Genetic control of purothionins in wheat: problems of the aneuploid analysis when searching for regulatory genes

The study of the genetic control of purothionins in wheat endosperm illustrates some of the problems and pitfalls faced in aneuploid analysis of regulatory effects. Biochemical and genetic evidence is presented indicating that the possible regulatory effect of genes located in group 5 chromosomes on the expression of the purothionin structural genes located in group 1 chromosomes is not actually operating "in vivo"

sta-1 is repressed by mir-58 family in Caenorhabditis elegans.

The miR-58 family comprises 6 microRNAs with largely shared functions, and with an overall high expression, because one of its members, miR-58, is the most abundant microRNA in Caenorhabditis elegans. We recently found that 2 TGF-β signaling pathways, Sma/Mab and Dauer, responsible for body size and dauer formation respectively, among other phenotypes, are downregulated by the miR-58 family. Here, we further explore this family by showing that it also acts through the sta-1 3'UTR. sta-1 encodes a transcription factor, homologous to mammalian STATs, that inhibits dauer formation in association with the TGF-β Dauer pathway. We also observe that mutants with a constitutively active TGF-β Dauer pathway express higher levels of sta-1 mRNA. Our results reinforce the view of the miR-58 family and STA-1 as regulators of dauer formation in coordination with the TGF-β Dauer pathway.This work was funded by Fondo de Investigaciones Sanitarias (PI08/642 and PI11/120 to E.L.). E.L., M.P.L. and A.G.S. were supported by programs Ramón y Cajal, Formación de Profesorado Universitario and Fondo de Investigaciones Sanitarias, respectively, all of them from the Spanish Government. C. elegans strains were provided by CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).S

Desarrollo de materiales online de apoyo para la realización del Trabajo de Fin de Grado

Depto. de Trabajo Social y Servicios SocialesFac. de Trabajo SocialFALSEsubmitte

Nothobranchius as a model for aging studies. A review

In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging

Actions and attitudes on the immunized patients against SARS-CoV-2.

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in outpatient care and in the case of exploratory procedures that do not require hospitalization.post-print156 K

La familia de mir-58 y el correceptor SMA-10 como moduladores de la señalización por TGFβ en Caenorhabditis elegans

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 17-07-2015La señalización celular controlada por la superfamilia de “Transforming Growth Factor β” (TGFβ) tiene un papel clave tanto en el desarrollo embrionario como en la homeostasis celular de los tejidos adultos. Aunque el funcionamiento básico de las rutas de TGFβ es conocido, no lo es tanto su modulación, por ejemplo por parte de los microRNAs o de diversos correceptores de membrana plasmática. Debido al protagonismo de las rutas de TGFβ en numerosos procesos biológicos y patológicos, la investigación sobre los moduladores de TGFβ comprende un campo importante, tanto desde un punto de vista biológico como biomédico. Como la señalización por TGFβ está relativamente conservada evolutivamente, hemos elegido el nematodo Caenorhabditis elegans como modelo experimental. En C. elegans existen dos rutas de TGFβ conocidas: TGFβ Sma/Mab, implicada en la adquisición del tamaño corporal, entre otros procesos; y TGFβ Dauer, que regula la entrada en el estadio de resistencia conocido como dauer. Hemos encontrado dos nuevos reguladores de la señalización de TGFβ: la familia de microRNAs de mir-58 y el correceptor SMA-10. En cuanto a la familia de mir-58, el mutante disponible para cuatro de los cinco miembros de esta familia de microRNAs es pequeño e incapaz de formar dauers. Nuestros resultados indican que la familia de mir-58 inhibe, mediante su unión a los 3’UTRs, la expresión de los mRNAs de dbl-1, sma-6, daf-4 y daf-1, todos ellos miembros clave y reguladores positivos, de las rutas TGFβ Sma/Mab y/o TGFβ Dauer. Hemos comprobado que, consistentemente con lo anterior, ambas rutas están sobreexpresadas en el mutante de la familia de mir-58. Experimentos epistáticos sugieren que la incapacidad de producir dauers de dicho mutante es debida a la sobreexpresión de TGFβ Dauer. En cambio, aunque la familia de mir-58 inhibe el crecimiento a través de TGFβ Sma/Mab, estos microRNAs tienen un efecto predominantemente promotor del tamaño corporal de forma independiente a TGFβ Sma/Mab. Asimismo, por lo que respecta a la regulación de la familia de mir-58, hemos observado que la expresión de dos de sus miembros, mir-58 y mir-80, está, a su vez, positivamente controlada por TGFβ Sma/Mab, creando así un bucle regulatorio negativo entre estos microRNAs y TGFβ Sma/Mab. También hemos encontrado que la proteína transmembrana SMA-10 participa de la ruta TGFβ Sma/Mab como regulador positivo del tamaño corporal de C. elegans, aunque este resultado ha sido publicado de forma independiente durante el transcurso de esta tesis. Nuestro trabajo muestra que SMA-10 es un componente dispensable en la señalización por TGFβ Sma/Mab: mientras que regula algunos fenotipos de la ruta como el tamaño corporal o el periodo reproductivo, no afecta a otros fenotipos regulados por TGFβ Sma/Mab, como la longevidad o inmunidad. Finalmente, hemos descubierto que SMA-10 tiene un papel inmunoprotector, dependiente de la ruta de Insulina, actuando corriente arriba de su único receptor en nematodos, DAF-2Transforming Growth Factor β (TGFβ) comprises a family of protein ligands involved in a wide range of animal processes, which play a key role in development and cellular homeostasis. Although the basic elements of the TGFβ signaling pathway are well known, there are also many side regulators, such as microRNAs and transmembrane coreceptors, which need to be investigated. Since TGFβ signaling is key to so many biological and pathological processes, it is important to study in detail those regulators. Given the relative evolutionary conservation of TGFβ pathways, we have tried to discover new TGFβ regulators using the model organism Caenorhabditis elegans. Two TGFβ pathways are known in C. elegans: TGFβ Sma/Mab, involved in many phenotypes such as body size, and TGFβ Dauer, which controls the decision to enter an alternative larval stage known as dauer, designed to resist harsh environmental conditions. We have found two new TGFβ regulators, the microRNA family mir-58 and the transmembrane protein SMA-10. It is known that a mir-58 family mutant, which lacks four of its five members, is small and dauer defective. Our results show that mir-58 family inhibits the expression of dbl-1, sma-6, daf-4 and daf-1 mRNAs through their 3’UTRs. All these mRNAs are key members, and positive regulators, of TGFβ Sma/Mab and/or TGFβ Dauer. In agreement, we have found that both TGFβ pathways are upregulated in the mir-58 family mutant. Our epistatic analyses suggest that the dauer defectiveness of the mir-58 family mutant is caused by an overexpression of TGFβ Dauer. In contrast, the small size of the mir-58 family mutant is unrelated to TGFβ Sma/Mab. We have discovered that, independently of the overall positive role on body size, mir-58 family also shows an additional inhibitory role on growth, which depends on its interaction with TGFβ Sma/Mab. Moreover, in relation to mir-58 family regulation, we show that TGFβ Sma/Mab, in turn, positively controls the expression of two members of this family, mir-58 and mir-80. Therefore a negative feedback loop is present between those microRNAs and TGFβ Sma/Mab. We also found that the transmembrane protein SMA-10 is a positive regulator of C. elegans body size, although this result was published after we discovered it independently. Our research shows that SMA-10 is not an obligated member of the TGFβ Sma/Mab signaling: while this coreceptor participates of some of the phenotypes controlled by that pathway, i.e. body size and reproductive span, it does not of other TGFβ Sma/Mab functions, i.e. longevity and immunity. Additionally, we show that SMA-10 plays a new role in immunity, dependent on the insulin pathway and upstream of the insulin receptor DAF-

SMA-10 Is a Non-Canonical Member of the TGF-β Sma/Mab Pathway and Immunity Regulator via the DAF-2 Insulin Receptor in Caenorhabditis elegans.

Transforming growth factor β (TGF-β) signalling pathways are highly conserved across metazoa and play essential roles not only during development but also in adult tissue maintenance. Alterations of these pathways usually result in a plethora of pathologies. In the nematode Caenorhabditis elegans, the TGF-β Sma/Mab (small/male abnormal) pathway regulates various worm phenotypes such as body size, immune response, ageing, matricide and reproductive span. SMA-10 has been described as a positive modulator of worm body size through the TGF-β Sma/Mab pathway. To better understand if SMA-10 is a core component of the pathway, we use gene epistatic analysis to assess the contribution of SMA-10 to various phenotypes regulated by TGF-β Sma/Mab. We confirm that SMA-10 controls body size and find that it also affects the matricide and reproductive span of the nematodes. However, neither male tail formation (previously reported) nor ageing appeared altered. Lastly, although null sma-10 worms are more susceptible to Pseudomonas aeruginosa infections than wild-types, this response does not depend on TGF-β Sma/Mab but on the insulin receptor DAF-2. We also show that the expression of sma-10 in either hypodermis or intestine fully rescues the wild-type immune response. Our results contribute to understanding the role of SMA-10 as a context-dependent component of TGF-β Sma/Mab, and reveal a function of SMA-10 in immunity in association to the Insulin/insulin-like growth factor signalling (IIS) pathway.This research was funded by Fondo de Investigaciones Sanitarias (FIS), grant numbers PI08/642 and PI11/120 to E.L., M.P.d.L., A.G.S. and E.L. were supported by programs Formación de Profesorado Universitario, FIS PI08/642 and Ramón y Cajal, respectively, all of them from the Spanish Government.S

Health-related quality of life in outpatients with COPD in daily practice: the VICE Spanish study

Antonio Martín1, José M Rodríguez-González Moro2, José L Izquierdo3, Elena Gobartt4, Pilar de Lucas2, The VICE Study Group1Medical Department, Pfizer, Madrid, Spain; 2Service of Pneumology, HGU Gregorio Marañón, Madrid, Spain; 3Service of Pneumology, Hospital General Universitario de Guadalajara, Guadalajara, Spain; 4Respiratory Area, Medical Department, Boehringer Ingelheim España, Madrid, SpainBackground: The objective of this study was to measure health-related quality of life (HRQL) in outpatients with chronic obstructive pulmonary disease (COPD) and to assess differences in HRQL according to age, gender, and severity of COPD.Methods: A total of 9405 patients (79% men, mean age 68 years) participated in a cross-sectional study. HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12). Severity of COPD was graded into three levels according to forced expiratory volume in one second value.Results: COPD severity was mild in 33.8% of cases, moderate in 49.3% and severe in 16.8%. The mean physical component summary (PCS-12) and mental component summary (MCS-12) scores were 36.8 ± 10.4 and 47.2 ± 11.2, respectively. General health and physical functioning domains were those with the lowest scores. The mean MCS-12 scores were significantly higher in men (47.9 ± 10.9) than in women (44.1 ± 11.8) (P < 0.001). Patients older than 60 years rated HRQL worse than patients aged 40–59 years. There were statistically significant differences according to severity of disease in the mean scores of all domains of the PCS-12 and MCS-12 scales.Conclusions: The present findings show the influence of female gender, older age and moderate-to-severe of airflow limitation on HRQL in outpatients with COPD attended in daily practice.Keywords: health status, health surveys, multicenter study, pulmonary disease, chronic obstructive/epidemiology, quality of life, questionnaire