Evidence for Time-of-Day Dependent Effect of Neurotoxic Dorsomedial Hypothalamic Lesions on Food Anticipatory Circadian Rhythms in Rats

The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (Tb) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and Tb rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and Tb rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep

Establishing the baseline level of repetitive element expression in the human cortex

Background: Although nearly half of the human genome is comprised of repetitive sequences, the expression profile of these elements remains largely uncharacterized. Recently developed high throughput sequencing technologies provide us with a powerful new set of tools to study repeat elements. Hence, we performed whole transcriptome sequencing to investigate the expression of repetitive elements in human frontal cortex using postmortem tissue obtained from the Stanley Medical Research Institute. Results: We found a significant amount of reads from the human frontal cortex originate from repeat elements. We also noticed that Alu elements were expressed at levels higher than expected by random or background transcription. In contrast, L1 elements were expressed at lower than expected amounts. Conclusions: Repetitive elements are expressed abundantly in the human brain. This expression pattern appears to be element specific and can not be explained by random or background transcription. These results demonstrate that our knowledge about repetitive elements is far from complete. Further characterization is required to determine the mechanism, the control, and the effects of repeat element expression

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Enhanced Food Anticipatory Activity Associated with Enhanced Activation of Extrahypothalamic Neural Pathways in Serotonin2C Receptor Null Mutant Mice

The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin2C receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

Support to the public services mutation through continuous improvement in a french metropolis

Public Services have their own principles and codes in order to address needs of general interest through the procurement of physical objects, information or services to various kinds of users. Characterized by a political context and a dedicated legal framework, public services have specific constraints and objectives. This communication shows how continuous improvement methods born in an industrial context could be adapted for addressing the specificity of public service, especially in the new context of "Smart Cities"

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities

Reactive oxygen species and small-conductance calcium-dependent potassium channels are key mediators of inflammation-induced hypotension and shock

Septic shock is associated with life-threatening vasodilation and hypotension. To cause vasodilation, vascular endothelium may release nitric oxide (NO), prostacyclin (PGI2), and the elusive endothelium-derived hyperpolarizing factor (EDHF). Although NO is critical in controlling vascular tone, inhibiting NO in septic shock does not improve outcome, on the contrary, precipitating the search for alternative therapeutic targets. Using a hyperacute tumor necrosis factor (TNF)-induced shock model in mice, we found that shock can develop independently of the known vasodilators NO, cGMP, PGI2, or epoxyeicosatrienoic acids. However, the antioxidant tempol efficiently prevented hypotension, bradycardia, hypothermia, and mortality, indicating the decisive involvement of reactive oxygen species (ROS) in these phenomena. Also, in classical TNF or lipopolysaccharide-induced shock models, tempol protected significantly. Experiments with (cell-permeable) superoxide dismutase or catalase, N-acetylcysteine and apocynin suggest that the ROS-dependent shock depends on intracellular \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^\bullet {\hbox{OH}}$$\end{document} radicals. Potassium channels activated by ATP (KATP) or calcium (KCa) are important mediators of vascular relaxation. While NO and PGI2-induced vasodilation involves KATP and large-conductance BKCa channels, small-conductance SKCa channels mediate vasodilation induced by EDHF. Interestingly, also SKCa inhibition completely prevented the ROS-dependent shock. Our data thus indicate that intracellular \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^\bullet {\hbox{OH}}$$\end{document} and SKCa channels represent interesting new therapeutic targets for inflammatory shock. Moreover, they may also explain why antioxidants other than tempol fail to provide survival benefit during shock

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012