The RabGAP TBC1D14 regulates autophagosome formation via recycling endosomes and Rab11

Autophagy is a bulk degradation process characterised by the formation of double membrane vesicles called autophagosomes. Autophagosomes derive from a small precursor structure called phagophore, which is expanded to enclose a portion of cytoplasm or organelle, and finally fuses with the endo-lysosomal system to acquire degradative capacity. Autophagy is often studied as a response to starvation, since the degraded components can be re-used for biosynthetic pathways. However, in multicellular organisms, it has many additional functions in tissue homeostasis, during development, in infection and immunity, and in programmed cell death. Regarding autophagy many questions remain such as the origin of the autophagosomal membrane, the mechanism of phagophore extension and many of the signalling pathways that lead to autophagosome assembly. To better understand the membrane trafficking events involved in autophagosome formation I did an over-expression screen for Rab GTPase activating proteins (RabGAPs) inhibiting this process. RabGAPs act inhibitory on Rab GTPases, which are major regulators of intracellular membrane traffic. I have identified 11 RabGAPs that inhibit autophagosome formation, one of which is TBC1D14, which binds to ULK1, an important kinase for initiation of autophagy. TBC1D14 also binds to Rab11 and tubulates recycling endosomes when over-expressed. I found that both ULK1 and another essential autophagy protein mAtg9 localise to recycling endosomes under normal conditions. I propose that recycling endosomes can signal through both ULK1 and mAtg9 to initiate autophagosome formation upon starvation and may be important in monitory cellular nutrient status, and/or provide membrane to autophagosomes. Investigating the role of ULK1 in vivo, I found that ULK1 knock-out mice are able to undergo basal autophagy as assessed by LC3 lipidation in various tissues. However, ULK1 knock-out mice have less CD4 and CD8-positive mature T cells and their response to TCR stimulation is impaired compared to T cells from wild type animals

ARHGAP22 DISRUPTION AFFECTS RAC1 SIGNALING PATHWAY AND RESULTS IN ALTERED FORMATION AND FUNCTION OF GLUTAMATERGIC SYNAPSES IN MOUSE HIPPOCAMPUS

The regulation of actin cytoskeleton operated by RhoGTPases is crucial for neuronal morphogenesis, especially for neurite elongation and branching, synaptogenesis and synaptic plasticity. Dysregulation of RhoGTPases leads to neuronal dysfunctions including intellectual disability, schizofrenia and Alzheimer disease. Rac1 is a member of the RhoGTPase family and it has been demonstrated to positively regulate dendritogenesis and dendritic spines formation and maturation. As well as other RhoGTPases, Rac1 activity is regulated principally by two kinds of molecules: GEFs (guanine nucleotide exchange factors) and GAPs (GTPase activating proteins). Arhgap22 protein is a specific Rac1-Gap that promotes the inactivation of Rac1. Although it was previously reported that Arhgap22 transcripts is present in murine brain, its functions in neurons have not been studied yet. Here, we reported that Arhgap22 is expressed in mouse brain in a precise spatio-temporal window. Moreover, taking advantage of an animal mouse model knock out (KO) for Arhgap22, we described the effects of its silencing in hippocampal neurons. In vivo, Arhgap22 disruption led to an increase level of activated Rac1 and its downstream pathways, with a subsequent increase in dendritic spine density in CA1 region of hippocampus. Additionally, Arhgap22 lacking mice presented reduced AMPA receptors in the post-synaptic density of excitatory synapses and this alteration was reflected by the impairment in the induction and mainteinance of long-term potentiation (LTP). Arhgap22 KO mice presented also defects in cognitive tasks and decreased anxiety-like behaviours. In a nutshell, the results of this work suggested that Arhgap22 is a key regulator of Rac1 signaling and that affects the maturation of excitatory synapses, synaptic plasticity and cognitive functions

Oswald de Andrade and Oficina Theatre: The Candle king on stage

This article aims to understand the form and content of the play “O Rei da Vela'' written by Oswald de Andrade, a pioneering author of Modernism,  and played by Teatro Oficina, idealized by José Celso Martinez. In different historical contexts, Zé Celso and Oswald de Andrade innovated the theater: Oswald through the critical content in his theatrical text and Zé Celso through the creative form used to stage this text. We seek to comprehend how the Teatro Oficina used the Oswaldian text to broaden its critical spirit, by means of language and theatrical tools.Esse artigo busca refletir sobre a montagem da peça teatral “O Rei da Vela”, escrita por Oswald de Andrade, um dos precursores do modernismo, pelo Teatro Oficina, idealizado por José Celso Martinez. Em períodos históricos diferentes, Zé Celso e Oswald de Andrade inovaram o teatro: Oswald por intermédio do conteúdo crítico de seu texto dramatúrgico, e Zé Celso por via da forma utilizada para a montagem criativa do texto. Buscaremos compreender como o Teatro Oficina utilizou o texto oswaldiano para ampliar seu substrato crítico, por meio da linguagem e recursos teatrais

Ecological aspects of the dispersal of a melastomataceae by marmosets and howler monkeys (Primates : Platyrrhini) in a semideciduous forest of southeastern Brazil

Nous avons étudié le comportement alimentaire et l'effet de la digestion sur les graines d'un arbre néotropical (Miconia cinnamomifolia) par les primates (Alouatta fusca fusca et Callithrix penicillata) dans une forêt du sud-est du Brésil. Alouatta fusca consomme en partie des fruits immatures et les taux de germination des graines ingérées sont réduits. Callithrix penicillata est un meilleur disperseur des graines de M. cinnamomifolia. Ces résultats confortent l'hypothèse selon laquelle les petites graines sont disséminées par des petits animaux

Endoscopic anatomy of the fourth ventricle

Object Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the "inside" view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery. Methods The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation. Results The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen. Conclusions On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle

A Case of Disseminated Polycystic Dilated Perivascular Spaces Presenting with Dementia and Parkinsonism

The perivascular spaces (PVSs) of the brain are lined with pia and contain interstitial fluid. In general, PVSs are small, asymptomatic, and identifiable at all ages. When PVSs are significantly enlarged, they can produce various clinical manifestations such as headache and dizziness. A 67-year-old man was admitted with cognitive impairment and gait disturbance with a 5-month history. Brain MRI showed multiple cystic PVSs in periventricular and subcortical white matter of both hemispheres. Medication with dopaminergic agents produced a moderate clinical improvement, while anticholinesterase was not effective. This case suggests that disseminated polycystic dilated PVSs may present with dementia and Parkinsonism

A light on the dark side: In vivo endoscopic anatomy of the posterior third ventricle and its variations in hydrocephalus

Objective: Despite the technological advancements of neurosurgery, the posterior part of the third ventricle has always been the "dark side"of the ventricle. However, flexible endoscopy offers the opportunity for a direct, in vivo inspection and detailed description of the posterior third ventricle in physiological and pathological conditions. The purposes of this study were to describe the posterior wall of the third ventricle, detailing its normal anatomy and surgical landmarks, and to assess the effect of chronic hydrocephalus on the anatomy of this hidden region. Methods: The authors reviewed the video recordings of 59 in vivo endoscopic explorations of the posterior third ventricle to describe every identifiable anatomical landmark. Patients were divided into 2 groups based on the absence or presence of a chronic dilation of the third ventricle. The first group provided the basis for the description of normal anatomy. Results: The following anatomical structures were identified in all cases: adytum of the cerebral aqueduct, posterior commissure, pineal recess, habenular commissure, and suprapineal recess. Comparing the 2 groups of patients, the authors were able to detect significant variations in the shape of the adytum of the cerebral aqueduct and in the thickness of the habenular and posterior commissures. Exploration with sodium fluorescein excluded the presence of any fluorescent area in the posterior third ventricle, other than the subependymal vascular network. Conclusions: The use of a flexible scope allows the complete inspection of the posterior third ventricle. The anatomical variations caused by chronic hydrocephalus might be clinically relevant, in light of the commissure functions

Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and adult populations: a systematic review and meta-analysis

Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days-87 years]. Although flexible ETV had a higher incidence of failure in adults (flexible: 54%, 95%CI: 22-82% vs rigid: 20%, 95%CI: 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus