Oxidative Stress Induced by Excess of Adiposity Is Related to a Downregulation of Hepatic SIRT6 Expression in Obese Individuals

Sirt6 is a member of the sirtuin family involved in physiological and pathological processes including aging, cancer, obesity, diabetes, and energy metabolism. This study is aimed at evaluating the relationship between liver SIRT6 gene expression and the oxidative stress network depending on adiposity levels in Zucker rats, an animal model of metabolic syndrome. We observed that liver-specific SIRT6 expression is reduced in an in vivo model of spontaneous obesity and metabolic syndrome. We also observed that SIRT6 expression in the liver is positively associated with SIRT1 and GST-M2 expressions, two proteins involved in antioxidant protection pathways and inversely related to body weight and plasmatic oxidative status. Interestingly, the SIRT6 expression is upregulated after energy restriction-induced weight loss concomitantly with an improvement in oxidative stress markers. These results suggest that SIRT6 may be a potential therapeutic target for the treatment of obesity and associated metabolic disorders, such as liver disease.Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Instituto de Salud Carlos IIIEuropean Regional Development Fund (FEDER

Effort estimation of FLOSS projects: A study of the Linux kernel

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 SpringerEmpirical research on Free/Libre/Open Source Software (FLOSS) has shown that developers tend to cluster around two main roles: “core” contributors differ from “peripheral” developers in terms of a larger number of responsibilities and a higher productivity pattern. A further, cross-cutting characterization of developers could be achieved by associating developers with “time slots”, and different patterns of activity and effort could be associated to such slots. Such analysis, if replicated, could be used not only to compare different FLOSS communities, and to evaluate their stability and maturity, but also to determine within projects, how the effort is distributed in a given period, and to estimate future needs with respect to key points in the software life-cycle (e.g., major releases). This study analyses the activity patterns within the Linux kernel project, at first focusing on the overall distribution of effort and activity within weeks and days; then, dividing each day into three 8-hour time slots, and focusing on effort and activity around major releases. Such analyses have the objective of evaluating effort, productivity and types of activity globally and around major releases. They enable a comparison of these releases and patterns of effort and activities with traditional software products and processes, and in turn, the identification of company-driven projects (i.e., working mainly during office hours) among FLOSS endeavors. The results of this research show that, overall, the effort within the Linux kernel community is constant (albeit at different levels) throughout the week, signalling the need of updated estimation models, different from those used in traditional 9am–5pm, Monday to Friday commercial companies. It also becomes evident that the activity before a release is vastly different from after a release, and that the changes show an increase in code complexity in specific time slots (notably in the late night hours), which will later require additional maintenance efforts

Epigenetic Landscape in Blood Leukocytes Following Ketosis and Weight Loss Induced by a Very Low Calorie Ketogenic Diet (VLCKD) in Patients With Obesity

[Abstract] Background:The molecular mechanisms underlying the potential health benefits of a ketogenic diet areunknown and could be mediated by epigenetic mechanisms.Objective:To identify the changes in the obesity-related methylome that are mediated by the inducedweight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenicdiet (VLCKD).Methods:Twenty-one patients with obesity (n¼12 women, 47.9±1.02 yr, 33.0±0.2 kg/m2) after 6months on a VLCKD and 12 normal weight volunteers (n¼6 women, 50.3±6.2 yrs, 22.7±1.5 kg/m2)were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes wereobtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD(n¼10) and at baseline in volunteers (n¼12). Results were further validated by pyrosequencing inrepresentative cohort of patients on a VLCKD (n¼18) and correlated with gene expression.Results:After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes).The VLCKD altered methylation levels in patients with obesity had high resemblance with those fromnormal weight volunteers and was concomitant with a downregulation of DNA methyltransferases(DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein meta-bolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoringassociated events were identified, includingZNF331,FGFRL1(VLCKD-induced weight loss) andCBFA2T3,C3orf38,JSRP1, andLRFN4(VLCKD-induced ketosis). Interestingly,ZNF331andFGFRL1were validated inan independent cohort and inversely correlated with gene expression.Conclusions:The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive ofnormal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020)Xunta de Galicia; IN607B202

Epigenetic Landscape in Blood Leukocytes Following Ketosis and Weight Loss Induced by a Very Low Calorie Ketogenic Diet (VLCKD) in Patients with Obesity

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Methods: Twenty-one patients with obesity (n ¼ 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m2 ) after 6 months on a VLCKD and 12 normal weight volunteers (n ¼ 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m2 ) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n ¼ 10) and at baseline in volunteers (n ¼ 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n ¼ 18) and correlated with gene expression. Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020). The funding source had no involvement in the study design or interpretation of the result

New Mediterranean biodiversity records (March 2016)

In this Collective Article on “New Mediterranean Biodiversity Records”, we present additional records of species found in the Mediterranean Sea. These records refer to eight different countries mainly throughout the northern part of the basin, and include 28 species, belonging to five Phyla. The findings per country include the following species: Spain: Callinectes sapidus and Chelidonura fulvipunctata; Monaco: Aplysia dactylomela; Italy: Charybdis (Charybdis) feriata, Carcharodon carcharias, Seriola fasciata, and Siganus rivulatus; Malta: Pomacanthus asfur; Croatia: Lagocephalus sceleratus and Pomadasys incisus; Montenegro: Lagocephalus sceleratus; Greece: Amathia (Zoobotryon) verticillata, Atys macandrewii, Cerithium scabridum, Chama pacifica, Dendostrea cf. folium, Ergalatax junionae, Septifer cumingii, Syphonota geographica, Syrnola fasciata, Oxyu- richthys petersi, Scarus ghobban, Scorpaena maderensis, Solea aegyptiaca and Upeneus pori; Turkey: Lobotes surinamensis, Ruvettus pretiosus and Ophiocten abyssicolum. In the current article, the presence of Taractes rubescens (Jordan & Evermann, 1887) is recorded for the first time in the Mediterranean from Italy. The great contribution of citizen scientists in monitoring biodiversity records is reflected herein, as 10% of the authors are citizen scientists, and contributed 37.5% of the new findings.peer-reviewe

Active commuting to and from university, obesity and metabolic syndrome among Colombian university students

Background: There is limited evidence concerning how active commuting (AC) is associated with health benefits in young. The aim of the study was to analyze the relationship between AC to and from campus (walking) and obesity and metabolic syndrome (MetS) in a sample of Colombian university students. Methods: A total of 784 university students (78.6% women, mean age = 20.1 ± 2.6 years old) participated in the study. The exposure variable was categorized into AC (active walker to campus) and non-AC (non/infrequent active walker to campus: car, motorcycle, or bus) to and from the university on a typical day. MetS was defined in accordance with the updated harmonized criteria of the International Diabetes Federation criteria. Results: The overall prevalence of MetS was 8.7%, and it was higher in non-AC than AC to campus. The percentage of AC was 65.3%. The commuting distances in this AC from/to university were 83.1%, 13.4% and 3.5% for < 2 km, 2- 5 km and > 5 km, respectively. Multiple logistic regressions for predicting unhealthy profile showed that male walking commuters had a lower probability of having obesity [OR = 0.45 (CI 95% 0.25–0.93)], high blood pressure [OR = 0.26 (CI 95% 0.13–0.55)] and low HDL cholesterol [OR = 0.29 (CI 95% 0.14–0.59)] than did passive commuters. Conclusions: Our results suggest that in young adulthood, a key life-stage for the development of obesity and MetS, AC could be associated with and increasing of daily physical activity levels, thereby promoting better cardiometabolic health.This study was part of the project entitled “Body Adiposity Index and Biomarkers of Endothelial and Cardiovascular Health in Adults”, which was funded by Centre for Studies on Measurement of Physical Activity, School of Medicine and Health Sciences, Universidad del Rosario (Code N° FIUR DNBG001) and Universidad de Boyacá (Code N° RECT 60)

Towards Endometriosis Diagnosis by Gadofosveset-Trisodium Enhanced Magnetic Resonance Imaging

Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10–15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8–11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings

Multi-Centre, Multi-Vendor and Multi-Disease Cardiac Segmentation: The M&Ms Challenge

The emergence of deep learning has considerably advanced the state-of-the-art in cardiac magnetic resonance (CMR) segmentation. Many techniques have been proposed over the last few years, bringing the accuracy of automated segmentation close to human performance. However, these models have been all too often trained and validated using cardiac imaging samples from single clinical centres or homogeneous imaging protocols. This has prevented the development and validation of models that are generalizable across different clinical centres, imaging conditions or scanner vendors. To promote further research and scientific benchmarking in the field of generalizable deep learning for cardiac segmentation, this paper presents the results of the Multi-Centre, Multi-Vendor and Multi-Disease Cardiac Segmentation (M&Ms) Challenge, which was recently organized as part of the MICCAI 2020 Conference. A total of 14 teams submitted different solutions to the problem, combining various baseline models, data augmentation strategies, and domain adaptation techniques. The obtained results indicate the importance of intensity-driven data augmentation, as well as the need for further research to improve generalizability towards unseen scanner vendors or new imaging protocols. Furthermore, we present a new resource of 375 heterogeneous CMR datasets acquired by using four different scanner vendors in six hospitals and three different countries (Spain, Canada and Germany), which we provide as open-access for the community to enable future research in the field

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior