A glial circadian gene expression atlas reveals cell type and disease-specific reprogramming in response to amyloid pathology or aging.

While circadian rhythm disruption may promote neurodegenerative disease, how aging and neurodegenerative pathology impact circadian gene expression patterns in different brain cell types is unknown. Here, we used translating ribosome affinity purification methods to define the circadian translatomes of astrocytes, microglia, and bulk cerebral cortex, in healthy mouse brain and in the settings of amyloid-beta plaque pathology or aging. Our data reveal that glial circadian translatomes are highly cell type-specific and exhibit profound, context-dependent reprogramming of rhythmic transcripts in response to amyloid pathology or aging.

Microglia phagocytic mechanisms: Development informing disease.

Microglia are tissue-resident macrophages and professional phagocytes of the central nervous system (CNS). In development, microglia-mediated phagocytosis is important for sculpting the cellular architecture. This includes the engulfment of dead/dying cells, pruning extranumerary synapses and axons, and phagocytosing fragments of myelin sheaths.

Kir6.2-K channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis.

Unlabelled: Metabolism plays an important role in the maintenance of vigilance states (e.g. wake, NREM, and REM).

Neuronal deletion of the circadian clock gene Bmal1 induces cell-autonomous dopaminergic neurodegeneration.

Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP.

Maternal Caffeine Consumption and Its Impact on the Fetus: A Review.

Maintaining a healthy diet is essential for pregnant women and their developing fetuses, including being mindful of caffeine consumption. While consuming caffeine during pregnancy is generally safe, there is a concern among healthcare practitioners about whether it can adversely impact pregnancy. There is a lack of accurate information about the effects of caffeine on fetal development and inadequate education on the risks of excessive caffeine intake during pregnancy.

Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice.

Alzheimer's disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation.

Correspondence measures for assessing replication success.

Given recent evidence challenging the replicability of results in the social and behavioral sciences, critical questions have been raised about appropriate measures for determining replication success in comparing effect estimates across studies. At issue is the fact that conclusions about replication success often depend on the measure used for evaluating correspondence in results. Despite the importance of choosing an appropriate measure, there is still no widespread agreement about which measures should be used.

An astrocyte BMAL1-BAG3 axis protects against alpha-synuclein and tau pathology.

The circadian clock protein BMAL1 modulates glial activation and amyloid-beta deposition in mice. However, the effects of BMAL1 on other aspects of neurodegenerative pathology are unknown. Here, we show that global post-natal deletion of Bmal1 in mouse tauopathy or alpha-synucleinopathy models unexpectedly suppresses both tau and alpha-synuclein (αSyn) aggregation and related pathology.

The construct of cuteness: A validity study for measuring content and evoked emotions on social media.

Social media users are often exposed to cute content that evokes emotional reactions and influences them to feel or behave certain ways. The cuteness phenomenon in social media has been scarcely studied despite its prevalence and potential to spread quickly and affect large audiences. The main framework for understanding cuteness and emotions related to cuteness outside of social media is baby schema (having juvenile characteristics), which triggers parental instincts.

Deuterium-enriched water ties planet-forming disks to comets and protostars.

Water is a fundamental molecule in the star and planet formation process, essential for catalysing the growth of solid material and the formation of planetesimals within disks. However, the water snowline and the HDO:HO ratio within proto-planetary disks have not been well characterized because water only sublimates at roughly 160 K (ref. ), meaning that most water is frozen out onto dust grains and that the water snowline radii are less than 10 AU (astronomical units).

Factors Predicting the Extent to which STEM Students Value Cross-Disciplinary Skills: A Study across Four Institutions.

Expectancy-value theory of motivation (EVT) suggests that student values influence their likelihood of putting in the effort required to learn, and these values can be shaped by student characteristics, such as their experiences, sociodemographics, and disciplinary norms. To understand the extent to which these characteristics relate to students' values, we surveyed 1162 graduating science, technology, engineering, and mathematics (STEM) students across four universities using the previously developed and validated Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U). The STEP-U survey included Likert questions to capture students' values of 27 cross-disciplinary skills and the frequency with which they experienced 27 instructional methods thought to develop particular skills.

Monitored and Modeled Ambient Air Concentrations of Ethylene Oxide: Contextualizing Health Risk for Potentially Exposed Populations in Georgia.

Unlabelled: Recent studies have monitored and modeled long-term ambient air concentrations of ethylene oxide (EO) around emitting facilities in Georgia with the intent of informing risk management of potentially exposed nearby residential populations. Providing health context for these data is challenging because the U.S.

Functional Characterization of the Variant p.E60Q in Non-Syndromic Hearing Loss Patients.

Hereditary hearing loss (HHL) is a common genetic disorder accounting for at least 60% of pre-lingual deafness in children, of which 70% is inherited in an autosomal recessive pattern. The long tradition of consanguinity among the Qatari population has increased the prevalence of HHL, which negatively impacts the quality of life. Here, we functionally validated the pathogenicity of the c.

Bacterial sepsis increases hippocampal fibrillar amyloid plaque load and neuroinflammation in a mouse model of Alzheimer's disease.

Background: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss.

Ethylene Oxide Exposure in U.S. Populations Residing Near Sterilization and Other Industrial Facilities: Context Based on Endogenous and Total Equivalent Concentration Exposures.

Given ubiquitous human exposure to ethylene oxide (EO), regardless of occupation or geography, the current risk-specific concentrations (RSCs: 0.0001-0.01 ppb) from the U.

REV-ERBα mediates complement expression and diurnal regulation of microglial synaptic phagocytosis.

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including and , in the hippocampus. BMAL1 regulates expression of the transcriptional repressor REV-ERBα, and deletion of REV-ERBα causes increased expression of transcript in neurons and astrocytes as well as C3 protein primarily in astrocytes.

Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice.

Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM.

Evaluating Circadian Dysfunction in Mouse Models of Alzheimer's Disease: Where Do We Stand?

Circadian dysfunction has been described in patients with symptomatic Alzheimer's disease (AD), as well as in presymptomatic phases of the disease. Modeling this circadian dysfunction in mouse models would provide an optimal platform for understanding mechanisms and developing therapies. While numerous studies have examined behavioral circadian function, and in some cases clock gene oscillation, in mouse models of AD, the results are variable and inconsistent across models, ages, and conditions.

A single-nucleotide polymorphism in a ApiAP2 transcription factor alters the development of host immunity.

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite () NK65 allowed infected mice to mount a T helper cell 1 (T1)-type immune response that controlled subsequent infections.

Development of a novel method for estimating dermal contact with hand-applied cleaning solutions.

Quantitatively characterizing dermal exposure for workers and consumers performing tasks with hand-applied cleaning solution is complex as many of the assessment variables are scenario specific. One of the key variables necessary for quantitatively estimating dermal exposure is the surface area of the hand contacted by the cleaning solution. However, no relevant data or methods are available in the literature.

Inhibition of REV-ERBs stimulates microglial amyloid-beta clearance and reduces amyloid plaque deposition in the 5XFAD mouse model of Alzheimer's disease.

A promising new therapeutic target for the treatment of Alzheimer's disease (AD) is the circadian system. Although patients with AD are known to have abnormal circadian rhythms and suffer sleep disturbances, the role of the molecular clock in regulating amyloid-beta (Aβ) pathology is still poorly understood. Here, we explored how the circadian repressors REV-ERBα and β affected Aβ clearance in mouse microglia.

Reevaluation of Historical Exposures to Ethylene Oxide Among U.S. Sterilization Workers in the National Institute of Occupational Safety and Health (NIOSH) Study Cohort.

The 2016 U.S. Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) assessment for ethylene oxide (EO) estimated a 10 increased inhalation cancer risk of 0.