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During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development. The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.

Protein syntheses at appropriate timings are important for promoting diverse biological processes and are controlled at the levels of transcription and translation. Pou5f1/Oct4 is a transcription factor that is essential for vertebrate embryonic development. However, the precise timings when the mRNA and protein of Pou5f1/Oct4 are expressed during oogenesis and early stages of embryogenesis remain unclear. We analyzed the expression patterns of mRNA and protein of Pou5f1/Oct4 in mouse oocytes and embryos by using a highly sensitive in situ hybridization method and a monoclonal antibody specific to Pou5f1/Oct4, respectively. Pou5f1/Oct4 mRNA was detected in growing oocytes from the primary follicle stage to the fully grown GV stage during oogenesis. In contrast, Pou5f1/Oct4 protein was undetectable during oogenesis, oocyte maturation and the first cleavage stage but subsequently became detectable in the nuclei of early 2-cell-stage embryos. Pou5f1/Oct4 protein at this stage was synthesized from maternal mRNAs stored in oocytes. The amount of Pou5f1/Oct4 mRNA in the polysomal fraction was small in GV-stage oocytes but was significantly increased in fertilized eggs. Taken together, our results indicate that the synthesis of Pou5f1/Oct4 protein during oogenesis and early stages of embryogenesis is controlled at the level of translation and suggest that precise control of the amount of this protein by translational regulation is important for oocyte development and early embryonic development.

A set of sex chromosomes is required for gametogenesis in both males and females, as represented by sex chromosome disorders causing agametic phenotypes. Although studies using model animals have investigated the functional requirement of sex chromosomes, involvement of these chromosomes in gametogenesis remains elusive. Here, we elicit a germ cell-intrinsic effect of sex chromosomes on oogenesis, using a novel culture system in which oocytes were induced from embryonic stem cells (ESCs) harboring XX, XO or XY. In the culture system, oogenesis using XO and XY ESCs was severely disturbed, with XY ESCs being more strongly affected. The culture system revealed multiple defects in the oogenesis of XO and XY ESCs, such as delayed meiotic entry and progression, and mispairing of the homologous chromosomes. Interestingly, Eif2s3y, a Y-linked gene that promotes proliferation of spermatogonia, had an inhibitory effect on oogenesis. This led us to the concept that male and female gametogenesis appear to be in mutual conflict at an early stage. This study provides a deeper understanding of oogenesis under a sex-reversal condition.

This study aims to clarify the soil-structure interaction during earthquakes for an underground vertical shaft, which serve as an important facility of a nuclear power plant, constructed in a dense sand layer with a low groundwater level. To achieve this objective, numerical analyses were conducted to reproduce a series of centrifugal loading tests that included an unsaturated soil layer. Additionally, it was attempted to clarify the dynamic interaction between the soil and the structure, particularly focusing on the difference in lateral earth pressure exerted by the surrounding soil above and below the groundwater level. By conducting detailed investigations using three-dimensional effective stress analysis, the study confirmed the usefulness of this method for structural design in seismic conditions.

Hydrogen gas inhalation has not yet been elucidated to improve blood behaviors or antioxidant activity in blood. In the present study, the PEM (proton-exchange-membrane)-/platinum-plated electrode-equipped electrolyzer was examined as a hydrogen gas inhaler, which was estimated to supply 3% hydrogen as rapidly as post-operating 10–15 min, together with continuous 30 min retention of 20.8% oxygen being nearly equal to atmospheric oxygen contents. The 40 min inhalation of 3% hydrogen gas and thereafter 60 min rest were shown to enhance the antioxidant ability in human serum, as evaluated by ORAC (oxygen radical absorbing capacity)-based fluorometry, although scarcely enhanced for air dummy inhalation. Unexpectedly, antioxidant ability was 2.50-fold more enhanced for post-inhalational 0–60 min rest than during 40 min inhalation. Oxidative stress-suffering erythrocytes formed a rosary-chain-like aggregation composed of 3–6 cells, together with loss of a single hollow/biconcave-discoid structure in the cell central-part being necessary for erythrocyte passing through capillary vessels, both of which were prevented by 3% hydrogen gas inhalation. Hydrogen gas inhalation increased the intracellular foreign bodies, being distinguished from vacuole/cyst, in leucocytes, suggesting the hydrogen-activated leukocyte phagocytosis-associated events. Thus, 3%-hydrogen gas inhalation is suggested to potentially improve both the erythrocyte rheological/morphologic behaviors and the leucocyte phagocytosis-associated activity, concurrently with the enhanced antioxidant ability in blood.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is known to be the most common cause of dementia. We previously described the benefits of aromatherapy on the cognitive function of patients with AD utilizing various aromatic essential oils; however, its mechanism of action remains poorly understood. Consequently, in the present study, this mechanism was thoroughly evaluated employing a dementia mice model, specifically the senescence-accelerated mouse prone 8. The mice were exposed to a mixture of lemon and rosemary oil at nighttime as well as to a mixture of lavender and orange oil in the daytime for 2 months. The cognitive function of the mice was assessed before and after treatment with the aromatic essential oils using the Y-maze test. Moreover, the brain levels of amyloid beta (Aβ), abnormally phosphorylated tau, and brain-derived neurotrophic factor (BDNF) were measured following treatment. The benefits of aromatherapy on the cognitive function in mice were confirmed. It was also established that the brain levels of Aβ and abnormally phosphorylated tau were considerably lower in the aromatherapy group, while the levels of BDNF were marginally higher. These results suggest that aromatherapy employing these aromatic essential oils is beneficial for the prevention and treatment of AD.

A brief account of our recent work on the chemo-, regio- and stereoselective photocatalytic hydrogenolysis of allylic alcohols to alkenes promoted by palladium-loaded titanium oxide (Pd/TiO ) photocatalysts is presented. Since methanol is employed as the reducing agent, the method does not involve stoichiometric generation of salt waste. The photocatalytic hydrogenolysis proceeds at room temperature, and is compatible with the presence of functional groups such as C=C double bonds and hydroxyl groups at non-allylic positions. The regioselectivity is predictable: the hydrogen atom is predominantly incorporated into the sterically less hindered carbon atom of the allylic moiety. This protocol should provide straightforward green access to a range of platform chemicals (exemplified by the two-step synthesis of propylene from glycerol) and fine chemicals [e.g. ( )-(+)-lavandulol from ( )-(–)-carvone] without the need for protection/deprotection steps.

Determining how to apply hydrogen as a therapeutic/preventive antioxidant for oxidative-stress-related diseases practically in daily life has not been studied. The effects of bathtubs and buckets filled with hydrogen water (41 °C, >10 min bathing) were investigated on six subjects, without a medical prescription, suffering from skin roughness on the foot, hand, finger, or elbow. They were also treated with an electrolyzer composed of a lattice-shaped, microscopically flat, platinum-plated three-layer electrode, except for one subject who was treated with a micro-porous emittance terminal hydrogen-jetting apparatus, resulting in improvements in both cases. For another subject with similar skin roughness on both hands, immersing the right hand in an electrolytically generated hydrogen water bucket showed more marked improvement than immersing the left hand in a bucket with normal water. The nano-bubbles (average, mode, and median sizes of 157 nm, 136 nm, and 94 nm, respectively) increased 3.79 fold to 2.20 × 108/mL after 30 min electrolysis with 2 L of tap water and were boiling (98 °C, 2 min)-resistant, with heat stability in nano-bubbles as small as 69–101 nm, as evaluated by laser-beam-based Brownian movement trailing Nano-Sight analysis. The marked increase in nano-bubbles caused by electrolysis correlated with an increase in dissolved hydrogen (<15 μg/L to 527 μg/L) but not a decrease in dissolved oxygen (9.45 mg/L to 6.94 mg/L). Thus, the present study proposed the novelty of hydrogen regarding its contribution to health from the perspective that hydrogen-nano-bubble-rich water in a foot bucket, which was additively used together with a conventional bathtub and can be frequently used in daily life, improved diverse types of skin roughness.

During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins: meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase.

This study aimed to identify gut microbiota-derived metabolites governing the activity of hepatic CYP3A in blood level. Indole propionic acid (IPA) and lithocholic acid, ligands of the pregnane X receptor, a transcriptional regulator of CYP3A, and various gut microbiota-derived metabolites in blood level were analyzed. Results revealed that IPA and lithocholic acid did not affect CYP3A activity, while indoxyl sulfate (IS), a uremic toxin, affected CYP3A across different cell lines. The effects of IS on primary hepatocytes from three donors were analyzed, and a concentration-dependent impact was observed, as the CYP3A activity decreased in one donor and increased in another. These findings offer initial insights into blood-level gut microbiota-derived metabolites influencing hepatic CYP3A. Furthermore, the study demonstrates that the response to IS, beyond its concentration, can cause variations in hepatic CYP3A activity among individuals. This study advocates accounting for the dual effects of IS and the benefits of personalized medicine.