Heat shock proteins Hsp27 and Hsp32 localize to synaptic sites in the rat cerebellum following hyperthermia

Stressful stimuli activate the heat shock (stress) response in which a set of heat shock proteins (hsps) is induced, which play roles in cellular repair and protective mechanisms. Most studies in the mammalian nervous system have focused on Hsp70, however, the present investigation targets other members of the induced set, namely Hsp27 and Hsp32. In response to hyperthermia, these hsps are strongly induced in Bergmann glial cells in the rat brain and transported into their radial fibers, which project into the `synaptic-enriched' molecular layer of the cerebellum. Using subcellular fractionation and immunoelectron microscopy, hyperthermia-induced Hsp27 and Hsp32 were detected in synaptic elements and in perisynaptic glial processes. These results suggest that stress-induced Hsp27 and Hsp32 may contribute to repair and protective mechanisms at the synapse

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis

Suprachiasmatic nucleus-dependent and independent outputs driving rhythmic activity in hypothalamic and thalamic neurons

From Springer Nature via Jisc Publications RouterHistory: received 2020-05-29, registration 2020-09-17, accepted 2020-09-17, pub-electronic 2020-09-30, online 2020-09-30, collection 2020-12Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/N007115/1Abstract: Background: Daily variations in mammalian physiology are under control of a central clock in the suprachiasmatic nucleus (SCN). SCN timing signals are essential for coordinating cellular clocks and associated circadian variations in cell and tissue function across the body; however, direct SCN projections primarily target a restricted set of hypothalamic and thalamic nuclei involved in physiological and behavioural control. The role of the SCN in driving rhythmic activity in these targets remains largely unclear. Here, we address this issue via multielectrode recording and manipulations of SCN output in adult mouse brain slices. Results: Electrical stimulation identifies cells across the midline hypothalamus and ventral thalamus that receive inhibitory input from the SCN and/or excitatory input from the retina. Optogenetic manipulations confirm that SCN outputs arise from both VIP and, more frequently, non-VIP expressing cells and that both SCN and retinal projections almost exclusively target GABAergic downstream neurons. The majority of midline hypothalamic and ventral thalamic neurons exhibit circadian variation in firing and those receiving inhibitory SCN projections consistently exhibit peak activity during epochs when SCN output is low. Physical removal of the SCN confirms that neuronal rhythms in ~ 20% of the recorded neurons rely on central clock input but also reveals many neurons that can express circadian variation in firing independent of any SCN input. Conclusions: We identify cell populations across the midline hypothalamus and ventral thalamus exhibiting SCN-dependent and independent rhythms in neural activity, providing new insight into the mechanisms by which the circadian system generates daily physiological rhythms

A deep Large Binocular Telescope view of the Canes Venatici I dwarf galaxy

We present the first deep color-magnitude diagram of the Canes Venatici I (CVnI) dwarf galaxy from observations with the wide field Large Binocular Camera on the Large Binocular Telescope. Reaching down to the main-sequence turnoff of the oldest stars, it reveals a dichotomy in the stellar populations of CVnI: it harbors an old (> 10 Gyr), metal-poor ([Fe/H] ~ -2.0) and spatially extended population along with a much younger (~ 1.4-2.0 Gyr), 0.5 dex more metal-rich, and spatially more concentrated population. These young stars are also offset by 64_{-20}^{+40} pc to the East of the galaxy center. The data suggest that this young population, which represent ~ 3-5 % of the stellar mass of the galaxy within its half-light radius, should be identified with the kinematically cold stellar component found by Ibata et al. (2006). CVnI therefore follows the behavior of the other remote MW dwarf spheroidals which all contain intermediate age and/or young populations: a complex star formation history is possible in extremely low-mass galaxies.Comment: 4 pages, 3 figures, accepted for publication in ApJL. Minor changes, conclusions unchange

Sleep and cognitive performance:cross-sectional associations from the UK Biobank

Objective: The relationship between insomnia symptoms and cognitive performance is unclear, particularly at the population level. We conducted the largest examination of this association to date through analysis of the UK Biobank, a large population-based sample of adults aged 40-69 yrs. We also sought to determine associations between cognitive performance and self-reported chronotype, sleep medication use, and sleep duration. Methods: This cross-sectional, population-based study involved 477,529 participants, comprising 133,314 with frequent insomnia symptoms (age: 57.4 ± 7.7 yrs; 62.1% female) and 344,215 controls without (age: 56.1 ± 8.2 yrs; 52.0% female). Cognitive performance was assessed through a touchscreen test battery probing reasoning, basic reaction time, numeric memory, visual memory and prospective memory. Adjusted models included relevant demographic, clinical and sleep variables. Results: Frequent insomnia symptoms were associated with cognitive impairment in unadjusted models, however these effects were reversed after full adjustment, leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without. Relative to intermediate chronotype, evening chronotype was associated with superior task performance, while morning chronotype was associated with the poorest performance. Sleep medication use and both long (>9hrs) and short (<7hrs) sleep duration were associated with impaired performance. Conclusions: Our results suggest that after adjustment for potential confounding variables, frequent insomnia symptoms may be associated with a small statistical advantage, which is unlikely to be clinically meaningful, on simple neurocognitive tasks. Further work is required to examine mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance, as well as impairment associated with morning chronotype, sleep medication use, and sleep duration extremes

Molecular Hydrogen in the Damped Ly alpha Absorber of Q1331+170

We used HST/STIS to obtain the spectrum of molecular hydrogen associated with the damped Ly$\alpha$ system at $z_{\rm abs}=1.7765$ toward the quasar Q1331+170 at $z_{\rm em}=2.084$. Strong ${\rm H}_2$ absorption was detected, with a total ${\rm H}_2$ column density of $N({\rm H}_2)=(4.45\pm 0.36)\times 10^{19} {\rm cm^{-2}}$.The molecular hydrogen fraction is $f_{{\rm H}_2}=\frac{2N_{\rm H_2}}{N_{\rm HI}+2N_{\rm H_2}}=(5.6\pm 0.7)$, which is the greatest value reported so far in any redshifted damped Ly$\alpha$ system. This results from the combined effect of a relatively high dust-to-gas ratio, a low gas temperature, and an extremely low ambient UV radiation field. Based on the observed population of $J$ states, we estimate the photo-absorption rate to be $R_{\rm abs}=(7.6\pm 2.4)\times 10^{-13} {\rm s^{-1}}$, corresponding to a local UV radiation field of $J(1000{\rm \AA})\approx 2.1\times 10^{-3} J_{1000{\rm \AA},\odot}$, where $J_{1000{\rm \AA},\odot}$ is the UV intensity at $1000 \AA$ in the solar neighborhood. This is comparable with the metagalactic UV background intensity at this redshift, and implies an extremely low star formation rate in the absorber's environment. The observed CO-to-H$_2$ column density ratio is $\frac{N_{\rm CO}}{N_{\rm H_2}}<2.5\times 10^{-7}$, which is similar to the value measured for diffuse molecular clouds in the Galactic ISM. Finally, applying the inferred physical conditions to the observed C I fine structure excitation (Songaila {\it et al.} 1994), we estimate the cosmic microwave background temperature to be $T_{\rm CMB}=(7.2\pm 0.8) {\rm K}$ at $z=1.77654$, consistent with the predicted value of $7.566 {\rm K}$ from the standard cosmology.Comment: Accepted for publication, Astrophysical Journal. Abstract abbreviate

Pressure Support vs. Thermal Broadening in the Lyman-alpha Forest II: Effects of the Equation of State on Transverse Structure

We examine the impact of gas pressure on the transverse coherence of high-redshift (2 <= z <= 4) Lyman-alpha forest absorption along neighboring lines of sight that probe the gas Jeans scale (projected separation Delta r <= 500 kpc/h comoving; angular separation Delta theta <= 30"). We compare predictions from two smoothed particle hydrodynamics (SPH) simulations that have different photoionization heating rates and thus different temperature-density relations in the intergalactic medium (IGM). We also compare spectra computed from the gas distributions to those computed from the pressureless dark matter. The coherence along neighboring sightlines is markedly higher for the hotter, higher pressure simulation, and lower for the dark matter spectra. We quantify this coherence using the flux cross-correlation function and the conditional distribution of flux decrements as a function of transverse and line-of-sight (velocity) separation. Sightlines separated by Delta theta <= 15" are ideal for probing this transverse coherence. Higher pressure decreases the redshift-space anisotropy of the flux correlation function, while higher thermal broadening increases the anisotropy. In contrast to the longitudinal (line-of-sight) structure of the Lya forest, the transverse structure on these scales is dominated by pressure effects rather than thermal broadening. With the rapid recent growth in the number of known close quasar pairs, paired line-of-sight observations offer a promising new route to probe the IGM temperature-density relation and test the unexpectedly high temperatures that have been inferred from single sightline analyses.Comment: 11 figures, submitted to MNRA

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment