Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley

Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions), comprising of 95 photoperiod-sensitive (Ppd-H1) and 123 accessions with reduced photoperiod sensitivity (ppd-H1) to long-day (LD) through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH) conditions (LD; 16/8 h; ∼20/∼16°C day/night). Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs) chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS). GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1) and BFL (BARLEY FLORICAULA/LEAFY) genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley

Proceso de Bolonia (VI): aprendiendo comunicación para la salud en el Grado de Medicina

La comunicación forma parte de la actividad clínica y en ocasiones determina el éxito o fracaso del proceso asistencial. Sin embargo, no ha sido reconocida en los planes de estudio del Estado español hasta muy recientemente, sobre todo con el impulso del llamado 'Plan Bolonia'. En el año 2009 se aprobó en la Facultad de Medicina de la Universitat de Barcelona un nuevo plan docente que proponía incorporar la enseñanza de la comunicación en las materias clínicas y pre-clínicas, contabilizando entre 3 y 6 créditos europeos (ECTS), como competencia transversal. El presente artículo aborda el diseño de esta competencia, los pros y contras, cómo se inserta en diferentes asignaturas y cómo puede evaluarse

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

The development of clinica lpractice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance withr regard to adverse drug reactions.The poten-tial of pharmacogenomicbiomarkers has been extensively investigated in recent years.However,several barriers to implementing the use of pharmacogenomics testing exist.We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of majorgene/drug pairs.Of 11 potential barriers,the highest importance was attributed to lack of institutional support for pharmacogenomic stesting,and to the issues related to the lack of guidelines.Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen.In this perspective article,we compare the relative importance of 29 gene/drugpairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutic sstudy,and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testingThe work in the author’s laboratory is financed by Grants PS09/00943, PS09/00469, RETICS RIRAAF RD07/0064/0016, and CIBERehd from Instituto de Salud CarlosIII,Madrid, Spain, and by Grants GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Unio

Prolonged Sitting Time: Barriers, Facilitators and Views on Change among Primary Healthcare Patients Who Are Overweight or Moderately Obese

Background and Objectives Prolonged sitting time has negative consequences on health, although the population is not well aware of these harmful effects. We explored opinions expressed by primary care patients diagnosed as overweight or moderately obese concerning their time spent sitting, willingness to change, and barriers, facilitators, goals and expectations related to limiting this behaviour. Methods A descriptive-interpretive qualitative study was carried out at three healthcare centres in Barcelona, Spain, and included 23 patients with overweight or moderate obesity, aged 25 to 65 years, who reported sitting for at least 6 hours a day. Exclusion criteria were inability to sit down or stand up from a chair without help and language barriers that precluded interview participation. Ten in-depth, semi-structured interviews (5 group, 5 individual) were audio recorded from January to July 2012 and transcribed. The interview script included questions about time spent sitting, willingness to change, barriers and facilitators, and the prospect of assistance from primary healthcare professionals. An analysis of thematic content was made using ATLAS.Ti and triangulation of analysts. Results The most frequent sedentary activities were computer use, watching television, and motorized journeys. There was a lack of awareness of the amount of time spent sitting and its negative consequences on health. Barriers to reducing sedentary time included work and family routines, lack of time and willpower, age and sociocultural limitations. Facilitators identified were sociocultural change, free time and active work, and family surroundings. Participants recognized the abilities of health professionals to provide help and advice, and reported a preference for patient-centred or group interventions. Conclusions Findings from this study have implications for reducing sedentary behaviour. Patient insights were used to design an intervention to reduce sitting time within the frame of the SEDESTACTIV clinical trial

Singularity-invariant leg rearrangements in Stewart-Gough platforms

Postprint (author’s final draft

Effectiveness of a primary care-based intervention to reduce sitting time in overweight and obese patients (SEDESTACTIV): a randomized controlled trial; rationale and study design

Background: There is growing evidence suggesting that prolonged sitting has negative effects on people's weight, chronic diseases and mortality. Interventions to reduce sedentary time can be an effective strategy to increase daily energy expenditure. The purpose of this study is to evaluate the effectiveness of a six-month primary care intervention to reduce daily of sitting time in overweight and mild obese sedentary patients. Method/Design: The study is a randomized controlled trial (RCT). Professionals from thirteen primary health care centers (PHC) will randomly invite to participate mild obese or overweight patients of both gender, aged between 25 and 65 years old, who spend 6 hours at least daily sitting. A total of 232 subjects will be randomly allocated to an intervention (IG) and control group (CG) (116 individuals each group). In addition, 50 subjects with fibromyalgia will be included. Primary outcome is: (1) sitting time using the activPAL device and the Marshall questionnaire. The following parameters will be also assessed: (2) sitting time in work place (Occupational Sitting and Physical Activity Questionnaire), (3) health-related quality of life (EQ-5D), (4) evolution of stage of change (Prochaska and DiClemente's Stages of Change Model), (5) physical inactivity (catalan version of Brief Physical Activity Assessment Tool), (6) number of steps walked (pedometer and activPAL), (7) control based on analysis (triglycerides, total cholesterol, HDL, LDL, glycemia and, glycated haemoglobin in diabetic patients) and (8) blood pressure and anthropometric variables. All parameters will be assessed pre and post intervention and there will be a follow up three, six and twelve months after the intervention. A descriptive analysis of all variables and a multivariate analysis to assess differences among groups will be undertaken. Multivariate analysis will be carried out to assess time changes of dependent variables. All the analysis will be done under the intention to treat principle. Discussion: If the SEDESTACTIV intervention shows its effectiveness in reducing sitting time, health professionals would have a low-cost intervention tool for sedentary overweight and obese patients management

Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice guidelines and Quality Certification Do Not Avert Variability in Clinical Practice

Background: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. Methods: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. Results: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. Conclusions: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process

Origin and Control of Chemoselectivity in Cytochrome c Catalyzed Carbene Transfer into Si–H and N–H bonds

A cytochrome c heme protein was recently engineered to catalyze the formation of carbon–silicon bonds via carbene insertion into Si–H bonds, a reaction that was not previously known to be catalyzed by a protein. High chemoselectivity toward C–Si bond formation over competing C–N bond formation was achieved, although this trait was not screened for during directed evolution. Using computational and experimental tools, we now establish that activity and chemoselectivity are modulated by conformational dynamics of a protein loop that covers the substrate access to the iron–carbene active species. Mutagenesis of residues computationally predicted to control the loop conformation altered the protein’s chemoselectivity from preferred silylation to preferred amination of a substrate containing both N–H and Si–H functionalities. We demonstrate that information on protein structure and conformational dynamics, combined with knowledge of mechanism, leads to understanding of how non-natural and selective chemical transformations can be introduced into the biological world

Vanadium Substitution Dictates H Atom Uptake at Lindqvist-type Polyoxotungstates

Understanding how modification of molecular structures changes the thermochemistry of H atom uptake can provide design criteria for the formation of highly active catalysts for reductive transformations. Herein, we describe the effect of doping an atomically precise polyoxotungstate with vanadium on proton-coupled electron transfer (PCET) reactivity. The Lindqvist-type polyoxotungstate [W6O19]2–displays reversible redox chemistry, which was found to be unchanged in the presence of acid, indicating an inability to couple reduction with protonation. However, the incorporation of a single vanadium center into the structure significantly changes the reactivity, and the potential required for one-electron reduction of [VW5O19]3– was shown to vary with the strength of the acid added. Construction of a potential-pKadiagram allowed assessment of the thermodynamics of H atom uptake, indicating BDFE(O–H) ≈ 64 kcal/mol, while chemical synthesis of the reduced/protonated derivative (TBA)3[VW5O19H] was used to probe the position of protonation. tures changes the thermochemistry of H atom uptake can providedesign criteria for the formation of highly active catalysts for reductivetransformations. Herein, we describe the effect of doping anatomically precise polyoxotungstate with vanadium on proton-coupledelectron transfer (PCET) reactivity. The Lindqvist-type polyoxotung-state [W6O19]2− displays reversible redox chemistry, which was foundto be unchanged in the presence of acid, indicating an inability tocouple reduction with protonation. However, the incorporation of asingle vanadium center into the structure significantly changes thereactivity, and the potential required for one-electron reduction of[VW5O19]3− was shown to vary with the strength of the acid added.Construction of a potential-pUnderstanding how modification of molecular struc-tures changes the thermochemistry of H atom uptake can providedesign criteria for the formation of highly active catalysts for reductivetransformations. Herein, we describe the effect of doping anatomically precise polyoxotungstate with vanadium on proton-coupledelectron transfer (PCET) reactivity. The Lindqvist-type polyoxotung-state [W6O19]2− displays reversible redox chemistry, which was foundto be unchanged in the presence of acid, indicating an inability tocouple reduction with protonation. However, the incorporation of asingle vanadium center into the structure significantly changes thereactivity, and the potential required for one-electron reduction of[VW5O19]3− was shown o vary with the strength of the acid added.Construction of a potential-pKa diagram allowed assessment of thethermodynamics of H atom uptake, indicating BDFE(O−H) ≈ 64 kcal/mol, while chemical synthesis of the reduced/protonatedderivative (TBA)3[VW5O19H] was used to probe the position of protoKa diagram allowed assessment of thethermodynamics of H atom uptake, indicating BDFE(O−H) ≈ 64 kcal/mol, while chemical synthesis of the reduced/protonatedderivative (TBA)3[VW5O19H] was used to probe the position of protonation

Structural basis for the human SENP5's SUMO isoform discrimination

Altres ajuts: ICREA AcademiaPost-translational SUMO modification is a widespread mechanism for regulating protein function within cells. In humans, SUMO-conjugated proteins are partially regulated by the deconjugating activity of six SENP family members. The proteolytic activity of these enzymes resides within a conserved catalytic domain that exhibits specificity for the two primary SUMO isoforms: SUMO1 and SUMO2/3. SENP5, along with SENP3, are nucleolar proteins involved in ribosome biogenesis and preferentially target SUMO2/3 isoforms. Here, we present the crystal structures of human SENP5 in complex with both SUMO1 and SUMO2 isoforms. These structures reveal a minimal complex interface and elucidate the molecular basis for SENP5's preference for the SUMO2 isoform. This preference can be attributed to a basic patch surrounding SENP5 Arg624 at the interface. Swapping mutagenesis and structural analysis demonstrate that Arg624 is favorably oriented to interact with Asp63 in SUMO2/3, while its interaction with the equivalent Glu67 in SUMO1 is less favorable. These results suggest that subtle structural differences within SUMO isoforms can significantly influence their deconjugation by SENP enzymes, opening new avenues for exploring the regulation of SUMOylation in various cellular processes and for developing therapeutic agents targeting SUMOylation pathways