A novel role for proline- and acid-rich basic region leucine zipper (PAR bZIP) proteins in the transcriptional regulation of a BH3-only proapoptotic gene.

Proline- and acid-rich (PAR) basic region leucine zipper (bZIP) proteins thyrotroph embryonic factor (TEF), D-site-binding protein (DBP), and hepatic leukemia factor have been involved in neurotransmitter homeostasis and amino acid metabolism. Here we demonstrate a novel role for these proteins in the transcriptional control of a BH3-only gene. PAR bZIP proteins are able to transactivate the promoter of bcl-gS. This promoter is particularly responsive to TEF activation and is silenced by NFIL3, a repressor that shares the consensus binding site with PAR bZIP proteins. Consistently, transfection of TEF induces the expression of endogenous bcl-gS in cancer cells, and this induction is independent of p53. A naturally occurring variant of DBP (tDBP), lacking the transactivation domain, has been identified and shown to impede the formation of active TEF dimers in a competitive manner and to reduce the TEF-dependent induction of bcl-gS. Of note, treatment of cancer cells with etoposide induces TEF activation and promotes the expression of bcl-gS. Furthermore, blockade of bcl-gS or TEF expression by a small interfering RNA strategy or transfection with tDBP significantly reduces the etoposide-mediated apoptotic cell death. These findings represent the first described role for PAR bZIP proteins in the regulation of a gene involved in the execution of apoptosis

Barbie eta superman: beste aukerarik ote? Artearen hezkuntza eta gorputz hezkuntzaren bidezko diziplinartekotasuna haurren pentsamendu kritikoa sustatzeko

Diziplinartekotasunak hainbat abantaila izan ditzake Lehen Hezkuntzan, horien artean kontzeptu teoriko eta metodologia praktikoen artean loturak ezartzea, edota eguneroko arazoei aurre egiteko ikuspuntu eta baliabide desberdinak garatzeko aukera ematea. Planteamendu horretatik abiatuta kasu azterketa bat egiten da bi helburuekin, alde batetik 6. mailako ikasleriak dituen gorputz osasuntsuari buruzko aurreiritziak identifikatzea, eta bestetik gai horri buruzko ezagutzak garatzeko Gorputz Hezkuntza eta Artearen Hezkuntzaren bidezko proiektu baten eraginkortasuna ebaluatzea. Emaitzak erakusten dutenez, parte-hartzaileen osasunari eta gorputz irudiari buruzko aurreiritziak zuzenki erlazionatuta daude ikusizko kulturan kontsumitzen dituzten estereotipoekin. Horretaz gain, ondorioztatu da Artearen Hezkuntza eta Gorputz Hezkuntzaren arteko elkarlanak ikasleen adierazpen gaitasunak sustatzen dituela, osagarriak diren hiru komunikazio-bide eskaintzen baititu: hitzen bidezkoa, gorputz adierazpena eta ikusizko lengoaia. Gainera, metodologia praktiko, motibatzaile eta erakargarrien bidez parte-hartzaileek eduki eta eredu berriak barneratzea lortzen dute, baita beraien aurreiritziaz hausnartzea eta estereotipatutako irudiei buruzko pentsamendu kritikoa garatzea ere, gorputz aniztasunarekiko begirunea suspertuz.; Interdisciplinary work in primary education offers a number of advantages, such as the opportunity to establish links between theoretical concepts and practical methods, or to develop different points of view and strategies to deal with everyday problems. Based on this approach, we analyse a case study for two purposes: on the one hand, to identify existing preconceptions about healthy bodies in the minds of 6th grade students, and on the other, to evaluate the results of a project in which the areas of Physical Education and Art Education collaborate to increase students’ knowledge on this issue. The results show that participants have preconceptions about health and body image that are directly related to the stereotypes they consume through visual culture. We also observed that the interaction between the areas of Art Education and Physical Education promotes pupils’ ability to express themselves by offering them three complementary means of communication: verbal language, body language, and visual language. In addition, through practical, motivating, and engaging methods, participants are able to internalise new concepts and role models, reflect on their preconceptions, and finally develop critical thinking skills in relation to stereotypical images and build respect for body diversity

Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells

AbstractBH3-only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy-induced expression of bik is independent of p53. Consistent with its pro-apoptotic activity, blockade of bik expression reduces the adriamycin-mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway. In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents

Knowledge, attitude, and patient advice on sustainable diets among Spanish health professionals

Current dietary patterns, especially in high-income countries, are unsustainable. Health professionals, due to their credibility and close contact with the general population, could serve as agents of change for the adoption of sustainable diets. The objective of this study was to assess the knowledge and attitude regarding sustainable diets among the health professionals in Spain. A 24-item online questionnaire was designed for this purpose, and sent to health professionals (i.e., dietitians-nutritionists, nurses, physicians, and pharmacists). From September 2021 to May 2022, 2,545 health professionals answered the survey completely. One-fifth of them had never heard the term “sustainable diet”, and most of them recognized having limited knowledge about it. They considered promoting sustainable diets when making dietary recommendations important, and pointed out that they would like to be trained on the topic. Indeed, they reported that all health professionals, independent of their career background, should be educated on sustainable diets. Efforts should be stressed on implementing training courses, at university level but also as continuous post-graduate training, providing health professionals in Spain the necessary knowledge to promote the adoption of sustainable diets among the population

Los primeros 1000 días: Una oportunidad para reducir la carga de las enfermedades no transmisibles

Growth and development are determined by genetic and environmental factors since the very early embryonic life. Long-term health risks, as obesity and other non-communicable diseases (NCD), could be programmed since these early stages. Early life, characterized by plasticity, is the ideal time to intervene and to prevent the risk of suffering a NCD (window of opportunity). Optimal nutrition during the first 1,000 days, since conception to the end of the second year of life, has a determinant role for long-term health. Pregnancy, infancy and toddler periods have specific nutritional requirements. Intestinal microbiota enhances maturation and functioning of the immune system. The interactions between host and intestinal microbiota are potential factors influencing early programming of the intestinal function. Alterations in intestinal colonization are associated to a higher risk of allergic diseases in childhood. Scientific evidence supports the fact that the first 1,000 days are crucial to achieve a better long-term health and represents a strategic period to intervene under the perspective of prevention and public health.El crecimiento y desarrollo de un individuo está determinado desde la etapa embrionaria por su genética y los factores ambientales con los que interactúa. Los riesgos para la salud infantil y adulta pueden programarse durante las etapas fetal-neonatal y esta programación metabólica precoz puede afectar al desarrollo posterior de enfermedades como la obesidad y otras enfermedades no transmisibles (ENT) asociadas. La vida temprana, por la gran plasticidad que la caracteriza, constituye el momento ideal para intervenir y prevenir el riesgo de ENT (ventana de oportunidad). Una nutrición óptima durante los primeros 1000 días, que comprende desde la concepción hasta los dos años, es clave para la salud a lo largo de la vida. El rápido crecimiento y desarrollo del organismo y sus funciones durante el embarazo, la lactancia y el niño de corta edad conlleva requisitos nutricionales específi cos en cada una de estas etapas. La microbiota del tracto gastrointestinal desempeña una labor fundamental en la función y el desarrollo del sistema inmune. Las interacciones entre el hospedador y su microbiota intestinal se consideran factores potenciales en la programación temprana de las funciones intestinales, con una evidencia creciente de que las alteraciones de la colonización bacteriana en el neonato se asocian con un mayor riesgo de enfermedad, incluidas las enfermedades alérgicas. La evidencia científi ca acumulada muestra que los primeros 1000 días son cruciales para alcanzar el mejor desarrollo y salud a largo plazo, y constituyen un periodo estratégico en términos de prevención y salud públicaEsta publicación ha sido promovida y financiada por el Instituto Danon

Bone mineral density, body composition, and metabolic health of very low birth weight infants fed in hospital following current macronutrient recommendations during the first 3 years of life

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.This research was partially funded by the ‘Fondo de Investigación Sanitaria’ (grant number PI041631

Preterm infants with necrotising enterocolitis demonstrate an unbalanced gut microbiota

©2017 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd Aim: This Lebanese study tested the hypothesis that differences would exist in the gut microbiota of preterm infants with and without necrotising enterocolitis (NEC), as reported in Western countries. Methods: This study compared 11 infants with NEC and 11 controls, all born at 27-35 weeks, in three neonatal intensive care units between January 2013 and March 2015. Faecal samples were collected at key time points, and microbiota was analysed by culture, quantitative PCR (qPCR) and temperature temporal gel electrophoresis (TTGE). Results: The cultures revealed that all preterm infants were poorly colonised and harboured no more than seven species. Prior to NEC diagnosis, significant differences were observed by qPCR with a higher colonisation by staphylococci (p = 0.034) and lower colonisations by enterococci (p = 0.039) and lactobacilli (p = 0.048) in the NEC group compared to the healthy controls. Throughout the study, virtually all of the infants were colonised by Enterobacteriaceae at high levels. TTGE analysis revealed no particular clusterisation, showing high interindividual variability. Conclusion: The NEC infants were poorly colonised with no more than seven species, and the controls had a more diversified and balanced gut microbiota. Understanding NEC aetiology better could lead to more effective prophylactic interventions and a reduced incidence

Induction of Nod2 in Myelomonocytic and Intestinal Epithelial Cells via Nuclear Factor-kB Activation

Nod2, a member of the Apaf1/Nod protein family, confers responsiveness to bacterial products and activates NF-kB, a ranscription factor that plays a central role in innate immunity. Recently, genetic variation in Nod2 has been associated with susceptibility to Crohn’s disease. Here, we report that expression of Nod2 is induced upon differentiation of CD34+ hematopoietic progenitor cells into granulocyte or monocyte/macrophages. In peripheral blood cells, the highest levels of Nod2 were observed in CD14+ (monocytes), CD15+ (granulocytes), and CD40+/CD86+ (dendritic cells) cell populations. Notably, stimulation of myeloblastic and epithelial cells with bacterial lipopolysaccharide or TNF resulted in up-regulation of Nod2. A search for consensus sites within the Nod2 promoter revealed a NF-kB binding element that was required for transcriptional activity in response to TNF . Moreover, ectopic expression of p65 induced transactivation, whereas that of dominant-negative I B blocked the transcriptional activity of the Nod2 promoter. Upon stimulation with TNF or lipopolysaccharide, both p50 and p65 subunits of NF-kB were bound to the Nod2 promoter. Thus, Nod2 expression is enhanced by proinflammatory cytokines and bacterial components via NF-kB, a mechanism that may contribute to the amplification of the innate immune response and susceptibility to inflammatory disease

Cell wall modifications that alter the exolytic activity of lactococcal phage endolysins have little impact on phage growth

Bacteriophages are a nuisance in the production of fermented dairy products driven by starter bacteria and strategies to reduce the risk of phage infection are permanently sought. Bearing in mind that the bacterial cell wall plays a pivotal role in host recognition and lysis, our goal was to elucidate to which extent modifications in the cell wall may alter endolysin activity and influence the outcome of phage infection in Lactococcus. Three lactococcal endolysins with distinct catalytic domains (CHAP, amidase and lysozyme) from phages 1,358, p2 and c2 respectively, were purified and their exolytic activity was tested against lactococcal mutants either overexpressing or lacking genes involved in the cell envelope stress (CES) response or in modifying peptidoglycan (PG) composition. After recombinant production in E. coli, Lys1358 (CHAP) and LysC2 (muramidase) were able to lyse lactococcal cells in turbidity reduction assays, but no activity of LysP2 was detected. The degree of PG acetylation, namely C6-O-acetylation and de-N-acetylation influenced the exolytic activity, being LysC2 more active against cells depleted of the PG deacetylase PgdA and the O-acetyl transferase OatA. On the contrary, both endolysins showed reduced activity on cells with an induced CES response. By measuring several growth parameters of phage c2 on these lactococcal mutants (lytic score, efficiency of plaquing, plaque size and one-step curves), a direct link between the exolytic activity of its endolysin and phage performance could not be stablished

Promoting breastfeeding and interaction of pediatric associations with providers of nutritional products

Pediatric associations have been urged not to interact with and not to accept support from commercial providers of breast milk substitutes (BMSs), based on the assumption that such interaction would lead to diminished promotion and support of breastfeeding. The leadership of seven European pediatric learned societies reviewed the issue and share their position and policy conclusions here. We consider breastfeeding as the best way of infant feeding and strongly encourage its active promotion, protection, and support. We support the World Health Organization (WHO) Code of Marketing of BMSs. Infant formula and follow-on formula for older infants should not be advertised to families or the public, to avoid undermining breastfeeding. With consistently restricted marketing of BMSs, families need counseling on infant feeding choices by well-informed pediatricians. Current and trustworthy information is shared through congresses and other medical education directed and supervised by independent pediatric organizations or public bodies. Financial support from commercial organizations for congresses, educational, and scientific activities of pediatric organizations is an acceptable option if scientific, ethical, societal, and legal standards are followed; any influence of commercial organizations on the program is excluded, and transparency is ensured. Public–private research collaborations for improving and evaluating pharmaceuticals, vaccines, medical devices, dietetic products, and other products and services for children are actively encouraged, provided they are guided by the goal of enhancing child health and are performed following established high standards. We support increasing investment of public funding for research aiming at promoting child health, as well as for medical education.BK is the Else Kröner - Senior Professor of Paediatrics at LMU co-funded by Else Kröner-Fresenius Foundation and LM