Induction of somatic cell haploidy by premature cell division.

Canonical mitotic and meiotic cell divisions commence with replicated chromosomes consisting of two sister chromatids. Here, we developed and explored a model of premature cell division, where nonreplicated, G0/G1-stage somatic cell nuclei are transplanted to the metaphase cytoplasm of mouse oocytes. Subsequent cell division generates daughter cells with reduced ploidy. Unexpectedly, genome sequencing analysis revealed proper segregation of homologous chromosomes, resulting in complete haploid genomes. We observed a high occurrence of somatic genome haploidization in nuclei from inbred genetic backgrounds but not in hybrids, emphasizing the importance of sequence homology between homologs. These findings suggest that premature cell division relies on mechanisms similar to meiosis I, where genome haploidization is facilitated by homologous chromosome interactions, recognition, and pairing. Unlike meiosis, no evidence of recombination between somatic cell homologs was detected. Our study offers an alternative in vitro gametogenesis approach by directly reprogramming diploid somatic cells into haploid oocytes.

Distinct longevity mechanisms across and within species and their association with aging.

Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration. Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan. Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions.

Self-aligned single-electrode actuation of tangential and wineglass modes using PMN-PT.

Considering the evolution of rotation sensing and timing applications realized in micro-electro-mechanical systems (MEMS), flexural mode resonant shapes are outperformed by bulk acoustic wave (BAW) counterparts by achieving higher frequencies with both electrostatic and piezoelectric transduction. Within the 1-30 MHz range, which hosts BAW gyroscopes and timing references, piezoelectric and electrostatic MEMS have similar transduction efficiency. Although, when designed intelligently, electrostatic transduction allows self-alignment between electrodes and the resonator for various BAW modes, misalignment is inevitable regarding piezoelectric transduction of BAW modes that require electrode patterning. In this paper transverse piezoelectric actuation of [011] oriented single crystal lead magnesium niobate-lead titanate (PMN-PT) thin film disks are shown to excite the tangential mode and family of elliptical compound resonant modes, utilizing a self-aligned and unpatterned electrode that spans the entire disk surface. The resonant mode coupling is achieved by employing a unique property of [011] PMN-PT, where the in-plane piezoelectric coefficients have opposite signs. Fabricating 1-port disk transducers, RF reflection measurements are performed that demonstrate the compound mode family shapes in the 1-30 MHz range. Independent verification of mode transduction is achieved using in-plane displacement measurements with Polytec's laser Doppler vibrometer (LDV). While the tangential mode achieves a 40o/s dithering rate at 335 kHz resonant frequency, the n = 2 wine-glass mode achieves 11.46 nm tip displacement at 8.42 MHz resonant frequency on a radius of 60 µm disk resonator in air. A single electrode resonator that can excite both tangential and wine-glass modes with such metrics lays the foundation for a BAW MEMS gyroscope with a built-in primary calibration stage.

Theoretical and Experimental Studies on Sensitivity and Bandwidth of Thickness-Mode Driving Hydrophone Utilizing A 2-2 Piezoelectric Single Crystal Composite.

Piezoelectric composites, which consist of a piezoelectric material and a polymer, have been extensively studied for the applications of underwater sonar sensors and medical diagnostic ultrasonic transducers. Acoustic sensors utilizing piezoelectric composites can have a high sensitivity and wide bandwidth because of their high piezoelectric coefficient and low acoustic impedance compared to single-phase piezoelectric materials. In this study, a thickness-mode driving hydrophone utilizing a 2-2 piezoelectric single crystal composite was examined. From the theoretical and numerical analysis, material properties that determine the bandwidth and sensitivity of the thickness-mode piezoelectric plate were derived, and the voltage sensitivity of piezoelectric plates with various configurations was compared. It was shown that the 2-2 composite with [011] poled single crystals and epoxy polymers can provide high sensitivity and wide bandwidth when used for hydrophones with a thickness resonance mode. The hydrophone element was designed and fabricated to have a thickness mode at a frequency around 220 kHz by attaching a composite plate of quarter-wavelength thickness to a hard baffle. The fabricated hydrophone demonstrated an open circuit voltage sensitivity of more than -180 dB re 1 V/µPa at the resonance frequency and a -3 dB bandwidth of more than 55 kHz. The theoretical and experimental studies show that the 2-2 single crystal composite can have a high sensitivity and wide bandwidth compared to other configurations of piezoelectric elements when they are used for thickness-mode hydrophones.

The teaching of geriatric dentistry in South Korean dental schools.

OBJECTIVE: The purpose of this study was to investigate the curriculum of geriatric dentistry for undergraduates in Korean dental schools. BACKGROUND: For development purposes, it was necessary to compare geriatric dentistry education programmes in South Korea to programmes in the United States and Europe. METHODS: The most recent curriculum and related information on geriatric dentistry at the undergraduate level in all 11 dental schools in South Korea were collected by both official letter and e-mail. A symposium for gathering expert opinions to improve geriatric dentistry education in South Korea was also held. The collected data were analysed, and the expert opinions at the symposium were summarised. RESULTS: Six of 11 schools had a didactic course as compulsory and three schools as elective. The course was usually conducted as a form of integrated lectures, and the level of standardisation of lecture content was very low. There were no topics for older people who cannot access dental clinics due to functional frailty or disability. No dental school-affiliated hospitals had an independent department for geriatric dentistry. No schools provided clinical teaching for geriatric dentistry. There were no outreach programmes for geriatric dentistry. CONCLUSIONS: The educational curriculum for geriatric dentistry in South Korea was insufficient to cope with social and demographic changes. Curriculum content should include clinical practice education and needs to be focused on frail and dependent older adult patients. An essential educational curriculum and core competency for geriatric dentistry should be prepared.

Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis.

Thioredoxin/glutathione reductase (TXNRD3) is a selenoprotein composed of thioredoxin reductase and glutaredoxin domains. This NADPH-dependent thiol oxidoreductase evolved through gene duplication within the Txnrd family, is expressed in the testes, and can reduce both thioredoxin and glutathione in vitro; however, the function of this enzyme remains unknown. To characterize the function of TXNRD3 in vivo, we generated a strain of mice bearing deletion of Txnrd3 gene. We show that these Txnrd3 knockout mice are viable and without discernable gross phenotypes, and also that TXNRD3 deficiency leads to fertility impairment in male mice. We found that Txnrd3 knockout animals exhibited a lower fertilization rate in vitro, a sperm movement phenotype, and an altered thiol redox status in sperm cells. Proteomic analyses further revealed a broad range of substrates reduced by TXNRD3 during sperm maturation, presumably as a part of sperm quality control. Taken together, these results show that TXNRD3 plays a critical role in male reproduction via the thiol redox control of spermatogenesis.

Flexible, Elastic, and Superhydrophobic/Superoleophilic Adhesive for Reusable and Durable Water/Oil Separation Coating.

This study investigates a highly flexible/stretchable and mechanically durable superhydrophobic/superoleophilic coating for efficient oil/water separation and oil absorption. The coating is applied via a simple immersion process using a mixed solution of a biocompatible adhesive (ethyl cyanoacrylate, ECA), a highly stretchable polymer (polycaprolactone, PCL), and superhydrophobic/superoleophilic nanoparticles (fluorine-coated silica nanoparticles, F-SiO2 NPs) in a solvent, followed by solvent evaporation and ECA polymerization. Polymerized ECA (poly-ECA) in the coating material strongly adheres the F-SiO2 NPs to the substrate surface, while PCL bestows the rigid poly-ECA with high flexibility. A coated polyurethane sponge exhibits superhydrophobicity (water contact angle of >150°), while retaining robust mechanical stability and flexibility/elasticity. This provides an efficient means of cleaning oil spills with high selectivity, even after mechanical abrasion (>99% separation efficiency is retained after 120 tape test cycles and 50 rubbing test cycles), with excellent reusability.

Epigenetic aging of the demographically non-aging naked mole-rat.

The naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age. We develop an epigenetic aging clock that accurately predicts the NMR age. We show that these animals age much slower than mice and much faster than humans, consistent with their known maximum lifespans. Interestingly, patterns of age-related changes of clock sites in Tert and Prpf19 differ between NMRs and mice, but there are also sites conserved between the two species. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.

Maintenance of genome sequence integrity in long- and short-lived rodent species.

DNA mutations in somatic cells have been implicated in the causation of aging, with longer-lived species having a higher capacity to maintain genome sequence integrity than shorter-lived species. In an attempt to directly test this hypothesis, we used single-cell whole-genome sequencing to analyze spontaneous and bleomycin-induced somatic mutations in lung fibroblasts of four rodent species with distinct maximum life spans, including mouse, guinea pig, blind mole-rat, and naked mole-rat, as well as humans. As predicted, the mutagen-induced mutation frequencies inversely correlated with species-specific maximum life span, with the greatest difference observed between the mouse and all other species. These results suggest that long-lived species are capable of processing DNA damage in a more accurate way than short-lived species.

Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging.

The notion that the germ line does not age goes back to the 19th-century ideas of August Weismann. However, being metabolically active, the germ line accumulates damage and other changes over time, i.e., it ages. For new life to begin in the same young state, the germ line must be rejuvenated in the offspring. Here, we developed a multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e., rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (ground zero) marks the beginning of organismal aging.

A strategy for preparing controllable, superhydrophobic, strongly sticky surfaces using SiO2@PVDF raspberry core-shell particles.

In nature, wetting by water droplets on superhydrophobic materials is governed by the Cassie-Baxter or Wenzel models. Moreover, sticky properties, derived from these types of wettings, are required for a wide range of applications involving superhydrophobic materials. As a facile new strategy, a method employing a gaseous fluorine precursor to fabricate core-shell particles, comprising perfectly shaped fluorine shells with adjustable adhesive strength, is described in this paper. Silica was used as the hydrophilic core, while polyvinylidene fluoride (PVDF) was used for the hydrophobic shell coating, forming a raspberry-like shape. In addition, controlling the amount of PVDF coated on the silica surface enabled the water droplets to come into contact with both the PVDF of the shell and the silica of the core, thereby controlling both the superhydrophobicity and the adhesive strength. Thus, the synthesized particles formed a structured coating with controllable stickiness and contact angles of 131-165°. Furthermore, on surfaces with high adhesivity, the water droplets remained stable at tilt angles of 90° and 180° even under a strong centrifugal force, whereas on surfaces with low adhesivity, the water droplets slid off when the substrate was tilted at 4°.

Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human.

Caffeine occurs naturally in various foods, such as coffee, tea, and cocoa, and it has been used safely as a mild stimulant for a long time. However, excessive caffeine consumption (1~1.5 g/day) can cause caffeine poisoning (caffeinism), which includes symptoms such as anxiety, agitation, insomnia, and gastrointestinal disorders. Recently, there has been increasing interest in the effect of caffeine consumption as a protective factor or risk factor for neurological and psychiatric disorders. Currently, the importance of personalized medicine is being emphasized, and research on sex/gender differences needs to be conducted. Our review focuses on the effect of caffeine consumption on several neurological and psychiatric disorders with respect to sex differences to provide a better understanding of caffeine use as a risk or protective factor for those disorders. The findings may help establish new strategies for developing sex-specific caffeine therapies.

Perfluoropolyether-benzophenone as a highly durable, broadband anti-reflection, and anti-contamination coating.

Anti-reflection and anti-contamination coatings prepared from fluorinated polymers have widespread and important applications, ranging from protective films for corrosion resistance to high-tech microelectronics and medical devices due to their transparency, low refractive index, stain resistance, and antifouling properties. However, the application of existing coatings is hindered by low surface adhesion to the target substrate and weakness when exposed to mechanical stress or damage, resulting in significant limitations to their practical applications. Herein, we incorporate perfluoropolyether (PFPE) with benzophenone (BP) to develop an efficient coating material (PFPE-BP) possessing broadband anti-reflectivity, anti-contamination properties, excellent abrasion resistance, and stability under elevated temperatures and relative humidity. The presence of BP allows the coating materials to be homogeneously mixed with a commercial hard coating solution to uniformly coat the target substrate. Furthermore, UV light irradiation on the coating surface results in excellent adhesion between BP groups of PFPE-BP and the hard coating matrix.

Fluorinated Titania Nanoparticle-Induced Piezoelectric Phase Transition of Poly(vinylidene fluoride).

We prepared F-coated rutile titanium dioxide nanoparticles (r-TiO2 NPs) via simple thermal annealing of titania NPs in poly(vinylidene fluoride) (PVDF) and demonstrated that the F-coated r-TiO2 NP-doped composite film could efficiently induce piezoelectric phase transition of non-electroactive PVDF due to highly electronegative F bonds on the surface of these NPs. In the case of a 2.0 wt % composite film, 99.20% of the non-electroactive PVDF was transformed into the electroactive phase. Additionally, utilizing the F-coated r-TiO2 NPs for a piezoelectric device led to an enhancement of the piezoelectric performance. With the 5.0 wt % composite film, the resulting piezoelectric device exhibited voltage generation of 355 mV, whereas a device with the innate r-TiO2 NPs exhibited voltage generation of only 137 mV. Furthermore, because of optical inactivity of F-coated r-TiO2 NPs, the piezoelectric films exhibited high stability under 64 h of photoirradiation at an intensity of 0.1 W/cm2. These results indicate that the F-coated r-TiO2 NP-doped composite films could be useful for various applications, including outdoor energy-harvesting, self-powered wearable devices, and portable sensors.

Solution-Processable Photonic Inks of Mie-Resonant Hollow Carbon-Silica Nanospheres.

Hollow carbon-silica nanospheres that exhibit angle-independent structural color with high saturation and minimal absorption are made. Through scattering calculations, it is shown that the structural color arises from Mie resonances that are tuned precisely by varying the thickness of the shells. Since the color does not depend on the spatial arrangement of the particles, the coloration is angle independent and vibrant in powders and liquid suspensions. These properties make hollow carbon-silica nanospheres ideal for applications, and their potential in making flexible, angle-independent films and 3D printed films is explored.

Preparation and electroactive phase adjustment of Ag-doped poly(vinylidene fluoride) (PVDF) films.

The crystallinities of Ag-doped poly(vinylidene fluoride) (PVDF) films were modified by removing Ag+ using a novel washing process, which allowed control of the ratio of γ- and ß-phases. The polarity of the composite film without Ag+ removal through the washing process reached 98%, and the ß-phase content in the total electroactive phase was increased to 61%, according to Fourier-transform infrared spectroscopy. When Ag+ were removed through a process involving several cycles of washing, filtering, drying, and re-dissolving, the highest ratio of the γ-phase was increased to 67%, 28% higher than that before washing. This showed that Ag+ induced ß-phase formation while Ag nanoparticles induced γ-phase formation, and that the ratio of γ- and ß-phases in PVDF composite films can be controlled to suit specific applications by this washing process.

A naked mole rat iPSC line expressing drug-inducible mouse pluripotency factors developed from embryonic fibroblasts.

Naked mole rats (NMRs, Heterocephalus glaber) are long-lived, cancer-resistant rodents. Here, we report the development of an induced pluripotent stem cell (iPSC) line generated from immortalized NMR embryonic fibroblasts transduced with a doxycycline-inducible mouse OSKM polycistronic vector. This iPSC line was shown to express pluripotency-associated markers, form embryoid bodies, differentiate in vitro to the derivatives of three germ layers, and exhibit normal karyotype. The ability of iPSCs to differentiate in vivo was supported by the contribution to interspecific chimera upon injection into mouse blastocysts. This NMR iPSC line may be a useful tool in cancer and aging research.

Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins.

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDP-glucose:glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vitro splenic B cell differentiation. However, Selenof knockout animals show neither enhanced bacterial killing capacity nor antigen-induced systemic IgM activity, suggesting that excess immunoglobulins are not functional. In addition, ER-to-Golgi transport of a target glycoprotein was delayed in Selenof knockout embryonic fibroblasts, and proteomic analyses revealed that Selenof deficiency is primarily associated with antigen presentation and ER-to-Golgi transport. Together, the data suggest that Selenof functions as a gatekeeper of immunoglobulins and, likely, other client proteins that exit the ER, thereby supporting redox quality control of these proteins.

Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera.

Naked mole rats (NMRs) are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs) from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.

Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo.

Post-translational redox modification of methionine residues often triggers a change in protein function. Emerging evidence points to this reversible protein modification being an important regulatory mechanism under various physiological conditions. Reduction of oxidized methionine residues is catalyzed by methionine sulfoxide reductases (Msrs). Here, we show that one of these enzymes, a selenium-containing MsrB1, is highly expressed in immune-activated macrophages and contributes to shaping cellular and organismal immune responses. In particular, lipopolysaccharide (LPS) induces expression of MsrB1, but not other Msrs. Genetic ablation of MsrB1 did not preclude LPS-induced intracellular signaling in macrophages, but resulted in attenuated induction of anti-inflammatory cytokines, such as interleukin (IL)-10 and the IL-1 receptor antagonist. This anomaly was associated with excessive pro-inflammatory cytokine production as well as an increase in acute tissue inflammation in mice. Together, our findings suggest that MsrB1 controls immune responses by promoting anti-inflammatory cytokine expression in macrophages. MsrB1-dependent reduction of oxidized methionine in proteins may be a heretofore unrecognized regulatory event underlying immunity and inflammatory disease, and a novel target for clinical applications.