Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy

AMNÉSIA GLOBAL TRANSITÓRIA: EPIDEMIOLOGIA, FISIOPATOLOGIA, CLÍNICA E TERAPÊUTICA

A amnésia global transitória (AGT) é um quadro súbito de amnésia glo- bal, não acompanhada de outros déficits neurológicos, com duração de duas a 24 horas e cuja recuperação se dá espontaneamente. A incidência na população geral está estimada em 5-10 casos/100.000 pessoas/ano. Diferentes mecanismos fisiopatológicos, como fatores vasculares ou epiléticos, têm sido propostos para explicar a AGT, sendo consensual que haja acometimento transitório de regiões do hipocampo e do giro para-hipocampal. Além da amnésia anterógrada acompanhada por amnésia retrógra- da, o paciente apresenta desorientação (tempo/espaço), estando pre- servadas outras habilidades cognitivas, como memória semântica e capacidades visuo-construtivas. Esses déficits tendem a remitir após 24h, sendo o prognóstico favorável na maioria dos casos. O diagnós- tico diferencial de AGT é amplo e diversas condições clínicas, como eventos cérebro-vasculares, epilepsias, infecções e intoxicações po- dem mimetizá-lo, de modo que uma investigação clínica cuidadosa é imperativa. As recorrências não são frequentes nos quadros típicos. A AGT não requer tratamento específico, mas devem ser tratados fa- tores de risco cardiovascular eventualmente identificados durante a propedêutica de AGT. O clínico deve esclarecer o paciente a respeito do caráter benigno da AGT. Estudos com seguimento longitudinal dos pacientes são necessários para maior compreensão dos mecanismos fisiopatológicos da AGT e para melhor compreensão clínica e neuro- biológica dos déficits cognitivos apresentados por esses pacientes.

Focal persistence of soil-transmitted helminthiases in impoverished areas in the State of Piaui, Northeastern Brazil

This study aims to describe the prevalence, distribution, and factors associated with soil-transmitted helminthiases (STHs) in rural localities in Piaui, Brazil. Two cross-sectional surveys (n=605 subjects; 172 families) were carried out in order to obtain socio-demographic, anthropometric, spatial and parasitological data. Parasites were evaluated using Kato-Katz and centrifugal sedimentation techniques. Eggs were measured to assess infection with zoonotic Strongylida parasites. Kernel maps were constructed with Q-GIS. The prevalence of hookworm infection was 12.4% (75/605). Other helminthes found were Trichuris trichiura (n=1; 0.2%) and Hymenolepis nana (n=1; 0.2%). The hookworm positivity rate was significantly lower among subjects who had used albendazole when compared with individuals who had not used anthelmintics or had used antiprotozoal drugs in the last 6 months (8/134 [6.0%] vs. 59/415 [14.2%]; p=0.009). A total of 39/172 (22.7%) families had at least one infected member. The association between the number of dwellers and hookworm positivity in the family was present in a logistic regression multivariate model. Assessment of worm burdens showed 92.2% light, 6.2% moderate, and 1.6% heavy infections. Hookworm eggs (n=34) measured 57.2 - 75.4 µm in length and 36.4 - 44.2 µm in width (mean ± SD = 65.86 ± 4.66 µm L and 40.05 ± 1.99 µm W), commensurate with human hookworms. Hotspots suggest that transmission has a focal pattern. STHs persist in impoverished rural areas in Northeastern Brazil where currently available control strategies (mass drug administration) apparently do not allow the elimination of the infection

Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a cochaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes

Cephalopod fauna of the Pacific Southern Ocean using Antarctic toothfish (Dissostichus mawsoni) as biological samplers and fisheries bycatch specimens

Cephalopods are an important component of Southern Ocean food webs but studies analysing their habitat and trophic ecology are scarce. Here, we use the Antarctic toothfish Dissostichus mawsoni as a biological sampler of Southern Ocean’s cephalopods in the Ross, Amundsen, and D’Urville Seas. Ten cephalopod taxa were identified in the diet of the Antarctic toothfish, with Pareledone turqueti and Moroteuthopsis longimana being the only species present in all the three studied areas. DNA analysis conducted on squid flesh samples allowed identification of eight and two specimens of Mesonychoteuthis hamiltoni and M. longimana, respectively, proving this technique as a potential tool to improve the knowledge of cephalopods biodiversity and biogeography in the Southern Ocean. Stable isotopes were used to compare the habitat (δ13C) and trophic ecology (δ15N) between two life-stages of the two most abundant squid species (M. longimana and Psychroteuthis glacialis) from the D’Urville Sea (both squid species) and Amundsen Sea (only P. glacialis). Higher δ13C values in M. longimana suggest that this species inhabits waters near the Antarctic Polar Front, with incursions into sub-Antarctic waters, whilst P. glacialis spends its entire life in Antarctic waters. The most recently deposited part of the beak is enriched in 15N suggesting an increase in trophic level during squid growth. These results give us the first insights into the bathyal distribution of cephalopods in the Amundsen and D’Urville Seas, as well as into the ontogenetic changes of two of the most consumed squid species by top predators in this region. Such results are an important step towards improving the biogeography of Antarctic cephalopods, being of utmost importance to understand the biodiversity, food web structure, and functioning of this regioninfo:eu-repo/semantics/publishedVersio

Single Nucleotide Polymorphisms in the Wnt and BMP Pathways and Colorectal Cancer Risk in a Spanish Cohort

BACKGROUND: Colorectal cancer (CRC) is considered a complex disease, and thus the majority of the genetic susceptibility is thought to lie in the form of low-penetrance variants following a polygenic model of inheritance. Candidate-gene studies have so far been one of the basic approaches taken to identify these susceptibility variants. The consistent involvement of some signaling routes in carcinogenesis provided support for pathway-based studies as a natural strategy to select genes that could potentially harbour new susceptibility loci. METHODOLOGY/PRINCIPAL FINDINGS: We selected two main carcinogenesis-related pathways: Wnt and BMP, in order to screen the implicated genes for new risk variants. We then conducted a case-control association study in 933 CRC cases and 969 controls based on coding and regulatory SNPs. We also included rs4444235 and rs9929218, which did not fulfill our selection criteria but belonged to two genes in the BMP pathway and had consistently been linked to CRC in previous studies. Neither allelic, nor genotypic or haplotypic analyses showed any signs of association between the 37 screened variants and CRC risk. Adjustments for sex and age, and stratified analysis between sporadic and control groups did not yield any positive results either. CONCLUSIONS/SIGNIFICANCE: Despite the relevance of both pathways in the pathogenesis of the disease, and the fact that this is indeed the first study that considers these pathways as a candidate-gene selection approach, our study does not present any evidence of the presence of low-penetrance variants for the selected markers in any of the considered genes in our cohort

Anestesia Regional vs. Anestesia Geral em Procedimentos Ginecológicos: Análise Comparativa

Objective: The aim of the article is to conduct a comparative review between regional and general anesthesia in gynecological procedures, exploring intraoperative risks, complications, patient satisfaction, and economic impacts. The goal is to provide a comprehensive analysis to guide clinical decision-making, considering both clinical and economic aspects in the choice of the most appropriate anesthetic modality. Introduction: The importance of choosing between regional and general anesthesia in gynecological procedures is emphasized. It underscores the complexity of the decision, considering risks, complications, and the need for a personalized approach. The significance of a comprehensive analysis is highlighted to guide clinical practices and promote informed decisions in the pursuit of safe and effective anesthesia. Methodology: An integrative review was conducted on the PubMed, Scielo, and BVS databases, using specific terms such as "Regional Anesthesia," "General Anesthesia," and "Gynecological Surgical Procedures." The use of boolean operators AND and OR was adopted to refine the search, aiming to identify relevant clinical studies, systematic reviews, integrative reviews, and meta-analyses, with priority given to original articles. Conclusion: The review highlights the complexity in choosing between regional and general anesthesia in gynecological procedures, emphasizing risks, patient satisfaction, and economic impacts. Flexibility in approach, effective communication, and strategies for financial optimization are crucial for patient-centered anesthesia practice. The ongoing pursuit of a balance between clinical efficacy and economic efficiency is fundamental to enhance the quality of anesthesia care.Objetivo: O objetivo do artigo é realizar uma revisão comparativa entre anestesia regional e geral em procedimentos ginecológicos, explorando riscos intraoperatórios, complicações, satisfação da paciente e impactos econômicos. O intuito é fornecer uma análise abrangente para orientar a tomada de decisão clínica, considerando aspectos clínicos e econômicos na escolha da modalidade anestésica mais apropriada. Introdução: Destaca-se a importância da escolha entre anestesia regional e geral em procedimentos ginecológicos. Enfatiza a complexidade da decisão, considerando riscos, complicações e a necessidade de uma abordagem personalizada. Importância da análise abrangente para orientar práticas clínicas e promover decisões informadas na busca por uma anestesia segura e eficaz. Metodologia: Conduziu-se uma revisão integrativa nas bases de dados PubMed, Scielo e BVS, empregando termos específicos como "Anestesia Regional," "Anestesia Geral," e "Procedimentos Cirúrgicos em Ginecologia." A utilização de operadores booleanos AND e OR foi adotada para aperfeiçoar a busca, visando identificar estudos clínicos, revisões sistemáticas, revisões integrativas e meta-análises pertinentes, com prioridade para artigos originais. Conclusão: A revisão evidencia a complexidade na escolha entre anestesia regional e geral em procedimentos ginecológicos, ressaltando riscos, satisfação da paciente e impactos econômicos. A flexibilidade na abordagem, comunicação eficaz e estratégias para otimização financeira são cruciais para uma prática anestésica centrada no paciente. A constante busca por equilíbrio entre eficácia clínica e eficiência econômica é fundamental para aprimorar a qualidade dos cuidados anestésicos

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to “turn down” neuronal circuits controlling locomotion

Strong Carbon Features and a Red Early Color in the Underluminous Type Ia SN 2022xkq

We present optical, infrared, ultraviolet, and radio observations of SN 2022xkq, an underluminous fast-declining type Ia supernova (SN Ia) in NGC 1784 ($\mathrm{D}\approx31$ Mpc), from $<1$ to 180 days after explosion. The high-cadence observations of SN 2022xkq, a photometrically transitional and spectroscopically 91bg-like SN Ia, cover the first days and weeks following explosion which are critical to distinguishing between explosion scenarios. The early light curve of SN 2022xkq has a red early color and exhibits a flux excess which is more prominent in redder bands; this is the first time such a feature has been seen in a transitional/91bg-like SN Ia. We also present 92 optical and 19 near-infrared (NIR) spectra, beginning 0.4 days after explosion in the optical and 2.6 days after explosion in the NIR. SN 2022xkq exhibits a long-lived C I 1.0693 $\mu$m feature which persists until 5 days post-maximum. We also detect C II $\lambda$6580 in the pre-maximum optical spectra. These lines are evidence for unburnt carbon that is difficult to reconcile with the double detonation of a sub-Chandrasekhar mass white dwarf. No existing explosion model can fully explain the photometric and spectroscopic dataset of SN 2022xkq, but the considerable breadth of the observations is ideal for furthering our understanding of the processes which produce faint SNe Ia.Comment: 38 pages, 16 figures, accepted for publication in ApJ, the figure 15 input models and synthetic spectra are now available at https://zenodo.org/record/837925

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions