SPARC triggers a cell-autonomous program of synapse elimination

Elimination of the excess synaptic contacts established in the early stages of neuronal development is required to refine the function of neuronal circuits. Here we investigate whether secreted protein acidic and rich in cysteine (SPARC), a molecule produced by glial cells, is involved in synapse removal. SPARC production peaks when innervation of the rat superior cervical ganglion and the tail of Xenopus tropicalis tadpoles are remodeled. The formation of new cholinergic synapses in autaptic single-cell microcultures is inhibited by SPARC. The effect resides in the C-terminal domain, which is also responsible for triggering a concentration- and time-dependent disassembly of stable cholinergic synapses. The loss of synaptic contacts is associated with the formation of retracted axon terminals containing multivesicular bodies and secondary lysosomes. The biological relevance of in vitro results was supported by injecting the tail of Xenopus tropicalis tadpoles with peptide 4.2, a 20-aa sequence derived from SPARC that mimics full-length protein effects. Swimming was severely impaired at ∼5 h after peptide application, caused by the massive elimination of neuromuscular junctions and pruning of axonal branches. Effects revert by 6 d after injection, as motor innervation reforms. In conclusion, SPARC triggers a cell-autonomous program of synapse elimination in cholinergic neurons that likely occurs when protein production peaks during normal development

Presynaptic clathrin levels are a limiting factor for synaptic transmission

To maintain communication, neurons must recycle their synaptic vesicles with high efficiency. This process places a huge burden on the clathrin-mediated endocytic machinery, but the consequences of this are poorly understood. We found that the amount of clathrin in a presynaptic terminal is not fixed. During stimulation, clathrin moves out of synapses as a function of stimulus strength and neurotransmitter release probability, which, together with membrane coat formation, transiently reduces the available pool of free clathrin triskelia. Correlative functional and morphological experiments in cholinergic autapses established by superior cervical ganglion neurons in culture show that presynaptic terminal function is compromised if clathrin levels fall by 20% after clathrin heavy chain knock down using RNAi. Synaptic transmission is depressed due to a reduction of cytoplasmic and readily releasable pools of vesicles. However, synaptic depression reverts after dialysis of exogenous clathrin, thus compensating RNAi-induced depletion. Lowering clathrin levels also reduces quantal size, which occurs concomitantly with a decrease in the size of synaptic vesicles. Large dense-core vesicles are unaffected by clathrin knock down. Together, our results show that clathrin levels are a dynamic property of presynaptic terminals that can influence short-term plasticity in a stimulus-dependent manner

Acute complexin knockout abates spontaneous and evoked transmitter release

SNARE-mediated synaptic vesicle (SV) fusion is controlled by multiple regulatory proteins that determine neurotransmitter release efficiency. Complexins are essential SNARE regulators whose mode of action is unclear, as available evidence indicates positive SV fusion facilitation and negative 'fusion clamp'-like activities, with the latter occurring only in certain contexts. Because these contradictory findings likely originate in part from different experimental perturbation strategies, we attempted to resolve them by examining a conditional complexin-knockout mouse line as the most stringent genetic perturbation model available. We found that acute complexin loss after synaptogenesis in autaptic and mass-cultured hippocampal neurons reduces SV fusion probability and thus abates the rates of spontaneous, synchronous, asynchronous, and delayed transmitter release but does not affect SV priming or cause 'unclamping' of spontaneous SV fusion. Thus, complexins act as facilitators of SV fusion but are dispensable for 'fusion clamping' in mammalian forebrain neurons

Medios audiovisuales de servicio público y desinformación. Principales políticas y estrategias contra las noticias falsas

The increase in false news, which aims to distort reality and create confusion between truth and lies, has become a global social problem. The verification of information has emerged as a fundamental element for the journalistic profession and some experiences have already been launched from various media, platforms and organizations. The European Union has presented an Action Plan - in force since 2019 - to counter any post-truth campaign, based on an increase in resources, coordination, the elaboration of a code of good practice and the creation of verification and contrast groups. of data. In this context, the role of publicly owned audiovisual media does not have to be secondary and must lead a coordinated media literacy process in each Member State to cut the increase in disinformation. The objective of this research is to analyze the policies and strategies that the main European public radio televisions are applying to strengthen the fight against false news. The methodological design to achieve this purpose starts from the systematic review of the scientific literature, which has made it possible to know the main contributions to the state of the question and to generate a story on this topic, which is of growing interest in the area of ​​Communication but not yet comprehensively addressed. In addition, gray literature (memoirs, reports and other documents) and actions carried out by the public televisions under study are analyzed. The results reveal that new policies and strategies are emerging in the public service audiovisual media associated with the fight against disinformation and fake news

Orienteering race with QR codes in Physical Education

Monográfico con el título: "Actividades Físicas en el Medio Natural (1ª parte)"Resumen basado en el de la publicaciónTítulo, resumen y palabras clave también en inglésEl deporte de orientación es muy practicado en la actualidad, incluido en el ámbito educativo. Los actuales avances tecnológicos permiten integrar la tecnología en la práctica de la orientación, creando así interesantes e innovadoras actividades. En este sentido, se pretende mostrar una experiencia didáctica de una carrera de orientación con la integración de los códigos QR (Quick Response). Se trata de una práctica en el medio natural, en la cual se integran los códigos QR como medio de evaluación de conocimientos teóricos. La carrera está compuesta de 13 controles y en cada uno de ellos hay un código QR que al leerlo muestra una pregunta tipo test. También se muestran y detallan los pasos a seguir para organizar este tipo de actividades, siendo de gran utilidad para docentes que deseen ponerla en práctica. Estas innovaciones suponen para el alumnado un extra de motivación y hacen la actividad más atractiva, consiguiendo una mayor implicación. Asimismo, se consigue que los alumnos conozcan otras posibilidades de utilización de los dispositivos móviles y su uso adecuado.ES

Medios audiovisuales de servicio público y desinformación. Principales políticas y estrategias contra las noticias falsas

The increase in false news, which aims to distort reality and create confusion between truth and lies, has become a global social problem. The verification of information has emerged as a fundamental element for the journalistic profession and some experiences have already been launched from various media, platforms and organizations. The European Union has presented an Action Plan - in force since 2019 - to counter any post-truth campaign, based on an increase in resources, coordination, the elaboration of a code of good practice and the creation of verification and contrast groups. of data. In this context, the role of publicly owned audiovisual media does not have to be secondary and must lead a coordinated media literacy process in each Member State to cut the increase in disinformation. The objective of this research is to analyze the policies and strategies that the main European public radio televisions are applying to strengthen the fight against false news. The methodological design to achieve this purpose starts from the systematic review of the scientific literature, which has made it possible to know the main contributions to the state of the question and to generate a story on this topic, which is of growing interest in the area of ​​Communication but not yet comprehensively addressed. In addition, gray literature (memoirs, reports and other documents) and actions carried out by the public televisions under study are analyzed. The results reveal that new policies and strategies are emerging in the public service audiovisual media associated with the fight against disinformation and fake news

Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregulated at high AP frequencies to balance SV consumption. We show that Munc13-1-an essential SV priming protein-regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotransmission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

Adipokines, Biomarkers of Endothelial Activation, and Metabolic Syndrome in Patients with Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS

Brain Functional Connectivity Is Modified By A Hypocaloric Mediterranean Diet And Physical Activity In Obese Women

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 +/- 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m(2)) was 38.15 +/- 4.7 vs. 34.18 +/- 4.5 (p < 0.02), and body weight (kg) was 98.5 +/- 13.1 vs. 88.28 +/- 12.2 (p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001), left posterior cingulate (p < 0.001), and right posterior cingulate (p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025); and decreased connectivity between the left and right posterior cingulate (p < 0.04). Results were considered significant at a voxel-wise threshold of p <= 0.05, and a cluster-level family-wise error correction for multiple comparisons of p <= 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity ( the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients