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Abstract The mechanism of convective cell initiation and regeneration in the Bandung Basin ( $$107.35^\circ \text{E}-107.95^\circ \text{E};6.75^\circ \text{S}-7.25^\circ \text{S}$$ 107 . 35 ∘ E - 107 . 95 ∘ E ; 6 . 75 ∘ S - 7 . 25 ∘ S ), Indonesia, is investigated using a Weather Research and Forecasting model. Based on the Cumulative Distribution Function and Regeneration Index, model simulations were conducted using case studies in February–March 2019. Upslope wind flows to the mountain peak in north and south of the basin due to solar heating, carrying water vapor from the bottom of the basin. Therefore, low-level convergence is formed due to the convergence of winds from the bottom of the basin and from outside the basin. The low-level convergence causes the developing updraft, makes atmosphere unstable, and generates convective initiation. The convective system will be developed in the mountains region, produced precipitation, and formed cold pools on the surface. The cold pool will fall down the slopes and convective activity from the mountains will continue to the bottom of the basin. The convective system’s outflow causes the cold pool to move in the west–east direction. The cold pool will collide with warmer air from the opposite direction, resulting in an updraft at the cold pool leading edge, and convection will be re-initiated (convective regeneration) in the Bandung Basin, with the new convective system tending to move eastward.

Accelerating age at first calving (AFC) is a strategy for sustainable dairy farming, whereas the impact of a reduction in AFC on long-term performance remains unclear. In this study, longevity and milk productivity until the end of the third lactation period were investigated retrospectively according to AFC. A total of 169 cows were categorized according to AFC as young, moderate, old, and very old (< 22.5, 22.5 –< 24.0, 24.0 –< 25.5, and > 25.5 months). The young AFC group had approximately 70 kg lower body weight before first calving (620 vs. 695 kg, P < 0.05) and experienced their first calving approximately 4.2 months earlier than the very old AFC group (21.9 vs. 26.1 months, P < 0.05). The survival rate at the third calving stage was 61% in the young AFC group, which was higher than those in the moderate (42%), old (35%), and very old (33%) AFC groups. In the young AFC group, no cows were culled because of low productivity and hoof disease, compared to 5.0–8.1% of older AFC cows. The young AFC group had a higher overall lifetime milk yield (cumulative milk yield/days from birth to the end of final lactation) than the old AFC group (14.3 vs. 8.7 kg/d, P = 0.11). The cows that survived the third calving had better reproductive performance than non-surviving cows; however, no statistical difference was detected among the AFC groups. In conclusion, AFC as early as 22.5 months could be associated with better survivability and higher overall lifetime milk yield than older AFC without impairing reproductive performance. Our results suggest that accelerating AFC may lead to higher profitability.

Abstract Cross-equatorial northerly surge (CENS) is known to cause torrential rainfall over Java Island in the Maritime Continent. Some studies indicated that the rainfall increase is attributed to changes in the diurnal cycle of rainfall (DCR) in northwestern Java. It is not well understood whether the DCR changes are present in the other parts of Java Island and whether the changes are similar to those in northwestern Java. This study performs climatological analyses to investigate the regional variation of the influence of the CENS on the DCR over Java Island using IMERG and ERA5 data sets of 20 years of boreal winter. We find that there are differences in intensity, timing, and coverage of DCR responses over western, central, and eastern Java. CENS modifies the timing of coastal rainfall on the northern coast, resulting in early morning rainfall enhancement owing to the convergence between the incoming northerlies and land breeze. A small increase in early morning rainfall is observed in eastern Java, possibly due to the northerly flow gaining more zonal components on the eastern coast, which then results in relatively weaker convergence than the western coast. The timing of early morning rainfall appears to be slightly different between the three areas. CENS is also found to suppress afternoon rainfall inland because of increasing static stability due to cold air advection from the north. The suppression varies from western to eastern Java, with the largest suppression seen in western Java. Relatively narrower and wider suppression areas are found in central and eastern Java, respectively. These differences are attributed to the topography characteristics of Java.

Abstract A heavy rainfall event caused by mesoscale convective systems (MCSs) resulted in flooding over areas of Davao City in Mindanao Island, Philippines, on 03 May 2017. The event occurred during the summer season (April–May) under weak large-scale conditions. This study investigated the initiation and development of MCSs by performing high-resolution numerical simulations with the finest grid spacing of 200 m, using the Weather Research and Forecasting (WRF) model. It was found that the merging of two meso- $$\beta$$ β scale convective systems over the west and east of Mount Apo caused the flood-producing rainfall in the Davao area. Results show that the west meso- $$\beta$$ β scale convective system formed over the basin area in Mindanao Island due to moisture advection from sea breeze circulation. In addition, the concave geometry of the Mindanao basin assisted in accumulating moisture which made the basin favorable for convection development. Meanwhile, the precipitating downdrafts generated cold pools wherein the continuous convergence of multiple outflow boundaries resulted in the further development and maintenance of the MCS over the basin. While the east meso- $$\beta$$ β scale convective system developed over the Davao area due to the interaction between southeasterlies (ambient trade winds) and Mount Apo terrain. Merging of the MCSs resulted in the development of a larger meso- $$\beta$$ β scale system. Eventually, the larger meso- $$\beta$$ β scale convective system split and splitted MCSs weakened over time.

Although pregnant women’s fish consumption is beneficial for the brain development of the fetus due to the DHA in fish, seafood also contains methylmercury (MeHg), which adversely affects fetal brain development. Epidemiological studies suggest that high DHA levels in pregnant women’s sera may protect the fetal brain from MeHg-induced neurotoxicity, but the underlying mechanism is unknown. Our earlier study revealed that DHA and its metabolite 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) produced by cytochrome P450s (P450s) and soluble epoxide hydrolase (sEH) can suppress MeHg-induced cytotoxicity in mouse primary neuronal cells. In the present study, DHA supplementation to pregnant mice suppressed MeHg-induced impairments of pups’ body weight, grip strength, motor function, and short-term memory. DHA supplementation also suppressed MeHg-induced oxidative stress and the decrease in the number of subplate neurons in the cerebral cortex of the pups. DHA supplementation to dams significantly increased the DHA metabolites 19,20-epoxydocosapentaenoic acid (19,20-EDP) and 19,20-DHDP as well as DHA itself in the fetal and infant brains, although the expression levels of P450s and sEH were low in the fetal brain and liver. DHA metabolites were detected in the mouse breast milk and in human umbilical cord blood, indicating the active transfer of DHA metabolites from dams to pups. These results demonstrate that DHA supplementation increased DHA and its metabolites in the mouse pup brain and alleviated the effects of MeHg on fetal brain development. Pregnant women’s intake of fish containing high levels of DHA (or DHA supplementation) may help prevent MeHg-induced neurotoxicity in the fetus.

It has been suggested that domestication has turned cattle from seasonal breeders to annual breeders. This study examined the seasonal differences in early postpartum ovulation and subsequent reproductive performance in 542 Holstein cows. Cows displaying corpora lutea in the ovary at 26 days postpartum were defined as early ovulators. Factors affecting the occurrence of early ovulation were analyzed, and subsequent reproductive traits were compared between cows with and without early ovulation. During the summer season, 70.6% of calving cows showed early ovulation, whereas 48.7, 39.2, and 47.2% presented this condition in autumn, winter, and spring, respectively (P < 0.01). Third parity cows showed early ovulation more often than their first parity counterparts (P < 0.05). Cows with a 2.50 to 3.00 or > 3.00 body condition score (BCS) more frequently became early ovulators than those with BCSs < 2.50 (P < 0.01). Calving year was a risk factor, and uterine abnormalities were also often risk factors for early ovulation. The survival analysis showed that seasonal differences in the occurrence of early ovulation did not completely affect the time to first service and pregnancy. Proportional hazard regression analysis revealed that calving year, parity, and early ovulation were risk factors for the time to first service and that calving year was a risk factor for the time to pregnancy. In conclusion, domesticated dairy cows maintain seasonality in postpartum ovarian activity but not in subsequent fertility.

ABSTRACT: Dairy cattle must allocate energy to milk production and reproduction. Therefore, understanding the environmental factors that affect conception rates in nulliparous and primiparous cows is helpful in appropriate feeding management strategies before and after calving. Accordingly, the aim of this study was to investigate the influence of environmental factors before and after the first calving on the conception rate, representing the starting point of milk production. The records of the first artificial insemination (AI) from Holstein nulliparous cows (n = 533,672) and primiparous cows (n = 516,710) in Hokkaido, Japan, were analyzed using separate multivariable logistic regression models. The mean conception rates for nulliparous and primiparous cows from 2012 to 2018 were 55.2 and 39.2%, respectively. In both nulliparous and primiparous cows, the conception rate of crossbreeding using Japanese Black (JB) semen was significantly higher than that for purebred Holstein breeding. The conception rate using sexed semen decreased in the warmer months only in nulliparous cows. Moreover, we grouped primiparous cows according to milk yield during peak lactation (PY; < 25, 25–30, 30–35, ≥35 kg) and the interval from calving to first insemination (CFI; < 60, 60–79, 80–99, ≥100 d), and evaluated their combined effect on the conception rate. Both PY and CFI strongly affected the conception rate in primiparous cows, which decreased with an increase in PY, even for the group with CFI ≥100 d; however, the conception rate increased for a CFI ≥60 d regardless of PY. Taken together, this study demonstrates the long-term effect of PY and an independent effect of CFI on the conception rate of cows. These results provide guidance for management to execute appropriate AI implementation strategies before and after lactation.

Abstract Background Valproic acid (VPA) is a clinically used antiepileptic drug, but it is associated with a significant risk of a low verbal intelligence quotient (IQ) score, attention-deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. Prenatal VPA exposure has been reported to affect neurogenesis and neuronal migration and differentiation. In addition, growing evidence has shown that microglia and brain immune cells are activated by VPA treatment. However, the role of VPA-activated microglia remains unclear. Methods Pregnant female mice received sodium valproate on E11.5. A microglial activation inhibitor, minocycline or a CCR5 antagonist, maraviroc was dissolved in drinking water and administered to dams from P1 to P21. Measurement of microglial activity, evaluation of neural circuit function and expression analysis were performed on P10. Behavioral tests were performed in the order of open field test, Y-maze test, social affiliation test and marble burying test from the age of 6 weeks. Results Prenatal exposure of mice to VPA induced microglial activation and neural circuit dysfunction in the CA1 region of the hippocampus during the early postnatal periods and post-developmental defects in working memory and social interaction and repetitive behaviors. Minocycline, a microglial activation inhibitor, clearly suppressed the above effects, suggesting that microglia elicit neural dysfunction and behavioral disorders. Next-generation sequencing analysis revealed that the expression of a chemokine, C–C motif chemokine ligand 3 (CCL3), was upregulated in the hippocampi of VPA-treated mice. CCL3 expression increased in microglia during the early postnatal periods via an epigenetic mechanism. The CCR5 antagonist maraviroc significantly suppressed neural circuit dysfunction and post-developmental behavioral disorders induced by prenatal VPA exposure. Conclusion These findings suggest that microglial CCL3 might act during development to contribute to VPA-induced post-developmental behavioral abnormalities. CCR5-targeting compounds such as maraviroc might alleviate behavioral disorders when administered early.

Problem decomposition methods may help to overcome the size limitations of quantum hardware and allow largescale electronic structure simulations. Here, a method to simulate a ten-atom Hydrogen ring by decomposing it into smaller fragments that are amenable to a currently available trapped ion quantum computer is demonstrated experimentally.

The neurologic complications associated with the coronavirus disease 2019 (COVID-19) is becoming more prevalent in children after the appearance of the Omicron strain. An association between COVID-19 and posterior reversible encephalopathy (PRES) has been consistently reported in adults, but little information is available in the pediatric age group. There are only few case reports of COVID-19-related PRES in children, and all of these patients were either on some type of immunomodulatory medications or whose general condition was severe. The present case, a 9-year-old Japanese boy, who had no fever but vomited several times from days 1–4 of a COVID-19 infection had an afebrile seizure on the 8th day of his illness. The patient had no history of hypertension, and had not previously been administered any immunosuppressive drugs before or during the period of his COVID-19 infection. On admission, his physical findings were unremarkable, except for a high blood pressure. The results obtained by brain computed tomography and magnetic resonance imaging were consistent with PRES. The patient recovered with no sequelae after treatment with antihypertensive drugs. Further investigations did not suggest any underlying disease that could have caused the transient hypertension. Although PRES is relatively rare in children, pediatricians should keep in mind that this syndrome can be complicated, even in children with mild COVID-19 infections.

Lactic acid bacteria are commonly in the fermentation industry and pose potential positive effects on health. In this study, a new lactic acid bacterium was isolated from fermented vegetable extracts in Myoko, Niigata, Japan. This bacterium is fructophilic, acidophilic, and hard to grow on agar medium. The isolate is Gram-stain-positive, non-spore-forming, non-motile, rod-shaped, and catalase-negative. Growth occurred at pH 3.5–5.5, with optimal growth at pH 4.5–5.0. The cells formed colonies on a solid MRS medium with 20% (w/v) sucrose and 0.8% (w/v) gellan gum under anaerobic conditions. The bacterium was able to grow on up to 50% (w/v) sucrose but not on d-glucose. Moreover, 16S rRNA gene sequence analysis revealed that the strain was most closely related to Apilactobacillus ozensis (93.1% sequence similarity). The values of average nucleotide identity, digital DNA-DNA hybridization, average amino acid sequence identity, and amino acid identity of conserved genes were calculated between the isolated strain (type strain is WR16-4T = NBRC 115064T = DSM 112857T) and its phylogenetically closest type strains. The average nucleotide identity values (73.36–78.28%) and DNA-DNA hybridization values (16.3–32.9%) were significantly lower than the threshold values for species boundaries. The average amino acid sequence identity values (53.96–60.88%) were significantly below the threshold boundary of genus demarcation (68%). The amino acid identity of conserved genes values compared to strain WR16-4T were the genera Apilactobacillus, Nicoliella spurrieriana SGEP1_A5T, Acetilactobacillus jinshanensis HSLZ-75T, and Fructilactobacillus were 62.51–63.79%, 62.87%, 62.03%, and 58.00–61.04%, respectively. The 16S rRNA gene and core genome phylogenetic trees suggested that this novel strain was most closely related to the type strain of A. jinshanensis HSLZ-75T. Based on the physiological, morphological, and phenotypical characteristics of strain WR16-4T, we propose its classification as a novel genus, Philodulcilactobacillus myokoensis gen. nov., sp. nov.

Abstract To investigate future changes in snow cover and snowfall over mountainous areas in central Japan, we conducted regional climate projections using a high-resolution non-hydrostatic regional climate model (NHRCM) with 5 km and 1 km grid spacings. Boundary conditions are derived from the database for Policy Decision making for Future climate change (d4PDF) 20 km regional climate projections (d4PDF20). The d4PDF20 assumes two future climates when global mean surface air temperatures are approximately 2 K and 4 K warmer than in the preindustrial period. Experiments with 5 km grid spacing are conducted by NHRCM for 372 years in d4PDF20 in each climate. Experiments with 1 km grid spacing are performed focusing on 5 years with heavy, median, and light snow cover of mountainous areas in each climate. In the years with heavy snow cover in 2 K and 4 K warming climates, snowfall is enhanced from late December to February at more than 2000 m above sea level (mASL) in the northern parts of Japan’s Northern Alps, resulting in heavy snow cover comparable to that in the present climate. Heavy daily snowfall remarkably increases due to global warming in the years with heavy snow cover. At low elevations below 500 mASL, snowfall decreases in all ranges of snowfall intensity in the 4 K warming climate, while the frequency of heavy daily snowfall increases in the 2 K warming climate. Precipitation is enhanced around the Japan-Sea Polar-airmass Convergence Zone and the mountainous area facing the Sea of Japan, resulting in strengthened heavy snowfall at high elevations where the winter mean temperature is approximately − 10 °C in the present climate. On the other hand, remarkable reductions in snow cover and snowfall are projected in years with light snow cover. Our results indicate that global warming causes heavy and light mid-winter snowfalls at high elevations of Japan’s Northern Alps that are more extreme than those in the present climate. Graphical abstract

A reference electrode equipped with ionic liquid salt bridge consisting of tributyl(2-methoxyethyl)phosphonium bis(pentafluoroethanesulfonyl)amide has been employed for potentiometric precipitation titration of chloride with silver ions in water at 25 °C. A model for the titration curve was regressed to experimental curves, taking into account the change in the activity coefficients of relevant ionic species in the course of the titration, to obtain the least square estimates of two adjustable parameters in the model, the solubility product (Ksp) and the analyte concentration. The least-square estimate of Ksp, (1.840 ± 0.060) × 10−10, i.e., pKsp = 9.736 ± 0.014, is in good agreement with literature data, but with higher precision.

Objective Because lactation periods in dairy cows lengthen with increasing total milk production, it is important to predict individual productivities after 305 days in milk (DIM) to determine the optimal lactation period. We therefore examined whether the random regression (RR) coefficient from 306 to 450 DIM (M2) can be predicted from those during the first 305 DIM (M1) by using a RR model. Methods We analyzed test-day milk records from 85,690 Holstein cows in their first lactations and 131,727 cows in their later (second to fifth) lactations. Data in M1 and M2 were analyzed separately by using different single-trait RR animal models. We then performed a multiple regression analysis of the RR coefficients of M2 on those of M1 during the first and later lactations. Results The first-order Legendre polynomials were practical covariates of RR for the milk yields of M2. All RR coefficients for the additive genetic (AG) effect and the intercept for the permanent environmental (PE) effect of M2 had moderate to strong correlations with the intercept for the AG effect of M1. The coefficients of determination for multiple regression of the combined intercepts for the AG and PE effects of M2 on the coefficients for the AG effect of M1 were moderate to high. The daily milk yields of M2 predicted by using the RR coefficients for the AG effect of M1 were highly correlated with those obtained by using the coefficients of M2. Conclusion Milk production after 305 DIM can be predicted by using the RR coefficient estimates of the AG effect during the first 305 DIM.

Abstract Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic seizures; however, the molecular mechanism by which it achieves this effect is still largely unknown. DHA stimulates the retinoid X receptor, which reportedly regulates the expression of cytochrome P450 aromatase (P450arom). This study aimed to clarify how DHA suppresses seizures, focusing on the regulation of 17β-estradiol synthesis in the brain. Dietary supplementation with DHA increased not only the expression of P450arom, but also 17β-estradiol in the cerebral cortex. While DHA did not affect the duration or scores of the seizures induced by pentylenetetrazole, DHA significantly prolonged the seizure latency. A P450arom inhibitor, letrozole, reduced 17β-estradiol levels and completely suppressed the elongation of seizure latency elicited by DHA. These results suggest that DHA delays the onset of seizures by promoting the synthesis of 17β-estradiol in the brain. DHA upregulated the expression of anti-oxidative enzymes in the cerebral cortex. The oxidation in the cerebral cortex induced by pentylenetetrazole was significantly attenuated by DHA, and letrozole completely inhibited this suppressive action. Thus, the anti-oxidative effects of 17β-estradiol may be involved in the prevention of seizures mediated by DHA. This study revealed that 17β-estradiol in the brain mediated the physiological actions of DHA.

In spite of possessing desirable anticancer properties, currently, limited clinical success has been achieved with 20(S)-protopanaxadiol (aPPD) and 1,25-dihydroxyvitamin D3 (calcitriol). This study is designed to evaluate if the combination of aPPD with calcitriol can inhibit human prostate cancer xenograft growth by using nuclear receptor signaling. Athymic male nude mice were utilized to establish an androgen-independent human prostate cancer C4-2 cell castration-resistant prostate cancer (CRPC) xenograft model. Mice were treated orally for six weeks with 70 mg/kg aPPD administered once daily or three times per week with 4 µg/kg calcitriol or in combination or only with vehicle control. Contrary to our expectations, calcitriol treatment alone increased C4-2 tumor growth. However, the addition of calcitriol substantially increased aPPD-mediated tumor growth suppression (76% vs. 53%, combination vs. aPPD alone). The combination treatment significantly increased levels of cleaved caspase-3 apoptotic marker compared to vehicle-treated or aPPD-treated C4-2 tumors. The mechanistic elucidations indicate that tumor inhibition by the aPPD and calcitriol combination was accompanied by elevated vitamin D receptor (VDR) protein expression. In silico data suggest that aPPD weakly binds to the native LBD pocket of VDR. Interestingly, the combination of aPPD and calcitriol activated VDR at a significantly higher level than calcitriol alone and this indicates that aPPD may be an allosteric activator of VDR. Overall, aPPD and calcitriol combination significantly inhibited tumor growth in vivo with no acute or chronic toxic effects in the C4-2 xenograft CRPC nude mice. The involvement of VDR and downstream apoptotic pathways are potential mechanistic routes of antitumor effects of this combination.

Computed, high-resolution, spatial distributions of solvation energy and entropy can provide detailed information about the role of water in molecular recognition. While grid inhomogeneous solvation theory (GIST) provides rigorous, detailed thermodynamic information from explicit solvent molecular dynamics simulations, recent developments in the 3D reference interaction site model (3D-RISM) theory allow many of the same quantities to be calculated in a fraction of the time. However, 3D-RISM produces atomic-site, rather than molecular, density distributions, which are difficult to extract physical meaning from. To overcome this difficulty, we introduce a method to reconstruct molecular density distributions from atomic-site density distributions. Furthermore, we assess the quality of the resulting solvation thermodynamics density distributions by analyzing the binding site of coagulation Factor Xa with both GIST and 3D-RISM. We find good qualitative agreement between the methods for oxygen and hydrogen densities as well as direct solute-solvent energetic interactions. However, 3D-RISM predicts lower energetic and entropic penalties for moving water from the bulk to the binding site.

The accelerated progress in manufacturing noisy, intermediate-scale quantum (NISQ) computing hardware has opened the possibility of exploring its application in transforming approaches to solving computationally challenging problems. The important limitations common among all NISQ computing technologies are the absence of error correction and the short coherence time, which limit the computational power of these systems. Shortening the required time of a single run of a quantum algorithm is essential for reducing environment-induced errors and for the efficiency of the computation. We have investigated the ability of a variational version of adiabatic state preparation (ASP) to generate an accurate state more efficiently compared to existing adiabatic methods. The standard ASP method uses a time-dependent Hamiltonian, connecting the initial Hamiltonian with the final Hamiltonian. In the current approach, a navigator Hamiltonian is introduced which has a non-zero amplitude only in the middle of the annealing process. Both the initial and navigator Hamiltonians are determined using variational methods. A Hermitian cluster operator, inspired by coupled-cluster theory and truncated to single and double excitations/de-excitations, is used as a navigator Hamiltonian. A comparative study of our variational algorithm (VanQver) with that of standard ASP, starting with a Hartree–Fock Hamiltonian, is presented. The results indicate that the introduction of the navigator Hamiltonian significantly improves the annealing time required to achieve chemical accuracy by two to three orders of magnitude. The efficiency of the method is demonstrated in the ground-state energy estimation of molecular systems, namely, H _2 , P4, and LiH.

The cholesterol transfer function of StAR is uniquely integrated into adrenal cells, with mRNA translation and PKA phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol binding domain (CBD) initiates mitochondrial inter-membrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extra-mitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: SIK1 and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR mRNA molecules via dual hybridization at the 3’- and 5’ ends and reveals an unexpectedly high frequency of 1:1 pairing with mitochondria marked by the matrix StAR protein. This pairing may be central to translation-coupled cholesterol transfer. Altogether, our results show that adrenal cells exhibit high- efficiency StAR activity that needs to integrate rapid cholesterol transfer with homeostasis and pulsatile hormonal stimulation. StAR NBD, the extended 3.5kb mRNA, SIK1, and Tis11b play important roles.

BACKGROUND: Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. METHODOLOGY/PRINCIPAL FINDINGS: Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. CONCLUSIONS/SIGNIFICANCE: Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity.

BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21). METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of (3)H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

We are conducting a 5-km long-term atmospheric regional reanalysis for Japan with assimilating conventional observations (RRJ-Conv). RRJ-Conv is produced with a one-way double-nesting system consisting of a nonhydrostatic regional model and a local ensemble transform Kalman filter (LETKF), which is driven by the Japanese 55-year reanalysis (JRA-55). The assimilated data are limited to long-term available data, specifically surface in-situ pressure observations, upper-air radiosonde observations, and tropical cyclone center positions. This paper overviews the performance of RRJ-Conv for 20 years from July 2001 to June 2021, mainly focusing on precipitation and exploring added values to JRA-55. RRJ-Conv is confirmed to maintain long-term consistency of analysis quality. Compared to JRA-55, RRJ-Conv reduces biases in central pressures of tropical cyclones, maintaining position reproducibility. RRJ-Conv represents detailed spatial distributions of monthly precipitation, extreme values for daily precipitation, and their interannual variation more realistically than JRA-55. The improvements to JRA-55 are demonstrated for some extreme events, involving a tropical cyclone, Baiu front and East Asian winter monsoon. [ABSTRACT FROM AUTHOR]

We investigated the shape of the lactation curves of milk fatty-acid compositions and determined the optimal lactation curve function for each fatty-acid profile. The Hokkaido Dairy Milk Recording and Testing Association provided us with test-day records. We analyzed the proportion of de novo fatty acids per 100 g of raw milk, represented as DnM (%), the proportion of de novo fatty acids to total fatty acids, DnF (%), and the proportion of preformed fatty acids to total fatty acids, PrF (%). For DnM, we fitted polynomials ranging from the first to the fourth order, whereas the first to second-order Wilmink models were considered for DnF and PrF. The goodness of fit was assessed based on the mean error and mean squared error for each days in milk (DIM). DnM exhibited a slight increase as days in milk progressed. DnF increased up to DIM 126 and then decreased slightly. PrF declined until DIM 145 and then increased slightly. The optimal lactation curve function was determined to be the second-order polynomial for DnM and the first-order Wilmink model for DnF and PrF. The lactation curves for each calving age and month were similar to the single lactation curve estimated using the full data set, which included all individuals, for each trait. [ABSTRACT FROM AUTHOR]