St. Louis University High School

INTRODUCTIONCircadian rhythm disruption is an early symptom of Alzheimer's disease (AD), though it remains unclear how the light‐dark (LD) cycle and the central circadian clock in the suprachiasmatic nucleus (SCN) influence AD pathobiology.METHODSWe disrupted the SCN clock via deletion of Bmal1 in GABAergic neurons (VGAT‐iCre; Bmal1 KO), crossed to the 5xFAD amyloid‐beta (Aβ) model, and raised mice under LD or constant dark (DD) conditions. We examined circadian rhythms, sleep, Aβ plaques, and phospho‐tau (p‐tau) pathology, and gene expression.RESULTSVGAT‐Bmal1 knockout (KO) mice showed weakened rhythms in LD and arrhythmicity in DD conditions. LD conditions promoted Aβ plaque accumulation in 5xFAD mice, while VGAT‐Bmal1 deletion reduced amyloid precursor protein (APP) cleavage, Aβ plaque accumulation, and peri‐plaque p‐tau, and induced extracellular matrix (ECM) gene expression in LD, but not DD, conditions.DISCUSSIONIn 5xFAD mice, LD cycles interact with the central circadian clock to reinforce Aβ deposition, while central clock disruption or constant darkness unexpectedly mitigate plaque pathology.Highlights5xFAD mice accumulate more Aβ plaque pathology when raised under standard LD conditions than when raised in DD conditions.VGAT‐Bmal1 KO eliminates locomotor rhythms in DD conditions and weakens locomotor, sleep, and transcriptional rhythms in LD conditions.VGAT‐Bmal1 KO; 5xFAD mice aged in LD conditions accumulated less total Aβ plaque and peri‐plaque p‐tau than their Cre− littermates. VGAT‐Bmal1 KO had no effect onplaque pathology in mice aged in constant darkness.Amyloid precursor protein carboxy terminal fragments (APP‐CTFs) were suppressed in VGAT‐Bmal1 KO mice under LD conditions, suggesting reduced Aβ production.Transcriptomic analysis shows induction of AEBP1 in VGAT‐Bmal1 KO, which regulates ECM genes and has been associated with AD pathology in humans.

Sleep disturbances and cognitive decline are intricately connected, and both are prevalent in aging populations and individuals with neurodegenerative disorders such as Alzheimer's disease (AD) and other dementias. Sleep is vital for cognitive functions including memory consolidation, executive function, and attention. Disruption in these processes is associated with cognitive decline, although causal evidence is mixed. This review delves into the bidirectional relationship between alterations in sleep and cognitive impairment, exploring key mechanisms such as amyloid-β accumulation, tau pathology, synaptic homeostasis, neurotransmitter dysregulation, oxidative stress, and vascular contributions. Evidence from both experimental research and population-based studies underscores the necessity of early interventions targeting sleep to mitigate risks of neurodegenerative diseases. A deeper understanding of the interplay between sleep and cognitive health may pave the way for innovative strategies to prevent or reduce cognitive decline through improved sleep management.

Abstract When a hard‐working, justice‐oriented group of pre‐service English teachers (PSTs) identified themselves as non‐readers, two professors and a program alumna at a flagship university in the Midwest were inspired to create a young adult (YA) literature book club. Through monthly meetings, PSTs (and later first‐year teachers) gathered in a welcoming third space (Gutiérrez, 2008) to discuss YA books as readers and as teachers, considering both the experience of reading and the purpose for using these texts in their classrooms (Rosenblatt, 1994). Outcomes from Overbooked: An Educators' Book Club suggest that pre‐service teachers can find reading joy when offered a supportive space and community to grow as readers and teachers.

Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother-infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter-daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter-daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. RESEARCH HIGHLIGHTS: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake. Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates. Maternal inter-daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area.

Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

We investigated adolescents' feelings of thermal comfort during the educational process in various geographical locations far apart and present recommendations for the adjustment of the thermal environment in schools. The prospective international multicenter study took place in 8 locations on different continents. The survey in the form of a questionnaire was carried out among 2800 healthy high school students. The study was divided into "cold season survey," "warm-season survey," and heat wave survey. The statistically significant difference between the "cold season survey" score of 4.04 (discomfort) and "warm-season survey" score of 3.47 (slight discomfort) (p=.04) indicates that students feel more thermal discomfort during winter months in all 8 locations. The heat wave survey score was 4.53 (discomfort). During the cold season, 29.24% of high school students felt themselves in full thermal comfort and 76.48% of the students felt themselves relatively comfortable (slightly cool-comfortable-slightly warm). Even during the ongoing process of climate change, the cold season discomfort remains the main problem for students in classes. This tendency is present in different continents as a universal problem. We recommend keeping an entrance hall and classroom temperatures at different levels and to advise students about proper clothing.

Recombination mediator proteins (RMPs) are important for genome stability in all organisms and support two reactions: the recombinase binding to single‐stranded (ss)DNA to initiate homologous recombination (HR) and strand annealing. Both reactions are inhibited by ssDNA binding proteins (e.g. gp32, SSB, RPA). RMPs promote DNA transfer from SSB to recombinase or to anneal DNA. In spite of two ubiquitous functions, RMPs lack sequence and structural homology. Previously, we demonstrated that E. coli RMPs, RecOR, do not dismiss SSB from ssDNA, but form the complex with SSB altering the conformation of bound ssDNA. RecO binds SSB and the complex promotes DNA annealing or RecA loading in the absence or presence of RecR, respectively. Surprisingly, mycobacterial RecO does not interact with SSB. Yet, both proteins form complex on the shared ssDNA substrate in both pathways.In mycobacteria, RecFOR deletion reduces clastogens resistance to the same degree as a deletion of the major homologous recombinase RecA. Chromosomal DNA break repair assay surprisingly revealed that all three proteins are involved in both pathways: HR and annealing. Here we will describe biochemical studies of DNA annealing and strand exchange reactions supported by mycobacterial RecFOR. The selection of one or the other pathway is dictated by the availability of recombinase or complimentary strand and the stoichiometry of the DNA‐protein complexes. We believe that the intermediate complex of RMP with SSB and ssDNA represents a common critical step in reactions supported by all RMPs during HR and strand annealing DNA repair pathways in all organisms.