The Role of Negative and Positive Urgency in the Relationship Between Craving and Symptoms of Problematic Video Game Use

Spanish Research Agency (Agencia Española de Investigación),Spanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovación; MCIN/AEI/10.13039/501100011033/)PID2020- 116535 GB-I00.Grant (FPU21/00462, Ministerio de Ciencia e Innovación)Grant (PRE2018-085150, Ministerio de Ciencia, Innovación y Universidades

A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.Cancer Research UK FC0010048UK Medical Research Council FC0010048Wellcome Trust FC0010048Ministerio de Economía y Competitividad BFU2016-75058-PEuropean Research Council ERC2014 AdG669898 TARLOO

Response to sequential treatment schedules in childhood epilepsy Risk for development of refractory epilepsy

AbstractPurposeTo investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood.MethodsAll children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. “Seizure control” was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and “refractory epilepsy” as failure of >2 drugs plus >1 seizure/month for ≥18 months.Results343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving “seizure control” was 70% and 86% at 5 and 10 years. 59% of patients were “controlled” with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally “controlled” with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years.ConclusionAfter failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy

Sevoflurano como coadyuvante en la sedación durante ventilación mecánica en pacientes médicos de unidad de cuidados intensivos: resultados preliminares en una serie de casos

ResumenObjetivoExplicar nuestra experiencia preliminar en la utilización de sedación inhalatoria de manera estandarizada con sevoflurano mediante el dispositivo Anaesthetic Conserving Device en pacientes críticos intubados en nuestra unidad de cuidados intensivos (UCI).PacientesSe ha utilizado en 9 casos, en pacientes adultos (6 hombres y 3 mujeres), durante un periodo de 24meses.ResultadosSe ha conseguido una adecuada implantación del protocolo por parte de médicos y personal de enfermería, logrando los objetivos de sedación fijados en un primer momento (RASS 0, −2) y sin obtener resultados adversos ni efectos secundarios a nivel hepático y/o renal.ConclusionesEn nuestra limitada experiencia, la sedación inhalatoria con sevoflurano coadyuvante en UCI es una técnica segura y complementaria al uso de fármacos intravenosos, como propofol, remifentanilo y midazolam, utilizados habitualmente para lograr una sedación guiada por objetivos.AbstractObjectiveTo disclose our preliminary experience in inhalation sedation with sevoflorane in a standardized manner using the Anaesthetic Conserving Device in intubated, critically ill patients in our ICU.PatientsIt has been used in 9 cases of adult patients (6 men and 3 women) over 24 months.ResultsA proper implementation of the protocol by physicians and the nursing staff has been achieved, meeting the goals established for sedation (RASS 0, −2) free of hepatic or renal adverse outcomes or side effects.ConclusionsIn our limited experience, adjuvant inhalation sedation with sevoflorane in the ICU is safe and complementary to the use of intravenous drugs such as propofol, remifentanil and midazolam, which are currently commonly used to achieve goal-directed sedation

The Rad50 coiled-coil domain is indispensable for Mre11 complex functions

The Mre11 complex (Mre11, Rad50 and Xrs2 in Saccharomyces cerevisiae) influences diverse functions in the DNA damage response. The complex comprises the globular DNA-binding domain and the Rad50 hook domain, which are linked by a long and extended Rad50 coiled-coil domain. In this study, we constructed rad50 alleles encoding truncations of the coiled-coil domain to determine which Mre11 complex functions required the full length of the coils. These mutations abolished telomere maintenance and meiotic double-strand break (DSB) formation, and severely impaired homologous recombination, indicating a requirement for long-range action. Nonhomologous end joining, which is probably mediated by the globular domain of the Mre11 complex, was also severely impaired by alteration of the coiled-coil and hook domains, providing the first evidence of their influence on this process. These data show that functions of Mre11 complex are integrated by the coiled coils of Rad50.Swiss National Science Foundation and Eugen and Elisabeth Schellenberg Foundation GM56888, PBZH33-112756, PA0033-117484Ministerio de Ciencia e Innovación BFU2006-05260, 2010 CSD2007-01

Interdependence of the Rad50 hook and globular domain functions

Rad50 contains a conserved Zn2+ coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here we focused on rad50 mutations flanking the Zn2+-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end-joining, and DNA double strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled coil and globular ATPase domain, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions

Infant Gut Microbiota Associated with Fine Motor Skills

Background: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. Methods: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. Results: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. Conclusions: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.This study was granted by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341); Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-02) and partially funded by the European Commission MyNewGut FP7 EU Project (Grant agreement n° 613979). Research post-doctoral fellowship from the Alfonso Martín Escudero Foundation; MyNewGut FP7 EU Project (Grant agreement n° 613979); DynaHEALTH EU Project HORIZON 2020 (Grant agreement n°: 633595-2); Marie Curie post-doctoral fellowship (FP7, no. 329812, NutriOmics); The first author received Pre-Doc scholarships from the Spanish Ministry of Education, Culture and Sports (FPU16/04587). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Calculation of kinetic parameters βeff and Λ with modified open source Monte Carlo code OpenMC(TD)

This work presents the methodology used to expand the capabilities of the Monte Carlo code OpenMC for the calculation of reactor kinetic parameters: effective delayed neutron fraction βeff and neutron generation time Λ. The modified code, OpenMC(Time-Dependent) or OpenMC(TD), was then used to calculate the effective delayed neutron fraction by using the prompt method, while the neutron generation time was estimated using the pulsed method, fitting Λ to the decay of the neutron population. OpenMC(TD) is intended to serve as an alternative for the estimation of kinetic parameters when licensed codes are not available. The results obtained are compared to experimental data and MCNP calculated values for 18 benchmark configurations.Fil: Romero Barrientos, J.. Comision Chilena de Energia Nuclear; Chile. Universidad de Chile; ChileFil: Marquez Damian, Jose Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. European Spallation Source; SueciaFil: Molina, F.. Comision Chilena de Energia Nuclear; Chile. Universidad Andrés Bello; ChileFil: Zambra, M.. Comision Chilena de Energia Nuclear; Chile. Universidad Diego Portales; ChileFil: Aguilera, P.. Comision Chilena de Energia Nuclear; Chile. Universidad de Chile; ChileFil: López Usquiano, F.. Comision Chilena de Energia Nuclear; Chile. Universidad de Chile; ChileFil: Parra, B.. Instituto de Física Corpuscular; EspañaFil: Ruiz, A.. Comision Chilena de Energia Nuclear; Chile. Universidad de Chile; Chil

Increase in the erosion rate due to the impact of climate change on sea level rise: Victoria Beach, a case study

This article provides a general methodology for calculating the retreat of the coastline and the volume of sand necessary to renourish a beach due to sea level rise (SLR) in the medium-long term. An example is presented, Victoria Beach, and a projection is made for the years 2030, 2040, 2050, and 2100. The results obtained take into account global sea level rise (GSLR), which is worldwide, and local sea level rise (LSLR), which considers climate variability and vertical land movements. Regarding GSLR, data were provided by the projections from IPCC (Intergovernmental Panel on Climate Change) scenarios and empirical models, such as Rahmstorf and Pfeffer. The LSLR data came from the tide gauge station located in Cadiz. Finally, the results obtained showed that global warming impacts erosive effects and the subsequent volume of sand required to renourish beaches. The total sea level rise (TSLR) projections indicated for Victoria Beach are relatively higher than the GSLR projections. Even in the best IPCC scenario (RCP 2.6), Victoria Beach presents a significant erosion of 52 m, requiring a volume of sand of 1.0 Mm3 to supply renourishmentPostprint (published version