Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with periodicity of about day, these use molecular oscillators consisting two interlocked feedback loops. The core loop generates by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas stabilizing establishes roughly antiphasic nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism physiology. Here we show...

Most behavioral experiments within circadian research are based on the analysis of locomotor activity. This paper introduces scientists to chronobiology by explaining basic terminology used field. Furthermore, it aims assist in designing, carrying out, and evaluating wheel-running with rodents, particularly mice. Since light is an easily applicable stimulus that provokes strong effects clock phase, focuses application different lighting conditions.

Daily patterns of animal behavior are potentially vast functional importance. Fitness benefits have been identified in nature by the association between individual timing and survival or fate individuals after experimental deletion their circadian pacemaker. The recent advances unraveling molecular basis enable new approaches to natural selection on timing. investigators report effect mutant Per2 Brdm1 allele 4 replicate populations house mice a seminatural outside environment over 2 years....

The function of the nuclear receptor Rev-erbα (Nr1d1) in brain is, apart from its role circadian clock mechanism, unknown. Therefore, we compared gene expression profiles between wild-type and knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target repression by REV-ERBα. Loss manifested memory mood related behavioral phenotypes led to overexpression Fabp7 various areas including subgranular zone (SGZ) hippocampus, where neuronal progenitor cells...

Background Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated various physiological processes, including bone formation. Osteoblasts build new mineralized whereas osteoclasts degrade it thereby balancing To evaluate the contribution of clock components this process, we investigated mice mutant for a volume phenotype. Methodology/Principal Findings We found that Per2Brdm1 as well lacking Cry2−/− displayed significantly increased at 12...

Within the suprachiasmatic nucleus (SCN) of hypothalamus, circadian timekeeping and resetting have been shown to be largely dependent on both membrane depolarization intracellular second-messenger signaling. In these processes, voltage-gated calcium channels (VGCCs) mediate voltage-dependent influx, which propagates neural impulses by stimulating vesicle fusion instigates pathways resulting in clock gene expression. Through cumulative actions phase internal is modified match light cycle...

Telomere shortening is a presumed tumor suppressor pathway that imposes proliferative barrier (the Hayflick limit) during tumorigenesis. This model predicts excessively long somatic telomeres predispose to cancer. Here, we describe cancer-prone families with two unique TINF2 mutations truncate TIN2, shelterin subunit controls telomere length. Patient lymphocyte were unusually long. We show the truncated TIN2 proteins do not localize telomeres, suggesting create loss-of-function alleles....

Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set clock genes generate maintain these rhythms with period about 24 hours. Many proteins undergo circadian cycles modifications. Among modifications, protein phosphorylation plays an role in regulating activity, stability intracellular localization components. Several kinases were characterized as regulators clock. However, function...

Period2 (Per2) is an important component of the circadian clock. Mutation this gene associated with vascular endothelial dysfunction and altered glucose metabolism. The aim study to further characterize whole body homeostasis nitric oxide (NO) production in response insulin mPer2(Brdm1) mice. We show that mice exhibit compromised receptor activation Akt signaling various tissues including liver, fat, heart, aortas a tissue-specific heterogeneous diurnal pattern, decreased insulin-stimulated...

Neurotransmitters are concentrated into synaptic vesicles by VGLUT (vesicular glutamate transporter) or VGAT GABA transporter). The number of VGLUTs per vesicle determines the amount stored neurotransmitter, thereby influencing postsynaptic response. Recently, we described a strong diurnal cycling VGLUT1 on prepared from whole mouse brain at different times day (Yelamanchili, S. V., Pendyala, G., Brunk, I., Darna, M., Albrecht, U., and Ahnert-Hilger, G. (2006) J. Biol. Chem. 281,...

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants at least 13 genes underlie different forms of NCL, almost all which recessively inherited. To date 8 canine orthologs human NCL have been found to occur 11 dog breeds they result similar NCLs. Canine NCLs can serve as models for preclinical evaluation therapeutic interventions these disorders. In most...

A strong stimulus adjusting the circadian clock to prevailing light-dark cycle is light. However, reset by light only at specific times of day. The mechanisms mediating such gating input CNS are not well understood. There evidence that Ca(2+) ions play an important role in intracellular signaling mechanisms, including cascades stimulated Therefore, hypothesized a light-mediated resetting clock. Calbindin-D28k (CB; gene symbol: Calb1) binding protein implicated homeostasis and sensing....

The recurring light/dark cycle that has a period length of about 24 hours been internalized in various organisms the form circadian clock. This clock allows precise orchestration biochemical and physiological processes body thus improving performance. Recently, we found component PERIOD2 (PER2) can coordinate transcriptional regulation metabolic, physiological, or behavioral pathways by interacting with nuclear receptors. PER2 appears to act as co-regulator receptors linking function at...

We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures ventral strabismus consistent with diffuse intracranial lesion. Magnetic resonance imaging revealed white matter disease without mass effect. Macroscopically, the cerebral showed gelatinous texture centrum...

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A fractious nine-year-old, 520-kg, neutered Swiss Warmblood was presented with a history of anorexia, progressive weight loss and mild hindlimb lameness. Because its temperament, standard physical examination considered to be only feasible under general anaesthesia. For safety reasons, anaesthesia planned induced by blowpipe darting. Two attempts are described discussed in the present report. The first attempt, using combination medetomidine tiletamine-zolazepam, unsuccessful. Conversely,...

This protocol is for nuclei isolation from frozen mouse brain or human postmortem and processing of these loading on single cell sequencing platforms. Nuclei are prepared by dounce homogenization under mild lysis conditions. They purified myelin, subcellular debris ambient RNA using centrifugation through an iodixanol cushion. Isolated can be directly loaded onto a nucleus platform they additionally permeabilized combined RNAseq/ATACseq. The compatible with working small amounts tissue,...