabytes to terabytes and usually contain a combination of binary pixel data and metadata that describe the acquisition process and any derived results. The OMERO image data management platform allows users to securely share image datasets according to specific permissions levels: data can be held privately, shared with a set of colleagues, or made available via a public URL. Users control access by assigning data to specific Groups with defined membership and access rights. OMERO’s Permission system supports simple data sharing in a lab, collaborative data analysis, and even teaching environments. OMERO software is open source and released by the OME Consortium at www.openmicroscopy.org

A pathway in quiescent cells that controls p27 Kip1 stability, subcellular localization, and tumor suppression

We have created two knock-in mouse models to study the mechanisms that regulate p27 in normal cells and cause misregulation of p27 in tumors: p27 S10A , in which Ser10 is mutated to Ala; and p27 CK − , in which point mutations abrogate the ability of p27 to bind cyclins and CDKs. These two mutant alleles identify steps in a pathway that controls the proteasomal degradation of p27 uniquely in quiescent cells: Dephosphorylation of p27 on Ser10 inhibits p27 nuclear export and promotes its assembly into cyclin-CDK complexes, which is, in turn, necessary for p27 turnover. We further show that Ras-dependent lung tumorigenesis is associated with increased phosphorylation on Ser10 and cytoplasmic mislocalization of p27. Indeed, we find that p27 S10A is refractory to Ras-induced cytoplasmic translocation and that p27 S10A mice are tumor resistant. Thus, phosphorylation of p27 on Ser10 is an important event in the regulation of the tumor suppressor function of p27

Objectively measured physical activity during pregnancy: A study in obese and overweight women

Background Obese and overweight women may benefit from increased physical activity (PA) during pregnancy. There is limited published data describing objectively measured PA in such women. Methods A longitudinal observational study of PA intensity, type and duration using objective and subjective measurement methods. Fifty five pregnant women with booking body mass index (BMI) ≥ 25 kg/m2 were recruited from a hospital ultrasound clinic in North East England. 26 (47%) were nulliparous and 22 (40%) were obese (BMI ≥ 30 kg/m2). PA was measured by accelerometry and self report questionnaire at 13 weeks, 26 weeks and/or 36 weeks gestation. Outcome measures were daily duration of light, moderate or vigorous activity assessed by accelerometry; calculated overall PA energy expenditure, (PAEE), and PAEE within four domains of activity based on self report. Results At median 13 weeks gestation, women recorded a median 125 mins/day light activity and 35 mins/day moderate or vigorous activity (MVPA). 65% achieved the minimum recommended 30 mins/day MVPA. This proportion was maintained at 26 weeks (62%) and 36 weeks (71%). Women achieving more than 30 mins/day MVPA in the first trimester showed a significant reduction in duration of MVPA by the third trimester (11 mins/day, p = 0.003). Walking, swimming and floor exercises were the most commonly reported recreational activities but their contribution to estimated energy expenditure was small. Conclusion Overweight and obese pregnant women can achieve and maintain recommended levels of PA throughout pregnancy. Interventions to promote PA should target changes in habitual activities at work and at home, and in particular walking.The study was supported jointly by Newcastle University and the Directorate of Women’s Services, Royal Victoria Infirmary, Newcastle Upon Tyne, UK

Objectively measured physical activity during pregnancy: a study in obese and overweight women.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Obese and overweight women may benefit from increased physical activity (PA) during pregnancy. There is limited published data describing objectively measured PA in such women. METHODS: A longitudinal observational study of PA intensity, type and duration using objective and subjective measurement methods. Fifty five pregnant women with booking body mass index (BMI) ≥ 25 kg/m2 were recruited from a hospital ultrasound clinic in North East England. 26 (47%) were nulliparous and 22 (40%) were obese (BMI ≥ 30 kg/m2). PA was measured by accelerometry and self report questionnaire at 13 weeks, 26 weeks and/or 36 weeks gestation. Outcome measures were daily duration of light, moderate or vigorous activity assessed by accelerometry; calculated overall PA energy expenditure, (PAEE), and PAEE within four domains of activity based on self report. RESULTS: At median 13 weeks gestation, women recorded a median 125 mins/day light activity and 35 mins/day moderate or vigorous activity (MVPA). 65% achieved the minimum recommended 30 mins/day MVPA. This proportion was maintained at 26 weeks (62%) and 36 weeks (71%). Women achieving more than 30 mins/day MVPA in the first trimester showed a significant reduction in duration of MVPA by the third trimester (11 mins/day, p = 0.003). Walking, swimming and floor exercises were the most commonly reported recreational activities but their contribution to estimated energy expenditure was small. CONCLUSION: Overweight and obese pregnant women can achieve and maintain recommended levels of PA throughout pregnancy. Interventions to promote PA should target changes in habitual activities at work and at home, and in particular walking.Published versio

Metadata management for high content screening in OMERO

High content screening (HCS) experiments create a classic data management challenge—multiple, large sets of heterogeneous structured and unstructured data, that must be integrated and linked to produce a set of “final” results. These different data include images, reagents, protocols, analytic output, and phenotypes, all of which must be stored, linked and made accessible for users, scientists, collaborators and where appropriate the wider community. The OME Consortium has built several open source tools for managing, linking and sharing these different types of data. The OME Data Model is a metadata specification that supports the image data and metadata recorded in HCS experiments. Bio-Formats is a Java library that reads recorded image data and metadata and includes support for several HCS screening systems. OMERO is an enterprise data management application that integrates image data, experimental and analytic metadata and makes them accessible for visualization, mining, sharing and downstream analysis. We discuss how Bio-Formats and OMERO handle these different data types, and how they can be used to integrate, link and share HCS experiments in facilities and public data repositories. OME specifications and software are open source and are available at https://www.openmicroscopy.org

What are the health benefits of active travel? A systematic review of trials and cohort studies.

BACKGROUND: Increasing active travel (primarily walking and cycling) has been widely advocated for reducing obesity levels and achieving other population health benefits. However, the strength of evidence underpinning this strategy is unclear. This study aimed to assess the evidence that active travel has significant health benefits. METHODS: The study design was a systematic review of (i) non-randomised and randomised controlled trials, and (ii) prospective observational studies examining either (a) the effects of interventions to promote active travel or (b) the association between active travel and health outcomes. Reports of studies were identified by searching 11 electronic databases, websites, reference lists and papers identified by experts in the field. Prospective observational and intervention studies measuring any health outcome of active travel in the general population were included. Studies of patient groups were excluded. RESULTS: Twenty-four studies from 12 countries were included, of which six were studies conducted with children. Five studies evaluated active travel interventions. Nineteen were prospective cohort studies which did not evaluate the impact of a specific intervention. No studies were identified with obesity as an outcome in adults; one of five prospective cohort studies in children found an association between obesity and active travel. Small positive effects on other health outcomes were found in five intervention studies, but these were all at risk of selection bias. Modest benefits for other health outcomes were identified in five prospective studies. There is suggestive evidence that active travel may have a positive effect on diabetes prevention, which may be an important area for future research. CONCLUSIONS: Active travel may have positive effects on health outcomes, but there is little robust evidence to date of the effectiveness of active transport interventions for reducing obesity. Future evaluations of such interventions should include an assessment of their impacts on obesity and other health outcomes

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10 −54 ) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10 −19 ). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy. © 2018, The Author(s).Peer reviewe