Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock

Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K+ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain

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

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

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

Electrospun natural rubber fibers-based flexible conductive membranes

In recent years, the technique of electrospinning has been used to develop a novel class of micro- and nanoscale materials based on fibrous structures. Several polymers, in particular elastomers, that have been implemented in this process rely on properties such as elasticity, flexibility, biocompatibility, and low cost. Herein, we describe for the first time the electrospinning of natural rubber fibers without polymeric matrix to obtain self-standing non-woven mats and oriented elastomeric fibers. The fibers average diameters were approximately 5.5 µm. Polyaniline (PAni) was deposited on the membrane surface in order to enhance the conductive properties making easy the charge transportation. We have obtained biocompatible and flexible fibrous materials using natural rubber, this research opens up possibilities of using micro and nanofibers of only-natural rubber in many applications including sensors preparation. Keywords: Electrospinning; Fiber technology; Microstructure; Polymer; Sensors

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

High-Dimensional Coexistence of Temperate Tree Species: Functional Traits, Demographic Rates, Life-History Stages, and Their Physical Context

Theoretical models indicate that trade-offs between growth and survival strategies of tree species can lead to coexistence across life history stages (ontogeny) and physical conditions experienced by individuals. There exist predicted physiological mechanisms regulating these trade-offs, such as an investment in leaf characters that may increase survival in stressful environments at the expense of investment in bole or root growth. Confirming these mechanisms, however, requires that potential environmental, ontogenetic, and trait influences are analyzed together. Here, we infer growth and mortality of tree species given size, site, and light characteristics from forest inventory data from Wisconsin to test hypotheses about growth-survival trade-offs given species functional trait values under different ontogenetic and environmental states. A series of regression analyses including traits and rates their interactions with environmental and ontogenetic stages supported the relationships between traits and vital rates expected from the expectations from tree physiology. A combined model including interactions between all variables indicated that relationships between demographic rates and functional traits supports growth-survival trade-offs and their differences across species in high-dimensional niche space. The combined model explained 65% of the variation in tree growth and supports a concept of community coexistence similar to Hutchinson's n-dimensional hypervolume and not a low-dimensional niche model or neutral model