GRASP1 ubiquitination regulates AMPA receptor surface expression and synaptic activity in cultured hippocampal neurons.

The synaptic expression of glutamate receptors of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) type is dynamically controlled by interaction with binding partners and auxiliary proteins. These proteins can be regulated by posttranslational modifications, including ubiquitination. In this work, we investigated the regulation of glutamate receptor interacting protein-associated protein 1 (GRASP1) by ubiquitin-dependent mechanisms and its impact on surface expression and activity of synaptic AMPA receptors. Cotransfection of GFP-ubiquitin decreased myc-GRASP1 protein levels in HEK293T cells, and this effect was inhibited upon transfection of an ubiquitin mutant that cannot be ubiquitinated on Lys48. In addition, transfection of cultured hippocampal neurons with GFP-ubiquitin reduced the dendritic levels of endogenous GRASP1 and decreased the surface expression of GluA1 AMPA receptor subunits, an effect that was partly reversed by cotransfection with GRASP1. Similarly, transfection of hippocampal neurons with GFP-ubiquitin decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) mediated by Ca2+ -impermeable AMPA receptors, and this effect was abrogated by cotransfection of GRASP1. Together, the results show a role for ubiquitination in the regulation of the postsynaptic protein GRASP1, which has an impact on the surface distribution of AMPA receptors and on their activity at the synapse.

Microalgae as a Potential Functional Ingredient: Evaluation of the Phytochemical Profile, Antioxidant Activity and In-Vitro Enzymatic Inhibitory Effect of Different Species.

The functional food market has been in a state of constant expansion due to the increasing awareness of the impact of the diet on human health. In the search for new natural resources that could act as a functional ingredient for the food industry, microalgae represent a promising alternative, considering their high nutritional value and biosynthesis of numerous bioactive compounds with reported biological properties. In the present work, the phytochemical profile, antioxidant activity, and enzymatic inhibitory effect aiming at different metabolic disorders (Alzheimer's disease, Type 2 diabetes, and obesity) were evaluated for the species Porphyridium purpureum, Chlorella vulgaris, Arthorspira platensis, and Nannochloropsis oculata. All the species presented bioactive diversity and important antioxidant activity, demonstrating the potential to be used as functional ingredients. Particularly, P. purpureum and N. oculata exhibited higher carotenoid and polyphenol content, which was reflected in their superior biological effects. Moreover, the species P. purpureum exhibited remarkable enzymatic inhibition for all the analyses.

Regulation of NMDA glutamate receptor functions by the GluN2 subunits.

The N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate the flux of calcium (Ca2+ ) into the post-synaptic compartment. Ca2+ influx subsequently triggers the activation of various intracellular signalling cascades that underpin multiple forms of synaptic plasticity. Functional NMDARs are assembled as heterotetramers composed of two obligatory GluN1 subunits and two GluN2 or GluN3 subunits. Four different GluN2 subunits (GluN2A-D) are present throughout the central nervous system; however, they are differentially expressed, both developmentally and spatially, in a cell- and synapse-specific manner. Each GluN2 subunit confers NMDARs with distinct ion channel properties and intracellular trafficking pathways. Regulated membrane trafficking of NMDARs is a dynamic process that ultimately determines the number of NMDARs at synapses, and is controlled by subunit-specific interactions with various intracellular regulatory proteins. Here we review recent progress made towards understanding the molecular mechanisms that regulate the trafficking of GluN2-containing NMDARs, focusing on the roles of several key synaptic proteins that interact with NMDARs via their carboxyl termini.

Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features.

Bromodomain PHD finger transcription factor (BPTF) is the largest subunit of nucleosome remodeling factor (NURF), a member of the ISWI chromatin-remodeling complex. However, the clinical consequences of disruption of this complex remain largely uncharacterized. BPTF is required for anterior-posterior axis formation of the mouse embryo and was shown to promote posterior neuroectodermal fate by enhancing Smad2-activated wnt8 expression in zebrafish. Here, we report eight loss-of-function and two missense variants (eight de novo and two of unknown origin) in BPTF on 17q24.2. The BPTF variants were found in unrelated individuals aged between 2.1 and 13 years, who manifest variable degrees of developmental delay/intellectual disability (10/10), speech delay (10/10), postnatal microcephaly (7/9), and dysmorphic features (9/10). Using CRISPR-Cas9 genome editing of bptf in zebrafish to induce a loss of gene function, we observed a significant reduction in head size of F0 mutants compared to control larvae. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and phospho-histone H3 (PH3) staining to assess apoptosis and cell proliferation, respectively, showed a significant increase in cell death in F0 mutants compared to controls. Additionally, we observed a substantial increase of the ceratohyal angle of the craniofacial skeleton in bptf F0 mutants, indicating abnormal craniofacial patterning. Taken together, our data demonstrate the pathogenic role of BPTF haploinsufficiency in syndromic neurodevelopmental anomalies and extend the clinical spectrum of human disorders caused by ablation of chromatin remodeling complexes.

Microalgae Encapsulation Systems for Food, Pharmaceutical and Cosmetics Applications.

Microalgae are microorganisms with a singular biochemical composition, including several biologically active compounds with proven pharmacological activities, such as anticancer, antioxidant and anti-inflammatory activities, among others. These properties make microalgae an interesting natural resource to be used as a functional ingredient, as well as in the prevention and treatment of diseases, or cosmetic formulations. Nevertheless, natural bioactives often possess inherent chemical instability and/or poor solubility, which are usually associated with low bioavailability. As such, their industrial potential as a health-promoting substance might be severely compromised. In this context, encapsulation systems are considered as a promising and emerging strategy to overcome these shortcomings due to the presence of a surrounding protective layer. Diverse systems have already been reported in the literature for natural bioactives, where some of them have been successfully applied to microalgae compounds. Therefore, this review focuses on exploring encapsulation systems for microalgae biomass, their extracts, or purified bioactives for food, pharmaceutical, and cosmetic purposes. Moreover, this work also covers the most common encapsulation techniques and types of coating materials used, along with the main findings regarding the beneficial effects of these systems.

A Rare Variant Identified Within the GluN2B C-Terminus in a Patient with Autism Affects NMDA Receptor Surface Expression and Spine Density.

NMDA receptors (NMDARs) are ionotropic glutamate receptors that are crucial for neuronal development and higher cognitive processes. NMDAR dysfunction is involved in a variety of neurological and psychiatric diseases; however, the mechanistic link between the human pathology and NMDAR dysfunction is poorly understood. Rare missense variants within NMDAR subunits have been identified in numerous patients with mental or neurological disorders. We specifically focused on the GluN2B NMDAR subunit, which is highly expressed in the hippocampus and cortex throughout development. We analyzed several variants located in the GluN2B C terminus and found that three variants in patients with autism (S1415L) or schizophrenia (L1424F and S1452F) (S1413L, L1422F, and S1450F in rodents, respectively) displayed impaired binding to membrane-associated guanylate kinase (MAGUK) proteins. In addition, we observed a deficit in surface expression for GluN2B S1413L. Furthermore, there were fewer dendritic spines in GluN2B S1413L-expressing neurons. Importantly, synaptic NMDAR currents in neurons transfected with GluN2B S1413L in GluN2A/B-deficient mouse brain slices revealed only partial rescue of synaptic current amplitude. Functional properties of GluN2B S1413L in recombinant systems revealed no change in receptor properties, consistent with synaptic defects being the result of reduced trafficking and targeting of GluN2B S1413L to the synapse. Therefore, we find that GluN2B S1413L displays deficits in NMDAR trafficking, synaptic currents, and spine density, raising the possibility that this mutation may contribute to the phenotype in this autism patient. More broadly, our research demonstrates that the targeted study of certain residues in NMDARs based on rare variants identified in patients is a powerful approach to studying receptor function.SIGNIFICANCE STATEMENT We have used a "bedside-to-bench" approach to investigate the functional regulation of NMDA receptors (NMDARs). Using information from deep sequencing of patients with neurological or psychiatric disorders, we investigated missense variants identified in the intracellular C-terminal domain of the GluN2B NMDAR subunit. We found several variants that displayed altered properties. In particular, one variant identified in a patient with autism, human GluN2B S1415L, displayed reduced surface expression and binding to PSD-95. Furthermore expression of GluN2B S1415L (S1413L in mouse) showed a deficit in rescue of synaptic NMDAR currents and fewer dendritic spines, consistent with other reports of spine abnormalities being associated with autism. More broadly, we demonstrate that using patient data is an effective approach to probing the structure/function relationship of NMDARs.

Electron transfer through arsenite oxidase: Insights into Rieske interaction with cytochrome c.

Arsenic is a widely distributed environmental toxin whose presence in drinking water poses a threat to >140 million people worldwide. The respiratory enzyme arsenite oxidase from various bacteria catalyses the oxidation of arsenite to arsenate and is being developed as a biosensor for arsenite. The arsenite oxidase from Rhizobium sp. str. NT-26 (a member of the Alphaproteobacteria) is a heterotetramer consisting of a large catalytic subunit (AioA), which contains a molybdenum centre and a 3Fe-4S cluster, and a small subunit (AioB) containing a Rieske 2Fe-2S cluster. Stopped-flow spectroscopy and isothermal titration calorimetry (ITC) have been used to better understand electron transfer through the redox-active centres of the enzyme, which is essential for biosensor development. Results show that oxidation of arsenite at the active site is extremely fast with a rate of >4000s-1 and reduction of the electron acceptor is rate-limiting. An AioB-F108A mutation results in increased activity with the artificial electron acceptor DCPIP and decreased activity with cytochrome c, which in the latter as demonstrated by ITC is not due to an effect on the protein-protein interaction but instead to an effect on electron transfer. These results provide further support that the AioB F108 is important in electron transfer between the Rieske subunit and cytochrome c and its absence in the arsenite oxidases from the Betaproteobacteria may explain the inability of these enzymes to use this electron acceptor.

Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor.

Transthyretin (TTR) has a neuroprotective role in the central nervous system (CNS) in Alzheimer's disease (AD) and cerebral ischemia. Increased levels of TTR and activated insulin-like growth factor I receptor (IGF-IR) are associated with reduced neurodegeneration in an AD mouse model. In the present study, we found that TTR and IGF-I have a synergistic effect on activation of one of the IGF-IR signaling pathways. Hippocampus of TTR null mice present decreased levels of phosphorylated IGF-IR and Akt when compared with TTR wild type littermate animals. Cell studies reveal the synergistic effect of TTR and IGF-I in promoting IGF-IR signaling even under glutamate induced toxicity. TTR:IGF-IR complexes are identified and a bio-layer interferometry assay demonstrated an interaction between TTR and IGF-IR with a KD ranging from 99 to 744nM. In summary, our results point to a new TTR role through the IGF-I axis, mediated through TTR-IGF-IR interactions.

Hepatitis C virus NS3-4A inhibits the peroxisomal MAVS-dependent antiviral signalling response.

Hepatitis C virus (HCV) is the cause of one of the most prevalent viral infections worldwide. Upon infection, the HCV genome activates the RIG-I-MAVS signalling pathway leading to the production of direct antiviral effectors which prevent important steps in viral propagation. MAVS localizes at peroxisomes and mitochondria and coordinate the activation of an effective antiviral response: peroxisomal MAVS is responsible for a rapid but short-termed antiviral response, while the mitochondrial MAVS is associated with the activation of a stable response with delayed kinetics. The HCV NS3-4A protease was shown to specifically cleave the mitochondrial MAVS, inhibiting the downstream response. In this study, we have analysed whether HCV NS3-4A is also able to cleave the peroxisomal MAVS and whether this would have any effect on the cellular antiviral response. We show that NS3-4A is indeed able to specifically cleave this protein and release it into the cytosol, a mechanism that seems to occur at a similar kinetic rate as the cleavage of the mitochondrial MAVS. Under these conditions, RIG-I-like receptor (RLR) signalling from peroxisomes is blocked and antiviral gene expression is inhibited. Our results also show that NS3-4A is able to localize at peroxisomes in the absence of MAVS. However, mutation studies have shown that this localization pattern is preferred in the presence of a fully cleavable MAVS. These findings present evidence of a viral evasion strategy that disrupts RLR signalling on peroxisomes and provide an excellent example of how a single viral evasion strategy can block innate immune signalling from different organelles.

Multiple domains in the C-terminus of NMDA receptor GluN2B subunit contribute to neuronal death following in vitro ischemia.

Global cerebral ischemia induces selective degeneration of specific subsets of neurons throughout the brain, particularly in the hippocampus and cortex. One of the major hallmarks of cerebral ischemia is excitotoxicity, characterized by overactivation of glutamate receptors leading to intracellular Ca(2+) overload and ultimately neuronal demise. N-methyl-d-aspartate receptors (NMDARs) are considered to be largely responsible for excitotoxic injury due to their high Ca(2+) permeability. In the hippocampus and cortex, these receptors are most prominently composed of combinations of two GluN1 subunits and two GluN2A and/or GluN2B subunits. Due to the controversy regarding the differential role of GluN2A and GluN2B subunits in excitotoxic cell death, we investigated the role of GluN2B in the activation of pro-death signaling following an in vitro model of global ischemia, oxygen and glucose deprivation (OGD). For this purpose, we used GluN2B(-/-) mouse cortical cultures and observed that OGD-induced damage was reduced in these neurons, and partially prevented in wild-type rat neurons by a selective GluN2B antagonist. Notably, we found a crucial role of the C-terminal domain of the GluN2B subunit in triggering excitotoxic signaling. Indeed, expression of YFP-GluN2B C-terminus mutants for the binding sites to post-synaptic density protein 95 (PSD95), Ca(2+)-calmodulin kinase IIα (CaMKIIα) or clathrin adaptor protein 2 (AP2) failed to mediate neuronal death in OGD conditions. We focused on the GluN2B-CaMKIIα interaction and found a determinant role of this interaction in OGD-induced death. Inhibition or knock-down of CaMKIIα exerted a neuroprotective effect against OGD-induced death, whereas overexpression of this kinase had a detrimental effect. Importantly, in comparison with neurons overexpressing wild-type CaMKIIα, neurons overexpressing a mutant form of the kinase (CaMKII-I205K), unable to interact with GluN2B, were partially protected against OGD-induced damage. Taken together, our results identify crucial determinants in the C-terminal domain of GluN2B subunits in promoting neuronal death in ischemic conditions. These mechanisms underlie the divergent roles of the GluN2A- and GluN2B-NMDARs in determining neuronal fate in cerebral ischemia.

Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study.

BACKGROUND: Neonates admitted to neonatal intensive care units (NICU) are exposed to a wide variety of drugs, most without any data on safety and efficacy. OBJECTIVE: To describe the drugs prescribed to different groups of neonates hospitalized in a NICU, and to analyze off-label use and harmful potential of drugs, in terms of the potential risks. METHODS: This was a six-month retrospective cohort study of drug use in a NICU, with neonates who were inpatients for a period of over 24 hours, and using prescription data from electronic medical records. Drug information found in the package leaflets, in the British National Formulary for Children 2012-2013, and in the Thomson Micromedex database were compared. Drugs and excipients considered potentially harmful were evaluated according to the literature. RESULTS: One hundred ninety-two neonates were included in the study, with a mean gestational age (GA) of 33.3 weeks (SD ± 4.3), 75.0 % were preterm, with an average of 18.8 days of hospitalization (SD ± 18.1), and a total of 3617 neonates-day. 3290 prescriptions were registered, on average 17.1 prescriptions/neonate (SD ± 17.9) and 8.8 drugs/neonate (SD ± 5.9). The number of prescriptions and drugs was higher in neonates with GA <31 weeks (p <0.05). Anti-infectives for systemic use, blood, alimentary tract and metabolism drug groups were more frequent, varying according to the GA. Neonates (99.5 %) were exposed to unlicensed drugs (UL) and off label use (OL), more frequently in GA <28 weeks (p <0.05). Most OL drugs used were indicated for newborns. 15 potentially harmful drugs were used in more than 70 % of the neonates, and most were OL; exposure to harmful excipients occurred in 91.6 % of the neonates, a percentage even higher when considering immature neonates. CONCLUSIONS: Immature neonates in a Brazilian NICU are exposed to a variety of OL, UL and potentially harmful drugs and excipients.

Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome).

Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway.

The pathogen-encoded signalling receptor Tir exploits host-like intrinsic disorder for infection.

The translocated intimin receptor (Tir) is an essential type III secretion system (T3SS) effector of attaching and effacing pathogens contributing to the global foodborne disease burden. Tir acts as a cell-surface receptor in host cells, rewiring intracellular processes by targeting multiple host proteins. We investigated the molecular basis for Tir's binding diversity in signalling, finding that Tir is a disordered protein with host-like binding motifs. Unexpectedly, also are several other T3SS effectors. By an integrative approach, we reveal that Tir dimerises via an antiparallel OB-fold within a highly disordered N-terminal cytosolic domain. Also, it has a long disordered C-terminal cytosolic domain partially structured at host-like motifs that bind lipids. Membrane affinity depends on lipid composition and phosphorylation, highlighting a previously unrecognised host interaction impacting Tir-induced actin polymerisation and cell death. Furthermore, multi-site tyrosine phosphorylation enables Tir to engage host SH2 domains in a multivalent fuzzy complex, consistent with Tir's scaffolding role and binding promiscuity. Our findings provide insights into the intracellular Tir domains, highlighting the ability of T3SS effectors to exploit host-like protein disorder as a strategy for host evasion.

Interrelationships between dissatisfaction with teaching work and depressive symptoms: Structural equation modelling. / Inter-relações entre insatisfação com o trabalho docente e sintomas depressivos: modelagem com equações estruturais.

The objective of this article is to evaluate the interrelationships of factors associated with depressive symptoms (DS) in teachers, considering dissatisfaction with the teaching job as a possible mediator. This was a cross-sectional study using data from 700 teachers from the public school system of a Brazilian municipality. The outcome of interest was DS, as assessed using the Beck Depression Inventory (BDI). Direct and indirect interrelationships between the outcome and dissatisfaction with work, age, income, lifestyle and adiposity were tested. These variables composed the operational model tested by structural equation modelling. Older age (ß=0.12) and greater dissatisfaction with work (ß=0.12) were directly associated with DS. A more favourable lifestyle (ß=-0.60) and adiposity (ß=-0.10) were associated with a lower occurrence of DS. The variables lifestyle (ß=-0.06) and adiposity (ß=-0.02) also had negative indirect effects on DS, mediated by job dissatisfaction. The structural equation model tested identified interrelationships that influenced DS. Dissatisfaction with teaching work was associated with DS and mediated the relationship of other factors with such symptoms.

O objetivo deste artigo é avaliar inter-relações de fatores associados a sintomas depressivos (SD) em professores, considerando a insatisfação com o trabalho docente como possível mediador. Estudo transversal utilizando dados de 700 professores da rede pública de ensino de um município brasileiro. O desfecho de interesse foi SD aferido pelo Inventário de Depressão de Beck (BDI). Foram testadas inter-relações diretas e indiretas entre o desfecho e insatisfação com o trabalho, idade, renda, estilo de vida e adiposidade. Essas variáveis compuseram modelo operacional testado por meio de modelagem de equações estruturais. A maior idade (ß=0,12) e a maior insatisfação com o trabalho (ß=0,12) associaram-se diretamente aos SD. Já o estilo de vida mais favorável (ß=-0,60) e a adiposidade (ß=-0,10), associaram-se a menor ocorrência de SD. As variáveis estilo de vida (ß=-0,06) e adiposidade (ß=-0,02) também apresentaram efeitos indiretos negativos nos SD, mediados pela insatisfação com o trabalho. O modelo de equação estrutural testado identificou inter-relações que influenciaram os SD. A insatisfação com o trabalho docente associou-se aos SD e mediou a relação de outros fatores sobre tais sintomas.

Generalized Lymphadenopathy as the First Manifestation of Systemic Lupus Erythematosus.

Lymphadenopathy (LAP) is a common but nonspecific feature of many diseases, representing a vast spectrum of etiologies such as infectious or inflammatory diseases, malignancies, and drugs. In systemic lupus erythematosus (SLE), it can be the first manifestation. We present the case of a 20-year-old female with a history of fever, night sweats, anorexia, and asthenia for five months. She also had diffuse generalized LAP. Although malignant etiologies were our major concern, an extensive workup for malignancy and infections was unrevealing. However, an autoimmune workup led to the diagnosis of SLE. This case shows that SLE can present as generalized LAP with constitutional symptoms, and hence it should be considered in the differential diagnosis.

The role of NMDA receptor and neuroligin rare variants in synaptic dysfunction underlying neurodevelopmental disorders.

Many genes encoding synaptic proteins are associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorders (ASDs), intellectual disability (ID), and epilepsy. Here we review recent studies on the synaptic effects of disease-associated rare variants identified in two families of synaptic proteins: NMDA receptors (NMDARs) and the postsynaptic adhesion molecules neuroligins (NLGNs). Many NMDAR subunit genes (GRINs) are highly intolerant to variation, and both gain-of-function (GOF) and loss-of-function (LOF) variants are implicated in disease. NLGN genes are also associated with ASDs, and in some cases, contribute to the male bias identified in these patients. Understanding the molecular basis of synaptic dysfunction of rare variants in these genes will help the design of new therapeutic approaches.

Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit.

NMDA receptor (NMDAR)-dependent Ca2+ influx underpins multiple forms of synaptic plasticity. Most synaptic NMDAR currents in the adult forebrain are mediated by GluN2A-containing receptors, which are rapidly inserted into synapses during long-term potentiation (LTP); however, the underlying molecular mechanisms remain poorly understood. In this study, we show that GluN2A is phosphorylated at Ser-1459 by Ca2+/calmodulin-dependent kinase IIα (CaMKIIα) in response to glycine stimulation that mimics LTP in primary neurons. Phosphorylation of Ser-1459 promotes GluN2A interaction with the sorting nexin 27 (SNX27)-retromer complex, thereby enhancing the endosomal recycling of NMDARs. Loss of SNX27 or CaMKIIα function blocks the glycine-induced increase in GluN2A-NMDARs on the neuronal membrane. Interestingly, mutations of Ser-1459, including the rare S1459G human epilepsy variant, prolong the decay times of NMDAR-mediated synaptic currents in heterosynapses by increasing the duration of channel opening. These findings not only identify a critical role of Ser-1459 phosphorylation in regulating the function of NMDARs, but they also explain how the S1459G variant dysregulates NMDAR function.

An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIα Phosphorylation of GluN2A and NMDA Receptor Trafficking.

Rare variants in GRIN genes, which encode NMDAR subunits, are strongly associated with neurodevelopmental disorders. Among these, GRIN2A, which encodes the GluN2A subunit of NMDARs, is widely accepted as an epilepsy-causative gene. Here, we functionally characterize the de novo GluN2A-S1459G mutation identified in an epilepsy patient. We show that S1459 is a CaMKIIα phosphorylation site, and that endogenous phosphorylation is regulated during development and in response to synaptic activity in a dark rearing model. GluN2A-S1459 phosphorylation results in preferential binding of NMDARs to SNX27 and a corresponding decrease in PSD-95 binding, which consequently regulates NMDAR trafficking. Furthermore, the epilepsy-associated GluN2A-S1459G variant displays defects in interactions with both SNX27 and PSD-95, resulting in trafficking deficits, reduced spine density, and decreased excitatory synaptic transmission. These data demonstrate a role for CaMKIIα phosphorylation of GluN2A in receptor targeting and implicate NMDAR trafficking defects as a link to epilepsy.

[Arterial Hypertension and work among teachers of basic education in the public-school system]. / Hipertensão Arterial e trabalho entre docentes da educação básica da rede pública de ensino.

The scope of this paper was to investigate the relationship between Arterial Hypertension (AH) and the occupational profile of teachers of basic public education and present a theoretical model. A probabilistic sample was adopted by clusters, with AH as the dependent variable. The independent variables were grouped in thematic blocks (Sociodemographic Characteristics, Occupational Profile, Behaviors and Health Outcomes) that composed the theoretical model. The analyses were corrected by the sample design. Hierarchical logistic regression was conducted. The prevalence of AH was 25%, and 58% reported dissatisfaction with the work. There was a higher probability of AH among older teachers (OR = 3.7), without postgraduate qualification (OR = 1.4), who also worked in the private network (OR = 2.6), who had a higher salt intake (OR = 1.7), with a high waist-hip ratio (OR = 1.9) and hypercholesterolemia / hypertriglyceridemia (OR = 1, 5) and a lower chance among females (OR = 0.5), who had other work activity (OR = 0.6) and were dissatisfied with the work (OR = 0.6). Thus, the occupational profile of teachers had an influence on AH. The relationship between work and teacher health demands attention and care, with measures that preserve and promote the health and well-being of teachers.

Objetivou-se investigar a relação entre Hipertensão Arterial (HA) e perfil ocupacional de docentes da educação básica pública e apresentar modelo teórico. Adotou-se amostra probabilística por conglomerados. A HA foi a variável dependente. As variáveis independentes foram agrupadas em blocos temáticos (Características Sociodemográficas, Perfil Ocupacional, Comportamentos e Desfechos em Saúde), que compuseram o modelo teórico. As análises foram corrigidas pelo desenho amostral. Foi conduzida regressão logística hierarquizada. A prevalência de HA foi de 25%, enquanto que 58% apresentaram insatisfação com o trabalho. Houve maior chance de HA entre os docentes mais velhos (OR = 3,7), sem pós-graduação (OR = 1,4), que atuavam também na rede privada (OR = 2,6), que apresentavam maior consumo de sal (OR = 1,7), com sobrepeso (OR = 2,1) / obesidade (OR = 7,2), com relação cintura-quadril elevada (OR = 1,9) e com hipercolesterolemia/hipertrigliceridemia (OR = 1,5) e menor chance entre os do sexo feminino (OR = 0,5), que exerciam outra atividade de trabalho (OR = 0,6) e insatisfeitos com o trabalho (OR = 0,6). Assim, o perfil ocupacional docente apresentou influência sobre a HA. A relação trabalho e saúde docente carece de atenção e cuidado, com adoção de medidas que preservem e promovam sua saúde e seu bem-estar.

Avaliação de indicadores sociais e de saúde em municípios de Minas Gerais conforme tipologia rural-urbano / Assessment of social and health indicators in municipalities of Minas Gerais according to the rural-urban typology

RESUMO O presente artigo tem o objetivo de avaliar indicadores sociais e de saúde de municípios conforme a tipologia rural-urbano. Trata-se de estudo ecológico que utilizou dados oficiais de acesso público dos 853 municípios do estado de Minas Gerais, Brasil. Foram conduzidas análises descritivas e bivariadas através da Regressão de Poisson e Teste de Kruskal-Wallis. Do total de municípios, 547 (64,12%) são rurais. A maior média do Índice de Desenvolvimento Humano Municipal (IDH-M) foi observada entre os municípios urbanos. A maior média de cobertura da Estratégia Saúde da Família (ESF) foi verificada entre os municípios rurais, nos quais também foram demonstrados os melhores resultados para os indicadores de mortalidades infantil, prematura e por causas evitáveis, homogeneidade vacinal e prevalência de desnutrição. Os achados deste estudo evidenciam que uma maior cobertura da ESF está associada à ocorrência de melhores condições gerais de vida e de saúde das populações atendidas em municípios de tipologia rural. Recomenda-se aos gestores de saúde o fomento à consolidação da ESF em comunidades com contextos socioeconômicos e culturais desfavoráveis, como localidades rurais remotas e aglomerados urbanos, e o estabelecimento de ações intersetoriais com impacto positivo na saúde.

ABSTRACT This article aims to evaluate social and health indicators of municipalities according to the rural-urban typology. This is an ecological study that used official publicly accessible data from the 853 municipalities in the state of Minas Gerais, Brazil. Descriptive and bivariate analysis were carried out using Poisson Regression and Kruskal-Wallis Test. 547 (64.12%) are rural municipalities. The highest average of the Municipal Human Development Index (MHDI) was observed among urban municipalities. The highest average coverage of the Family Health Strategy (FHS) was found among rural municipalities. In these municipalities, the best results were shown for the indicators of infant mortality, premature mortality and mortality from preventable causes, vaccine homogeneity and prevalence of malnutrition. The findings of this study show that greater FHS coverage is associated with the occurrence of better general living and health conditions in the populations served in rural municipalities. It is recommended that health managers encourage the consolidation of the FHS in communities with unfavorable socioeconomic and cultural contexts, such as remote rural locations and urban agglomerations, and the establishment of intersectoral actions with a positive impact on health.