Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Measurements of the UV background at 4.6 < z < 6.4 using the quasar proximity effect

We present measurements of the ionising ultraviolet background (UVB) at z ~ 5-6 using the quasar proximity effect. The fifteen quasars in our sample cover the range 4.6 < z_q < 6.4, enabling the first proximity effect measurements of the UVB at z > 5. The metagalactic hydrogen ionisation rate, Gamma_bkg, was determined by modelling the combined ionisation field from the quasar and the UVB in the proximity zone on a pixel-by-pixel basis. The optical depths in the spectra were corrected for the expected effect of the quasar until the mean flux in the proximity region equalled that in the average Ly-alpha forest, and from this we make a measurement of Gamma_bkg. A number of systematic effects were tested using synthetic spectra. Noise in the flux was found to be the largest source of bias at z ~ 5, while uncertainties in the mean transmitted Ly-alpha flux are responsible for the largest bias at z ~ 6. The impacts of large-scale overdensities and Lyman limit systems on Gamma_bkg were also investigated, but found to be small at z > 5. We find a decline in Gamma_bkg with redshift, from log(Gamma_bkg) = -12.15 $\pm$ 0.16 at z ~ 5 to log(Gamma_bkg) = -12.84 $\pm$ 0.18 at z ~ 6 (1 sigma errors). Compared to UVB measurements at lower redshifts, our measurements suggest a drop of a factor of five in the HI photoionisation rate between z ~ 4 and z ~ 6. The decline of Gamma_bkg appears to be gradual, and we find no evidence for a sudden change in the UVB at any redshift that would indicate a rapid change in the attenuation length of ionising photons. Combined with recent measurements of the evolution of the mean free path of ionising photons, our results imply decline in the emissivity of ionising photons by roughly a factor of two from z ~ 5 to 6, albeit with significant uncertainty due to the measurement errors in both Gamma_bkg and the mean free path.Comment: 22 pages, 19 figures, 5 tables; accepted for publication in MNRA

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system

Multi-model evaluation of the sensitivity of the global energy budget and hydrological cycle to resolution

This study undertakes a multi-model comparison with the aim to describe and quantify systematic changes of the global energy and water budgets when the horizontal resolution of atmospheric models is increased and to identify common factors of these changes among models. To do so, we analyse an ensemble of twelve atmosphere-only and six coupled GCMs, with different model formulations and with resolutions spanning those of state-of-the-art coupled GCMs, i.e. from resolutions coarser than 100 km to resolutions finer than 25 km. The main changes in the global energy budget with resolution are a systematic increase in outgoing longwave radiation and decrease in outgoing shortwave radiation due to changes in cloud properties, and a systematic increase in surface latent heat flux; when resolution is increased from 100 to 25 km, the magnitude of the change of those fluxes can be as large as 5 W m−2. Moreover, all but one atmosphere-only model simulate a decrease of the poleward energy transport at higher resolution, mainly explained by a reduction of the equator-to-pole tropospheric temperature gradient. Regarding hydrological processes, our results are the following: (1) there is an increase of global precipitation with increasing resolution in all models (up to 40 × 103 km3 year−1) but the partitioning between land and ocean varies among models; (2) the fraction of total precipitation that falls on land is on average 10% larger at higher resolution in grid point models, but it is smaller at higher resolution in spectral models; (3) grid points models simulate an increase of the fraction of land precipitation due to moisture convergence twice as large as in spectral models; (4) grid point models, which have a better resolved orography, show an increase of orographic precipitation of up to 13 × 103 km3 year−1 which explains most of the change in land precipitation; (5) at the regional scale, precipitation pattern and amplitude are improved with increased resolution due to a better simulated seasonal mean circulation. We discuss our results against several observational estimates of the Earth's energy budget and hydrological cycle and show that they support recent high estimates of global precipitation

É possível ensinar inglês com música? Uma reflexão sobre música e aprendizagem

O presente texto é resultado das pesquisas de três professores que atuam na educação básica em nível municipal e estadual dentro do estado de Santa Catarina. Neste caso, os referidos professores são estudantes do mestrado profissional em educação básica do PPGEB/UNIARP e são orientados pelo mesmo profissional. Assim, as linhas que se delineiam a seguir são decorrentes de estratégias de ensino que visam a extrapolar os métodos tradicionais e bancários de ensino da língua inglesa. A ideia de motivar os alunos por meio da música não é uma regra nem privilégio dos professores do idioma inglês, mas é uma metodologia aceitável para o desenvolvimento da capacidade de aprendizado que os alunos podem ter ao aproximar o mundo cotidiano do mundo do ensino nas salas de aula. Assim, a metodologia deste trabalho é de ordem bibliográfica e se alicerça na necessidade de criar novos meios de ensino para estudantes do ensino fundamental e médio, principalmente após a pandemia da Covid-19. As considerações finais apresentam os possíveis desdobramentos que este trabalho pode atingir na medida em que as possibilidades de ensino-aprendizagem do inglês se tornam inovadoras e transformadoras, superando a tradicional hierarquia professor-aluno por meio de uma parceria entre docentes e discentes no sentido de que a motivação é o carro-chefe do ensino numa perspectiva colaborativa e inclusiva

Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism

The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. Using antibody-independent ChIP-sequencing of REVERBα in mouse liver, we reveal a high-confidence cistrome and define direct target genes. REVERBα-binding sites are highly enriched for consensus RORE or RevDR2 motifs and overlap with corepressor complex binding. We find no evidence for transcription factor tethering and DNA-binding domain-independent action. Moreover, hepatocyte-specific deletion of Reverbα drives only modest physiological and transcriptional dysregulation, with derepressed target gene enrichment limited to circadian processes. Thus, contrary to previous reports, hepatic REVERBα does not repress lipogenesis under basal conditions. REVERBα control of a more extensive transcriptional program is only revealed under conditions of metabolic perturbation (including mistimed feeding, which is a feature of the global Reverbα -/- mouse). Repressive action of REVERBα in the liver therefore serves to buffer against metabolic challenge, rather than drive basal rhythmicity in metabolic activity

Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

SignificanceRheumatoid arthritis (RA) is a debilitating chronic inflammatory disease in which symptoms exhibit a strong time-of-day rhythmicity. RA is commonly associated with metabolic disturbance and increased incidence of diabetes and cardiovascular disease, yet the mechanisms underlying this metabolic dysregulation remain unclear. Here, we demonstrate that rhythmic inflammation drives reorganization of metabolic programs in distal liver and muscle tissues. Chronic inflammation leads to mitochondrial dysfunction and dysregulation of fatty acid metabolism, including accumulation of inflammation-associated ceramide species in a time-of-day-dependent manner. These findings reveal multiple points for therapeutic intervention centered on the circadian clock, metabolic dysregulation, and inflammatory signaling

PRÁTICAS PEDAGÓGICAS PARA O ENSINO DE INGLÊS: TRANSCULTURALIDADE, MÚSICA E ABORDAGEM ORIENTADA À AÇÃO COMO ESTRATÉGIAS DE TRABALHO COM ESTUDANTES DA EDUCAÇÃO BÁSICA: PEDAGOGICAL PRACTICES FOR TEACHING ENGLISH: CROSS-CULTURALITY, MUSIC AND ACTION-ORIENTED APPROACHES AS WORKING STRATEGIES WITH BASIC EDUCATION STUDENTS

This article succinctly presents the results of three master's research projects from the Graduate Program in Basic Education at UNIARP, Caçador-SC, focused on activities to motivate elementary and high school students in learning English. The research emphasizes the need to make the teaching of the language more relevant, considering the challenges of motivating students to understand the purpose of learning the language. Therefore, the proposed strategies aimed to connect English with daily life, recognizing its importance as a global language. All activities were developed in collaboration with the students. The article is divided into three parts: 1) Transculturality in High School Education: explores how learning English can open doors to other cultures and develop cultural awareness, using films for this purpose; 2) Music in Elementary Education: highlights the use of music as a motivational and facilitative tool for learning English, with creative strategies to address language skills; 3) Action-Oriented Approach (AoA): proposes a task-based approach, comparing CEFR and BNCC skills to improve English teaching, suggesting more time and suitable materials. Additionally, a travel website was created in partnership with students based on AoA. Overall, the dissertations emphasize the importance of finding innovative ways to inspire students in the study of the English language. The research methodology was based on the bibliographic format and the practice of action research. The goal is to inspire further research and the creation of relevant educational materials to enhance the teaching of this language.O presente artigo apresenta, de modo sucinto, o resultado de três pesquisas de mestrado do Programa de Pós-Graduação em Educação Básica da UNIARP, de Caçador-SC, focadas em atividades para motivar estudantes do Ensino Fundamental e Médio no aprendizado do idioma inglês. As pesquisas enfatizam a necessidade de tornar o ensino do idioma mais relevante, considerando os desafios de motivar os estudantes a compreenderem o sentido do aprendizado do referido idioma. Diante disso, as estratégias propostas buscaram conectar o inglês com a vida cotidiana, reconhecendo sua importância como língua global. Todas as atividades foram desenvolvidas em colaboração com os estudantes. O artigo se divide em três partes: 1) Transculturalidade no Ensino Médio: explora como aprender inglês pode abrir portas para outras culturas e desenvolver consciência cultural, usando filmes para isso; 2) Música no Ensino Fundamental: destaca o uso da música como ferramenta motivacional e facilitadora do aprendizado de inglês, com estratégias criativas para abordar habilidades linguísticas e 3) Abordagem Orientada a Ação (AoA): propõe uma abordagem baseada em tarefas, comparando habilidades do CEFR e BNCC para estudantes melhorar o ensino do inglês, sugerindo mais tempo e materiais adequados. Além disso, foi criado em parceria com os estudantes um site de viagens com base na AoA. No geral, as dissertações ressaltam a importância de encontrar formas inovadoras de instigar os estudantes no estudo do idioma inglês. A metodologia da pesquisa se pautou no formato bibliográfico e na prática da pesquisa-ação. O objetivo é inspirar mais pesquisas e a criação de materiais educacionais relevantes para aprimorar o ensino desse idioma. Palavras-chave: Educação Básica, Ensino de Inglês, Motivação, Estratégias Pedagógicas, Integração Curricular  Abstract This article succinctly presents the results of three master's research projects from the Graduate Program in Basic Education at UNIARP, Caçador-SC, focused on activities to motivate elementary and high school students in learning English. The research emphasizes the need to make the teaching of the language more relevant, considering the challenges of motivating students to understand the purpose of learning the language. Therefore, the proposed strategies aimed to connect English with daily life, recognizing its importance as a global language. All activities were developed in collaboration with the students. The article is divided into three parts: 1) Transculturality in High School Education: explores how learning English can open doors to other cultures and develop cultural awareness, using films for this purpose; 2) Music in Elementary Education: highlights the use of music as a motivational and facilitative tool for learning English, with creative strategies to address language skills; 3) Action-Oriented Approach (AoA): proposes a task-based approach, comparing CEFR and BNCC skills to improve English teaching, suggesting more time and suitable materials. Additionally, a travel website was created in partnership with students based on AoA. Overall, the dissertations emphasize the importance of finding innovative ways to inspire students in the study of the English language. The research methodology was based on the bibliographic format and the practice of action research. The goal is to inspire further research and the creation of relevant educational materials to enhance the teaching of this language. Keywords: Basic Education, English Teaching, Motivation, Pedagogical Strategies, Curricular Integration