RAD51 restricts DNA over-replication from re-activated origins

Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation

Whose Experiences Do We Understand? Generalizability Considerations When Analyzing Data about Massive Open Online Courses

Massive Open Online Courses (MOOCs) have generated considerable excitement and considerable skepticism since their recent inception (e.g., Kim, 2014; Perna et al., 2014). By fall 2015, approximately 35 million people had participated in 4200 courses offered by over 550 institutions (Shah, 2015). In addition to MOOCs’ potential for expanding access to higher education offerings, scholars have touted their potential for facilitating research about online learning (Eichhorn & Matkin, 2016; Haywood, 2016). However, many questions remain about what participants are actually learning from MOOCs and how researchers can best make use of the huge amount of data the courses generate. In Fall 2014, Oregon State University launched its first Massive Open Online Course (MOOC), Supporting English Language Learners Under New Standards. Funded by the Oregon Department of Education and created in partnership with Stanford University, this course was designed to provide K-12 teachers with specific professional development on fostering English learners’ skills in argumentation, a key practice emphasized in new education standards. As we have worked to understand what participants learned from this MOOC, we have encountered methodological issues that likely impact a wide variety of research on MOOCs. Specifically, because many participants in our MOOC began but did not complete the course, analyzing data collected at the end of the course provides information about a potentially nonrepresentative sample of participants that likely does not generalize to the full group who started the course. After describing the generalizability issues that arose in our own research, we describe potential approaches for addressing these issues in MOOC research more broadly

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation

Background: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. Methods: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S’, fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. Results: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S’ (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87–0.99]|0.91[0.84–0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). Conclusion: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR

Two fish in a pod. Mislabelling on board threatens sustainability in mixed fisheries

Accuracy in reporting captures is a key element to achieve fisheries sustainability. However, identification of the catches might be a challenge when two or more species are morphologically similar and caught jointly, like the mixed fisheries of black hakes in East Atlantic African waters. Black hakes (Merluccius senegalensis and M. polli) are tough to differentiate without previous training due to their high morphological resemblance. The two species are managed as a single stock, although the biological differences between them suggest the need of a separate management. In this study, a total of 806 black hakes were visually identified by fishers on deck of fishing vessels operating in Mauritania and Senegal waters, then assigned to a species by sequencing 450bp of the Mitochondrial Control Region. Comparing the results with visual identification we found 31.4% of the total catch were incorrectly labelled on board by the fishermen. The accuracy of the fishers' identification depended on the depth of capture and on fish size, larger individuals caught from deeper waters being more correctly assigned to M. polli. Mislabelling biased to M. polli suggests that M. senegalensis, already catalogued as endangered, is being underreported, which could endanger the conservation of this species and threaten the sustainability of black hake fisheries. Our results highlight the need for separate evaluation of the stocks in mixed fisheries for morphologically similar fish. Thus, monitoring through DNA barcoding in the very first step of the seafood chain surveys would improve accurate species delimitation and reduce its impact on the correct assessment of the stocks.info:eu-repo/semantics/publishedVersio

Improving cardiovascular magnetic resonance access in low- and middle-income countries for cardiomyopathy assessment: rapid cardiovascular magnetic resonance

AIMS: To evaluate the impact of a simplified, rapid cardiovascular magnetic resonance (CMR) protocol embedded in care and supported by a partner education programme on the management of cardiomyopathy (CMP) in low- and middle-income countries (LMICs). METHODS AND RESULTS: Rapid CMR focused particularly on CMP was implemented in 11 centres, 7 cities, 5 countries, and 3 continents linked to training courses for local professionals. Patients were followed up for 24 months to assess impact. The rate of subsequent adoption was tracked. Five CMR conferences were delivered (920 attendees-potential referrers, radiographers, reporting cardiologists, or radiologists) and five new centres starting CMR. Six hundred and one patients were scanned. Cardiovascular magnetic resonance indications were 24% non-contrast T2* scans [myocardial iron overload (MIO)] and 72% suspected/known cardiomyopathies (including ischaemic and viability). Ninety-eighty per cent of studies were of diagnostic quality. The average scan time was 22 ± 6 min (contrast) and 12 ± 4 min (non-contrast), a potential cost/throughput reduction of between 30 and 60%. Cardiovascular magnetic resonance findings impacted management in 62%, including a new diagnosis in 22% and MIO detected in 30% of non-contrast scans. Nine centres continued using rapid CMR 2 years later (typically 1-2 days per week, 30 min slots). CONCLUSIONS: Rapid CMR of diagnostic quality can be delivered using available technology in LMICs. When embedded in care and a training programme, costs are lower, care is improved, and services can be sustained over time. KEY QUESTION: KEY FINDING: TAKE-HOME MESSAGE

The On-Site Analysis of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) observatory will be one of the largest ground-based very high-energy gamma-ray observatories. The On-Site Analysis will be the first CTA scientific analysis of data acquired from the array of telescopes, in both northern and southern sites. The On-Site Analysis will have two pipelines: the Level-A pipeline (also known as Real-Time Analysis, RTA) and the level-B one. The RTA performs data quality monitoring and must be able to issue automated alerts on variable and transient astrophysical sources within 30 seconds from the last acquired Cherenkov event that contributes to the alert, with a sensitivity not worse than the one achieved by the final pipeline by more than a factor of 3. The Level-B Analysis has a better sensitivity (not be worse than the final one by a factor of 2) and the results should be available within 10 hours from the acquisition of the data: for this reason this analysis could be performed at the end of an observation or next morning. The latency (in particular for the RTA) and the sensitivity requirements are challenging because of the large data rate, a few GByte/s. The remote connection to the CTA candidate site with a rather limited network bandwidth makes the issue of the exported data size extremely critical and prevents any kind of processing in real-time of the data outside the site of the telescopes. For these reasons the analysis will be performed on-site with infrastructures co-located with the telescopes, with limited electrical power availability and with a reduced possibility of human intervention. This means, for example, that the on-site hardware infrastructure should have low-power consumption. A substantial effort towards the optimization of high-throughput computing service is envisioned to provide hardware and software solutions with high-throughput, low-power consumption at a low-cost.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Physical Model Tests on Spar Buoy for Offshore Floating Wind Energy Conversion

ABSTRACT: The present paper describes the experiences gained from the design methodology and operation of a 3D physical modelexperiment aimed to investigate the dynamic behaviour of a spar buoy floating offshore wind turbine. The physical model consists in a Froude-scaled NREL 5MW reference wind turbine (RWT) supported on the OC3-Hywind floating platform. Experimental tests have been performed at Danish Hydraulic Institute (DHI) offshore wave basin within the European Union-Hydralab+ Initiative, in April 2019. The floating wind turbine model has been subjected to a combination of regular and irregular wave attacks and different wind loads. Measurements of displacements, rotations, accelerations, forces response of the floating model and at the mooring lines have been carried out. First, free decay tests have been analysed to obtain the natural frequency and the modal damping ratios of each degree of freedom governing the offshore. Then, the results concerning regular waves, with orthogonal incidence to the structure, are presented. The results show that most of longitudinal dynamic response occurs at the wave frequency and most of lateral dynamic response occurs at rigid-body frequencies.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654110, HYDRALAB+

Impact of COVID-19 Confinement on Physical Activity and Sedentary Behaviour in Spanish University Students: Role of Gender

[EN] During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain "ad hoc" questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.S

A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study

<p>Abstract</p> <p>Background</p> <p>An attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (<it>IGF-1R</it>).</p> <p>Methods</p> <p>In an elderly population from North-eastern Italy (<it>n </it>= 668 subjects, age range 70–106 years) we investigated the <it>IGF-1R </it>polymorphism G3174A (<it>rs2229765</it>) and the plasma concentration of free IGF-1. Frequency distributions were compared using χ²-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at α = 0.05.</p> <p>Results</p> <p>Males showed an age-related increase in the A-allele of <it>rs2229765 </it>and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between <it>rs2229765 </it>genotype and IGF-1 in the females.</p> <p>Conclusion</p> <p>These findings confirm the importance of the <it>rs2229765 </it>minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.</p

SCIPP: An Expanded Community of Practice - Community Publishing

SCIPP redefines and expands the existing notions about what makes for a vibrant and robust community of practice by partnering CSUSB students and professors with K-12 students, parents, and educators, along with committed community partners. SCIPP encourages curiosity in ways that leads to critical thinking, exploration, risk taking , confidence building, open-mindedness, and other personal traits that equip them with the softskills to be active, critical, and creative contributors to our communities. SCIPP pedagogy embraces our students\u27 collective wisdom and focuses on relational building where multi-directional communication is promoted and students are viewed as equal stakeholders in their own educations. SCIPP puts collaboration into action which in turn fosters community-based lifelong learning. SCIPP provides the open intellectual space for future university students (our K-12 students) to engage with existing university students in meaningful ways so as to sustain interconnected partnerships facilitating community engagement. It supports parents as experts in the education of their children and acknowledges parents as the first conduits to spark their children’s imagination while they actively participate in education enriching activities and programs. Everyone involved is committed to creating a secure and open atmosphere for dreaming, sharing, and learning. Together we explore the aspects of community publishing through collaborative learning in formal and informal settings relating to digital and printed medias