Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Using concept mapping in the development of the EU-PAD framework (EUropean-Physical Activity Determinants across the life course): a DEDIPAC-study.

BACKGROUND: A large proportion of European children, adults and older adults do not engage in sufficient physical activity (PA). Understanding individual and contextual factors associated with PA behaviours is essential for the identification and implementation of effective preventative environments, policies, and programmes that can promote an active lifestyle across life course and can potentially improve health. The current paper intends to provide 1) a multi-disciplinary, Pan-European and life course view of key determinants of PA behaviours and 2) a proposal of how these factors may cluster. METHODS: After gathering a list of 183 potential PA behaviours-associated factors and a consensus meeting to unify/consolidate terminology, a concept mapping software was used to collate European experts' views of 106 identified factors for youth (<19 years), adults (19-64 years), and older adults (≥65 years). The analysis evaluated common trends in the clustering of factors and the ratings of the distinct factors' expected modifiability and population-level impact on PA behaviours across the life course. Priority for research was also assessed for each cluster. RESULTS: The concept mapping resulted in six distinct clusters, broadly merged in two themes: 1) the 'Person', which included clusters 'Intra-Personal Context and Wellbeing' and 'Family and Social Economic Status' (42 % of all factors) and 2) the 'Society', which included the remaining four clusters 'Policy and Provision', 'Cultural Context and Media', 'Social Support and Modelling', and 'Supportive Environment' (58 % of all factors). Overall, 25 factors were rated as the most impactful on PA behaviours across the life course and being the most modifiable. They were mostly situated in the 'Intra-Personal Context and Wellbeing' cluster. Furthermore, 16 of them were rated as top priority for research. CONCLUSIONS: The current framework provides a preliminary overview of factors which may account for PA behaviour across the life course and are most relevant to the European community. These insights could potentially be a foundation for future Pan-European research on how these factors might interact with each other, and assist policy makers to identify appropriate interventions to maximize PA behaviours and thus the health of European citizens

Cuznzr-zeolite hybrid grains for DME synthesis: New evidence on the role of metal-acidic features on the methanol conversion step

The assessment of the catalytic performance of “hybrid” metal/zeolite catalysts (based on FER or MFI structure and CuZnZr metal complexes) in the methanol dehydration step to DME has been studied in this work. The results clearly show that there is an important effect of the interaction between metal and acid sites affecting the acid catalyst performances. Additionally, deactivation, studied by means of a Timo-on-Stream (TOS) test, was affected by the type of zeolite structure used for hybrid catalyst preparation. The decrease in DME selectivity can be attributed to the cooperation of metal and acid sites in the production of different compounds (mainly methyl formate and dimethoxy methane) converting methanol and DME. The presence of these compounds (indicating different reaction pathways active) was found to be dependent on the zeolite structure and on the type of co-precipitation medium (water or ethanol) used to prepare the hybrid catalyst

Socio-cultural determinants of physical activity across the life course: a 'Determinants of Diet and Physical Activity' (DEDIPAC) umbrella systematic literature review

Objective Regular physical activity (PA) reduces the risk of disease and premature death. Knowing factors associated with PA might help reducing the disease and economic burden caused by low activity. Studies suggest that socio-cultural factors may affect PA, but systematic overviews of findings across the life course are scarce. This umbrella systematic literature review (SLR) summarizes and evaluates available evidence on socio-cultural determinants of PA in children, adolescents, and adults. Methods This manuscript was drafted following the recommendations of the ‘Preferred Reporting Items for Systematic reviews and Meta-Analyses’ (PRISMA) checklist. The MEDLINE, Web of Science, Scopus, and SPORTDiscus databases were searched for SLRs and meta-analyses (MAs) on observational studies published in English that assessed PA determinants between January 2004 and April 2016. The methodological quality was assessed and relevant information on socio-cultural determinants and any associations with PA was extracted. The available evidence was evaluated based on the importance of potential determinants and the strength of the evidence. Results Twenty SLRs and three MAs encompassing 657 eligible primary studies investigated potential socio-cultural PA determinants, with predominantly moderate methodological quality. Twenty-nine potential PA determinants were identified that were primarily assessed in children and adolescents and investigated the micro-environmental home/household level. We found probable evidence that receiving encouragement from significant others and having a companion for PA were associated with higher PA in children and adolescents, and that parental marital status (living with partner) and experiencing parental modeling were not associated with PA in children. Evidence for the other potential determinants was limited, suggestive, or non-conclusive. In adults, quantitative and conclusive data were scarce. Conclusions A substantial number of SLRs and MAs investigating potential socio-cultural determinants of PA were identified. Our data suggest that receiving social support from significant others may increase PA levels in children and adolescents, whereas parental marital status is not a determinant in children. Evidence for other potential determinants was limited. This was mainly due to inconsistencies in results on potential socio-cultural determinants of PA across reviews and studies

Validity and reliability of a photoelectric cells system for the evaluation of change of direction and lateral jumping abilities in collegiate basketball athletes

The validity and reliability of the Optojump system were investigated for jumping height and flight time in vertical jump tests. Conversely, the purpose of the present study was to investigate the validity and reliability of the Optojump system for measuring contact time and lateral displacement in change of direction and lateral jump tests. Thirty basketball collegiate athletes were tested on two 10 m sprints with a 60° (COD60) or 180° (COD180) change of direction, lateral controlled (CLRJ) and maximal (MLRJ) rebound jump, and lateral countermovement (LCMJ) and squat (LSJ) jump with the concomitant use of two force plates and the Optojump system for the measurement of contact time in COD60, COD180, CLRJ, MLRJ, and lateral jumping distance in all the lateral jump tests. Almost perfect coefficients (r ≥ 0.95) emerged for contact time in COD60, COD180, CLRJ, MLRJ, although a systematic bias was found for COD60 (-0.01 s). Good-to-excellent reliability was found for almost all the measurements of contact time and lateral jumping distance for change of direction and lateral jump tests. Therefore, the use of Optojump system for testing change of direction and lateral jumping abilities should be executed with caution, avoiding misinterpretation of data

The SOS-framework (Systems of Sedentary behaviours): an international transdisciplinary consensus framework for the study of determinants, research priorities and policy on sedentary behaviour across the life course: a DEDIPAC-study.

BACKGROUND: Ecological models are currently the most used approaches to classify and conceptualise determinants of sedentary behaviour, but these approaches are limited in their ability to capture the complexity of and interplay between determinants. The aim of the project described here was to develop a transdisciplinary dynamic framework, grounded in a system-based approach, for research on determinants of sedentary behaviour across the life span and intervention and policy planning and evaluation. METHODS: A comprehensive concept mapping approach was used to develop the Systems Of Sedentary behaviours (SOS) framework, involving four main phases: (1) preparation, (2) generation of statements, (3) structuring (sorting and ranking), and (4) analysis and interpretation. The first two phases were undertaken between December 2013 and February 2015 by the DEDIPAC KH team (DEterminants of DIet and Physical Activity Knowledge Hub). The last two phases were completed during a two-day consensus meeting in June 2015. RESULTS: During the first phase, 550 factors regarding sedentary behaviour were listed across three age groups (i.e., youths, adults and older adults), which were reduced to a final list of 190 life course factors in phase 2 used during the consensus meeting. In total, 69 international delegates, seven invited experts and one concept mapping consultant attended the consensus meeting. The final framework obtained during that meeting consisted of six clusters of determinants: Physical Health and Wellbeing (71% consensus), Social and Cultural Context (59% consensus), Built and Natural Environment (65% consensus), Psychology and Behaviour (80% consensus), Politics and Economics (78% consensus), and Institutional and Home Settings (78% consensus). Conducting studies on Institutional Settings was ranked as the first research priority. The view that this framework captures a system-based map of determinants of sedentary behaviour was expressed by 89% of the participants. CONCLUSION: Through an international transdisciplinary consensus process, the SOS framework was developed for the determinants of sedentary behaviour through the life course. Investigating the influence of Institutional and Home Settings was deemed to be the most important area of research to focus on at present and potentially the most modifiable. The SOS framework can be used as an important tool to prioritise future research and to develop policies to reduce sedentary time