The circadian clock in the choroid plexus drives rhythms in multiple cellular processes under the control of the suprachiasmatic nucleus.

Choroid plexus (ChP), the brain structure primarily responsible for cerebrospinal fluid production, contains a robust circadian clock, whose role remains to be elucidated. The aim of our study was to [1] identify rhythmically controlled cellular processes in the mouse ChP and [2] assess the role and nature of signals derived from the master clock in the suprachiasmatic nuclei (SCN) that control ChP rhythms. To accomplish this goal, we used various mouse models (WT, mPer2, ChP-specific Bmal1 knockout) and combined multiple experimental approaches, including surgical lesion of the SCN (SCNx), time-resolved transcriptomics, and single cell luminescence microscopy.

Circadian clock in choroid plexus is resistant to immune challenge but dampens in response to chronodisruption.

The choroid plexus (ChP) in the brain ventricles has a major influence on brain homeostasis. In this study, we aimed to determine whether the circadian clock located in ChP is affected by chronodisruption caused by misalignment with the external light/dark cycle and/or inflammation. Adult mPer2 mice were maintained in the LD12:12 cycle or exposed to one of two models of chronic chronodisruption - constant light for 22-25 weeks (cLL) or 6-hour phase advances of the LD12:12 cycle repeated weekly for 12 weeks (cLD-shifts).

Lithium affects the circadian clock in the choroid plexus - A new role for an old mechanism.

Lithium is an effective mood stabilizer, but the mechanism of its therapeutic action is not well understood. We investigated the effect of lithium on the circadian clock located in the ventricle barrier complex containing the choroid plexus (CP), a part of the glymphatic system that influences gross brain function via the production of cerebrospinal fluid. The mPer2 mice were injected with lithium chloride (LiCl) or vehicle, and their effects on the clock gene Nr1d1 in CP were detected by RT qPCR.

Misaligned feeding schedule elicits divergent circadian reorganizations in endo- and exocrine pancreas clocks.

Misaligned feeding may lead to pancreatic insufficiency, however, whether and how it affects circadian clock in the exocrine pancreas is not known. We exposed rats to a reversed restricted feeding regimen (rRF) for 10 or 20 days and analyzed locomotor activity, daily profiles of hormone levels (insulin, glucagon, and corticosterone) in plasma, and clock gene expression in the liver and endocrine and exocrine pancreas. In addition, we monitored responses of the exocrine pancreatic clock in organotypic explants of mPer2 mice in real time to acetylcholine, insulin, and glucocorticoids.

Early rhythmicity in the fetal suprachiasmatic nuclei in response to maternal signals detected by omics approach.

The suprachiasmatic nuclei (SCN) of the hypothalamus harbor the central clock of the circadian system, which gradually matures during the perinatal period. In this study, time-resolved transcriptomic and proteomic approaches were used to describe fetal SCN tissue-level rhythms before rhythms in clock gene expression develop. Pregnant rats were maintained in constant darkness and had intact SCN, or their SCN were lesioned and behavioral rhythm was imposed by temporal restriction of food availability.

Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin Ligase .

Normal neurodevelopment requires precise expression of the key ubiquitin ligase gene . Comparing newly generated mouse models for downregulation (models of Angelman syndrome) vs. upregulation (models for autism), we find reciprocal effects of gene dosage on phenotypes associated with circadian rhythmicity, including the amount of locomotor activity.

Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors.

Acetylcholine is an important modulator of striatal activity, and it is vital to controlling striatal-dependent behaviors, including motor and cognitive functions. Despite this significance, the mechanisms determining how acetylcholine impacts striatal signaling are still not fully understood. In particular, little is known about the role of nAChRs expressed by striatal interneurons.

High Sensitivity of the Circadian Clock in the Hippocampal Dentate Gyrus to Glucocorticoid- and GSK3-Beta-Dependent Signals.

Aims: Circadian clocks in the hippocampus (HPC) align memory processing with appropriate time of day. Our study was aimed at ascertaining the specificity of glycogen synthase kinase 3-beta (GSK3β)- and glucocorticoid (GC)-dependent pathways in the entrainment of clocks in individual HPC regions, CA1-3, and dentate gyrus (DG).

Methods: The role of GCs was addressed in vivo by comparing the effects of adrenalectomy (ADX) and subsequent dexamethasone (DEX) supplementation on clock gene expression profiles (Per1, Per2, Nr1d1, and Bmal1).

Targeted modification of the Per2 clock gene alters circadian function in mPer2luciferase (mPer2Luc) mice.

Modification of the Per2 clock gene in mPer2Luc reporter mice significantly alters circadian function. Behavioral period in constant dark is lengthened, and dissociates into two distinct components in constant light. Rhythms exhibit increased bimodality, enhanced phase resetting to light pulses, and altered entrainment to scheduled feeding.

The Challenge of Human Psychology to Effective Management of the COVID-19 Pandemic.

When it comes to the nature of the COVID-19 pandemic and the effectiveness of measures against the disease, many citizens worldwide do not trust their governments or health authorities. This brief essay discusses several psychological mechanisms which, under certain conditions, lead people to ignore important sources of information and hinder effective management of the epidemic. The paper shows that understanding psychological mechanisms, such as information neglect, cognitive dissonance, psychological reactance, and, in general, the diversity of people's thinking styles, may help leaders design more effective government communications.

Challenging the Integrity of Rhythmic Maternal Signals Revealed Gene-Specific Responses in the Fetal Suprachiasmatic Nuclei.

During fetal stage, maternal circadian system sets the phase of the developing clock in the suprachiasmatic nuclei (SCN) via complex pathways. We addressed the issue of how impaired maternal signaling due to a disturbed environmental light/dark (LD) cycle affects the fetal SCN. We exposed pregnant Wistar rats to two different challenges - a 6-h phase shift in the LD cycle on gestational day 14, or exposure to constant light (LL) throughout pregnancy - and detected the impact on gene expression profiles in 19-day-old fetuses.

Modulation of single cell circadian response to NMDA by diacylglycerol lipase inhibition reveals a role of endocannabinoids in light entrainment of the suprachiasmatic nucleus.

Suprachiasmatic nucleus (SCN) of the hypothalamus is the master clock that drives circadian rhythms in physiology and behavior and adjusts their timing to external cues. Neurotransmitter glutamate and glutamatergic receptors sensitive to N-methyl-d-aspartate (NMDA) play a dual role in the SCN by coupling astrocytic and neuronal single cell oscillators and by resetting their phase in response to light. Recent reports suggested that signaling by endogenous cannabinoids (ECs) participates in both of these functions.

Subjective status and perceived legitimacy across countries.

The relationships between subjective status and perceived legitimacy are important for understanding the extent to which people with low status are complicit in their oppression. We use novel data from 66 samples and 30 countries ( = 12,788) and find that people with higher status see the social system as more legitimate than those with lower status, but there is variation across people and countries. The association between subjective status and perceived legitimacy was never negative at any levels of eight moderator variables, although the positive association was sometimes reduced.

Urothelial Carcinoma of the Bladder Induces Endothelial Cell Activation and Hypercoagulation.

Cancer-related venous thromboembolisms (VTE) are associated with metastasis and reduced survival in patients with urothelial cancer of the bladder. Although previous reports suggest the contribution of tissue factor and podoplanin, the mechanistic linkage between VTE and bladder cancer cell-derived molecules is unknown. Therefore, we compared distinct procoagulant pathways in four different cell lines.

Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently.

The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function.

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion.

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype.

Smart antimicrobial efficacy employing pH-sensitive ZnO-doped diamond-like carbon coatings.

One of the main challenges in endoprosthesis surgeries are implant-associated infections and aseptic-loosenings, caused by wear debris. To combat these problems, the requirements to surfaces of endoprostheses are wear-resistance, low cytotoxicity and antimicrobial efficacy. We here present antimicrobial coatings with a smart, adaptive release of metal ions in case of infection, based on ZnO-nanoparticles embedded in diamond-like carbon (DLC).

Circadian profiling reveals distinct regulation of endocannabinoid system in the rat plasma, liver and adrenal glands by light-dark and feeding cycles.

Circadian clocks coordinate physiological and behavioral rhythms that allow the organism to anticipate and adapt to daily changes in environment. The clock-driven cellular oscillations are highly tissue specific to efficiently fine-tune local signaling, manage energy use and segregate incompatible processes. In most peripheral tissues, food acts as the main cue that entrains the oscillations to external time.

Fraud and Understanding the Moral Mind: Need for Implementation of Organizational Characteristics into Behavioral Ethics.

The development of behavioral ethics has brought forth a detailed understanding of the processes of moral perception, decision-making and behavior within and beyond organizations and communities. However, prescriptive recommendations of behavioral research regarding how to support an ethical environment often underestimate the specifics of organizational characteristics that may encourage the occurrence and persistence of dishonesty, especially regarding deception as a desired action in some instances by some employees and managers. Furthermore, behavioral research does not adequately recognize the notion that dishonesty can be sometimes viewed as an acceptable cost for some expected traits or skills of an employee such as intelligence or creativity.

Biological, environmental and socioeconomic determinants of the human birth sex ratio in the Czech Republic.

The Trivers-Willard Hypothesis (TWH) states that parents in good conditions bias the sex ratio towards sons and parents in poor conditions bias the sex ratio towards daughters. This study used data from a large nationwide population dataset (N=1,401,851) from the Czech Republic - a modern contemporary society. The study included air pollution and property prices in the TWH estimation, and had a more detailed focus on stillbirths than previous studies.

Development and Entrainment of the Fetal Clock in the Suprachiasmatic Nuclei: The Role of Glucocorticoids.

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels.

Implicit time-place conditioning alters Per2 mRNA expression selectively in striatum without shifting its circadian clocks.

Animals create implicit memories of the time of day that significant events occur then anticipate the recurrence of those conditions at the same time on subsequent days. We tested the hypothesis that implicit time memory for daily encounters relies on the setting of the canonical circadian clockwork in brain areas involved in the formation or expression of context memories. We conditioned mice to avoid locations paired with a mild foot shock at one of two Zeitgeber times set 8 hours apart.

The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian Activity.

The McGill-R-Thy1-APP transgenic rat is an animal model of the familial form of Alzheimer's disease (AD). This model mirrors several neuropathological hallmarks of the disease, including the accumulation of beta-amyloid and the formation of amyloid plaques (in homozygous animals only), neuroinflammation and the gradual deterioration of cognitive functions even prior to plaque formation, although it lacks the tauopathy observed in human victims of AD. The goal of the present study was a thorough characterization of the homozygous model with emphasis on its face validity in several domains of behavior known to be affected in AD patients, including cognitive functions, motor coordination, emotionality, sociability, and circadian activity patterns.

Tight Junction barriers in human hair follicles - role of claudin-1.

Barrier function of hair follicles (HFs) is of great interest because they might be an entry port for allergens/pathogens, but could on the other hand be used for drug delivery or vaccination. Therefore we investigated tight junction (TJ) barrier function in human HFs. We show that there is a TJ barrier in the outermost living layer bordering to the environment from the infundibulum to the lower central part and between Henle's and Huxles layer of anagen HFs.

Economic Holobiont: Influence of Parasites, Microbiota and Chemosignals on Economic Behavior.

The article is a perspective on utilization of microorganisms and chemosignals in studying human economic behavior. Research in biological roots of economic development has already confirmed that parasitic pressure influenced the creation and development of cultural norms and institutions. However, other effects of microorganisms on human groups and individual decision-making and behavior are heavily understudied.