High-resolution analysis of individual Drosophila melanogaster larvae uncovers individual variability in locomotion and its neurogenetic modulation

Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its simple brain and genetic accessibility, the larva of the fruit fly Drosophila melanogaster allows one to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual, most studies of locomotion in larvae use measurements aggregated across animals, or animals tested one by one, an extravagance for larger-scale analyses. This prevents grasping the inter- and intra-individual variability in locomotion and its neurogenetic determinants. Here, we present the IMBA (individual maggot behaviour analyser) for analysing the behaviour of individual larvae within groups, reliably resolving individual identity across collisions. We use the IMBA to systematically describe the inter- and intra-individual variability in locomotion of wild-type animals, and how the variability is reduced by associative learning. We then report a novel locomotion phenotype of an adhesion GPCR mutant. We further investigated the modulation of locomotion across repeated activations of dopamine neurons in individual animals, and the transient backward locomotion induced by brief optogenetic activation of the brain-descending ‘mooncrawler’ neurons. In summary, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and its variability of individual larvae, with utility in multiple biomedical research contexts

Consumo de alimentos ultraprocessados e o risco de mortalidade: uma revisão sistemática

ABSTRACT Introduction and Objectives: Ultra-processed foods are determined by the level of processing. There has been a relationship between their consumption and several risk factors for diseases related to these foods, such as cardiovascular disease. These factors can corroborate the illness and increase the risk of mortality of the adult population. The objective of this systematic review was to verify the contribution of the consumption of ultra-processed foods to the risk of mortality. Methods: Through PubMed, Scopus and Web of Science, scientific databases, studies that examine the relationship between the consumption of ultra-processed foods and the risk of mortality up to February 2021 were systematically researched. Results and Conclusion: Evidence analysis was performed using robust tools to assess the risk of bias and methodological quality. A total of five studies were included. The consumption of ultra-processed foods was associated with a higher risk of mortality from all causes, proportional to their consumption (in the largest quartiles of consumption, greater risks were found).Introdução e objetivos: Alimentos ultraprocessados ​​são determinados pelo nível de processamento. Existe uma relação entre seu consumo e diversos fatores de risco para doenças relacionadas a esses alimentos, como as cardiovasculares. Esses fatores podem corroborar o adoecimento e aumentar o risco de mortalidade da população adulta. O objetivo desta revisão sistemática foi verificar a contribuição do consumo de alimentos ultraprocessados ​​e o risco de mortalidade. Métodos: Por meio do PubMed, Scopus e Web of Science, foram pesquisadas ​​sistematicamente em tais bases de dados científicas, estudos que examinam a relação entre o consumo de alimentos ultraprocessados ​​e o risco de mortalidade até fevereiro de 2021. Resultados e Conclusão: A análise de evidências foi realizada por meio de ferramentas robustas para avaliar o risco de viés e a qualidade metodológica. Um total de cinco estudos foram incluídos. O consumo de alimentos ultraprocessados ​​foi associado a um maior risco de mortalidade por todas as causas, proporcional ao seu consumo (nos maiores quartis de consumo, foram encontrados maiores riscos). Palavras-chave: Alimentos Ultraprocessados, Consumo de Alimentos, Mortalidade, Revisão Sistemática

MAPEAMENTO DAS CARACTERÍSTICAS DO PROTOCOLO TCP EXPLORADA POR ATAQUES DDoS

Com a expansão e a democratização do acesso à tecnologia nas últimas décadas, a Internet e os serviços de comunicação se tornaram alvos cada vez mais comuns de atividades maliciosas. O número de dispositivos e serviços vulneráveis a ataques cibernéticos cresce de maneira exponencial, graças a ascensão dos meios de comunicação e da rede IoT, sendo necessária a compreensão dos mecanismos e vetores empreendidos nessas violações para tornar as redes mais seguras. Nesse sentido, os Ataques Distribuídos de Negação de Serviços (DDoS), ganharam notoriedade na sociedade devido à agressividade e aos danos causados por esses ataques quando bem sucedidos, assim como pela variabilidade de métodos. Esses ataques podem explorar diversas especificidades e vulnerabilidades dos protocolos de comunicação de rede - em especial do protocolo TCP, atuante na camada de transporte, que é utilizado para a transmissão de informações na internet - com a finalidade de comprometer e/ou interromper os serviços disponibilizados pelo alvo e intermediários. Inicialmente, a internet foi elaborada para ser funcional e oferecer desempenho no atendimento a necessidade de interconexão entre dispositivos, o que tornou a segurança na sua criação e construção um elemento secundário. Os problemas de segurança envolvendo redes de computadores e a internet só começaram a aparecer significativamente décadas depois, quando era tarde demais para repensar os protocolos que já eram utilizados em larga escala. O principal exemplo é o conjunto de protocolos TCP/IP que assume que todos os usuários conectados não têm nenhuma intenção maliciosa, o que não se reverbera com ênfase quando se analisa o cenário de usuários atual. Dessa forma, essa pesquisa buscou mapear as características do protocolo TCP que são exploradas para a realização de ataques DDoS, devido a sua importância no contexto da intercomunicação e a recorrência com a qual o protocolo é utilizado. Para a obtenção desse conhecimento, foram realizadas, ao longo do ano, pesquisas bibliográficas, em teóricos da ciência da computação com ênfase em redes de computadores, assim como em artigos científicos, junto a experimentos empíricos em ambiente controlado, utilizando máquinas virtuais como Linux e Metasploitable, a fim de consolidar e embasar a base teórica para a diferenciação desses fenômenos tecnológicos. Assim, este estudo foi capaz de identificar três principais variações dos Ataques DDoS TCP: TCP ACK, TCP SYN E TCP SYN-ACK, todos incidentes na etapa de estabelecimento de conexão do protocolo entre duas máquinas, conhecido como Three-Way-Handshake, que visa garantir a inicialização da transmissão de dados. A diferenciação entre os três tipos de ataque ocorreu pela análise de três fatores principais: o alvo, a existência de intermediário (que acarreta na origem do pacote malicioso) e as flags presentes no pacote, a fim de se tornar possível, através da aferição desses parâmetros, a identificação do ataque ocorrido na rede. Ainda assim, existe a necessidade de expandir a pesquisa, identificando novos conjuntos de dados com a finalidade de evidenciar outras características dos ataques DDoS baseados na pilha de protocolos TCP/IP

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1-3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The Amazon Tall Tower Observatory (ATTO): Overview of pilot measurements on ecosystem ecology, meteorology, trace gases, and aerosols

The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site. © Author(s) 2015

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.[Background] As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited.[Objective] The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.[Methods] We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.[Results] We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.[Conclusions] Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.This project was funded by The Michael J. Fox Foundation (ID 15015.02)Peer reviewe