Early detection of insomnia symptoms would be a potential intervention point to improve both sleep quality and prevent cognitive decline in later life. However, intervention studies are needed.Vertebrates show substantial interspecific variation in brain size in relation to body mass. It has long been recognized that the evolution of large brains is associated with both costs and benefits, and it is their net benefit which should be favoured by natural selection. On one hand, the substantial energetic cost imposed by the maintenance of neural tissue is expected to compromise the energetic budget of organisms with large brains and their investment in other critical organs (expensive brain framework, EBF) or important physiological process, such as somatic maintenance and repair, thus accelerating ageing that shortens lifespan, as predicted by the disposable soma theory (DST). However, selection towards larger brain size can provide cognitive benefits (e.g., high behavioural flexibility) that may mitigate extrinsic mortality pressures, and thus may indirectly select for slower ageing that prolongs lifespan, as predicted by the cognitive buffer hypothesis (CBH). The relationship between longevity and brain size has been investigated to date only among terrestrial vertebrates, although the same selective forces acting on those species may also affect vertebrates living in aquatic habitats, such as fish. Thus, whether this evolutionary trade-off for brain size and longevity exists on a large scale among fish clades remains to be addressed. In this study, using a global dataset of 407 fish species, I undertook the first phylogenetic test of the brain size/longevity relationship in aquatic vertebrate species. The study revealed a negative relationship between brain size and longevity among cartilaginous fish confirming EBF and DST. However, no pattern emerged among bony fish species. Among sharks and rays, the high metabolic cost of producing neural tissue transcends the cognitive benefits of evolving a larger brain. Consequently, my findings suggest that the cost of maintaining brain tissue is relatively higher in ectothermic species than in endothermic ones.In the course of studies on the enhancement of 1,2-dibromoethane-induced DNA base pair mutations by O6-alkylguanine-DNA alkyltransferase (AGT, MGMT), we discovered the facile reaction of AGT with an abasic site in DNA, leading to covalent cross-linking. The binding of AGT differs from the mechanism reported for the protein HMCES; instead it appears to involve formation of a stable thioglycoside. Facile cross-linking was also observed with the protease papain, which like AGT has a low pKa cysteine, and the tripeptide glutathione.Each heartbeat begins with the generation of an action potential in pacemaking cells in the sinoatrial node. This signal triggers contraction of cardiac muscle through a process termed excitation-contraction (EC) coupling. EC coupling is initiated in dyadic structures of cardiac myocytes, where ryanodine receptors in the junctional sarcoplasmic reticulum come into close apposition with clusters of CaV1.2 channels in invaginations of the sarcolemma. Cooperative activation of CaV1.2 channels within these clusters causes a local increase in intracellular Ca2+ that activates the juxtaposed ryanodine receptors. A salient feature of healthy cardiac function is the reliable and precise beat-to-beat pacemaking and amplitude of Ca2+ transients during EC coupling. In this review, we discuss recent discoveries suggesting that the exquisite reproducibility of this system emerges, paradoxically, from high variability at subcellular, cellular, and network levels. This variability is attributable to stochastic fluctuations g stochasticity, which counterintuitively manifests as reliable, consistent Ca2+ transients during EC coupling, also allows for rapid changes in cardiac rhythmicity and contractility in health and disease.

Due to the exponential growth in the Latinx older adult population, culturally responsive services are needed, especially since most healthcare providers are non-Latinx with limited Spanish or bilingual skills. One place to start is by drawing a formative assessment of the healthcare providers’ knowledge and awareness of the healthcare needs of Latinx older adults.

Focus groups were conducted to explore the healthcare providers’ knowledge and awareness of cultural and structural barriers and facilitators to accessing health care services for Latinx older adults.

Results note that healthcare providers perceived the healthcare needs for Latinx older adults to be underutilized for healthcare services, preventive interventions for healthy diet/lifestyle, and healthcare knowledge. Providers reported Latinx family over-involvement, religiosity, immigration, and language/lack of interpreters as barriers to seeking timely healthcare. Finally, healthcare providers said that family support, the location of healthcare services, and community-based partnerships were all facilitators for seeking healthcare.

Findings suggest providers’ conflicting perspectives toward the Latinx communities.

Healthcare services can consider implementing trainings for non-Latinx providers to recognize conflicting perspectives and reduce implicit bias toward the Latinx communities.

Healthcare services can consider implementing trainings for non-Latinx providers to recognize conflicting perspectives and reduce implicit bias toward the Latinx communities.Recently, identifying promising new two-dimensional (2D) materials with low-symmetry structures has aroused great interest for developing monolithic polarization-sensitive photodetectors with small volume. Here, after comprehensive research of the in-plane anisotropic structure and electronic and optoelectronic properties of layered γ-InSe, a superior responsivity polarization-sensitive photodetector based on multilayer γ-InSe is constructed by a facile method. Notably, the conductance and carrier mobility of the device along the armchair direction are 11.8 and 2.35 times larger than those along the zigzag direction, respectively. Benefitting from the high efficiency of light absorption and excellent carrier mobility (221 cm2 V-1 s-1) of our multilayered γ-InSe along the armchair direction, the device exhibits a superior responsivity of 127 A/W and an external quantum efficiency (EQE) of 104%. Especially, the highest responsivity along the armchair direction of our γ-InSe polarization-sensitive photodetectors can reach as high as 78.5 A/W under polarized light. This value is much higher than those of other devices even under unpolarized light. This work not only provides an insight into the in-plane anisotropic properties of 2D layered γ-InSe but also proposes a stable and environmentally friendly candidate for anisotropic optoelectronic applications.At mitotic entry, reorganization of the actomyosin cortex prompts cells to round-up. Proteins of the ezrin, radixin, and moesin family (ERM) play essential roles in this process by linking actomyosin forces to the plasma membrane. Yet, the cell-cycle signal that activates ERMs at mitotic entry is unknown. By screening a compound library using newly developed biosensors, we discovered that drugs that disassemble microtubules promote ERM activation. We further demonstrated that disassembly of interphase microtubules at mitotic entry directs ERM activation and metaphase cell rounding through GEF-H1, a Rho-GEF inhibited by microtubule binding, RhoA, and its kinase effector SLK. We finally demonstrated that GEF-H1 and Ect2, another Rho-GEF previously identified to control actomyosin forces, act together to drive activation of ERMs and cell rounding in metaphase. In summary, we report microtubule disassembly as a cell-cycle signal that controls a signaling network ensuring that actomyosin forces are efficiently integrated at the plasma membrane to promote cell rounding at mitotic entry.Tissue-resident macrophages play essential functions in the maintenance of tissue homeostasis and repair. Recently, the endocardium has been reported as a de novo hemogenic site for the contribution of hematopoietic cells, including cardiac macrophages, during embryogenesis. These observations challenge the current consensus that hematopoiesis originates from the hemogenic endothelium within the yolk sac and dorsal aorta. Whether the developing endocardium has such a hemogenic potential requires further investigation. Here, we generated new genetic tools to trace endocardial cells and reassessed their potential contribution to hematopoietic cells in the developing heart. Fate-mapping analyses revealed that the endocardium contributed minimally to cardiac macrophages and circulating blood cells. Instead, cardiac macrophages were mainly derived from the endothelium during primitive/transient definitive (yolk sac) and definitive (dorsal aorta) hematopoiesis. Our findings refute the concept of endocardial hematopoiesis, suggesting that the developing endocardium gives rise minimally to hematopoietic cells, including cardiac macrophages.

Biallelic POLR3B mutations cause a rare hypomyelinating leukodystrophy. De novo POLR3B heterozygous mutations were recently associated with afferent ataxia, spasticity, variable intellectual disability, and epilepsy, and predominantly demyelinating sensorimotor peripheral neuropathy.

We performed whole-exome sequencing (WES) of DNA samples from 804 Charcot-Marie-Tooth (CMT) cases that could not be genetically diagnosed by DNA-targeted resequencing microarray using next-generation sequencers. Using WES data, we analyzed the POLR3B mutations and confirmed their clinical features.

We identified de novo POLR3B heterozygous missense mutations in two patients. These patients presented with early-onset demyelinating sensorimotor neuropathy without ataxia, spasticity, or cognitive impairment. Patient 1 showed mild cerebellar atrophy and spinal cord atrophy on magnetic resonance imaging and eventually died of respiratory failure in her 50s. We classified these mutations as pathogenic based on segregation studies, comparison with control database, and in silico analysis.

Our study is the third report on patients with demyelinating CMT harboring heterozygous POLR3B mutations and verifies the pathogenicity of POLR3B mutations in CMT. Although extremely rare in our large Japanese case series, POLR3B mutations should be added to the CMT-related gene panel for comprehensive genetic screening, particularly for patients with early-onset demyelinating CMT.

Our study is the third report on patients with demyelinating CMT harboring heterozygous POLR3B mutations and verifies the pathogenicity of POLR3B mutations in CMT. Although extremely rare in our large Japanese case series, POLR3B mutations should be added to the CMT-related gene panel for comprehensive genetic screening, particularly for patients with early-onset demyelinating CMT.We report a transparent and flexible polyimide (PI)-doped single-layer (PSL) phototransistor for the detection of visible light. The PSL was deposited on a SiO2 gate insulator by a co-sputtering process using amorphous indium-gallium-zinc oxide (IGZO) and PI targets simultaneously. The PSL acted as both a channel layer and a visible-light absorption layer. PI is one of the few flexible organic materials that can be fabricated into sputtering targets. Compared with the IGZO phototransistor without PI doping, the PSL phototransistor exhibited improved optoelectronic characteristics under illumination with 635 nm red light of 1 mW/mm2 intensity; the obtained photoresponsivity ranged from 15.00 to 575.00 A/W, the photosensitivity from 1.38 × 101 to 9.86 × 106, and the specific detectivity from 1.35 × 107 to 5.83 × 1011 Jones. These improvements are attributed to subgap states induced by the PI doping, which formed decomposed organic molecules, oxygen vacancies, and metal hydroxides. Furthermore, a flexible PSL phototransistor was fabricated and showed stable optoelectronic characteristics even after 10,000 bending tests.