Context: Aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional ...differentiation of human adrenocortical cells. Little is known, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions.
Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other.
Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster, and a CYP11B1-expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing’s syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system.
Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.
Immunohistochemistry for human CYP11B2 and -B1 reveals a variegated zonation in the normal adrenal cortex, in addition to the conventional zonation, and may provide a pathological confirmatory diagnosis of adrenocortical tumors.
Docosahexaenoic acid (DHA) has been shown to have neuroprotective effects in Parkinson's disease, but the underlying mechanism has not been fully elucidated. DHA is metabolized to DHA epoxides (EDPs) ...and hydroxides by cytochrome P450s (P450s), and EDPs are further hydroxylated to the corresponding diols, dihydroxydocosapentaenoic acids (DHDPs) by soluble epoxide hydrolase (sEH). In the present study, we investigated the roles of these DHA metabolites in the beneficial effects of DHA supplementation on a rotenone-induced rat model of Parkinson's disease. Metabolite analysis by LC-MS revealed that CYP2A1, 2C11, 2C13, 2C23, and 2E1 contributed to the formation of EDPs, and these P450s and sEH were expressed in the rat brain. We found that DHA supplementation in rats improved the motor dysfunction induced by rotenone. In addition, DHA reversed the decrease in tyrosine hydroxylase and the increase in lipid peroxidation generated by rotenone in the striatum. DHA supplementation also induced mRNA expression of antioxidant genes, such as sod1 and catalase, and Nrf2 protein expression in the striatum. However, these effects of DHA supplementation were eliminated by cosupplementation with the sEH inhibitor TPPU. Supplementation with DHA increased the amount of 19,20-DHDP in the rat brain, while the amount of EDPs was not significantly increased. In addition, TPPU suppressed the increase in DHDPs and increased EDPs in the brain. In PC12 cells, 19,20-DHDP increased the mRNA levels of sod1 and catalase along with Nrf2 induction. This study suggests that DHA metabolites—DHDPs generated by P450s and sEH—have an important role in improving rotenone-induced Parkinson's disease.
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•・sEH inhibitor abrogated beneficial effects of DHA intake in Parkinson's model rats.•・DHA supplementation increased DHA metabolites by P450 and sEH, DHDPs, in the brain.•・19,20-DHDPs increased Nrf2-regulating antioxidant genes.
The CCDC26 gene is considered to encode a functional noncoding RNA associated with acute myeloid leukemia and other cancers. However, investigations into the physiological roles of CCDC26 are rare. ...Previously, we reported that CCDC26 regulated proliferation and cell death of leukemia cells through KIT, a receptor tyrosine kinase, by using K562 leukemia cells and their derivative CCDC26-knockdown (KD) cells. Here we propose a new role of CCDC26 in the differentiation of erythroid cells. We showed that expression of embryonic (ε- and ζ-) globins was markedly upregulated in CCDC26-KD cells compared with K562 control cells during hemin-induced differentiation. In contrast, expression of fetal-type γ-globin, a major globin expressed in original K562 cells, was decreased. These changes in the expression of globin genes mainly took place at the transcriptional level, with significant suppression of transcription of adult (β-, δ-) globins in CCDC26-KD cells. Re-introduction of exogenous CCDC26 into the CCDC26-KD cells recovered low-level expression of the embryonal globins. These results suggest CCDC26 has a role in switching transcription of globin genes in the differentiation of erythroid cells. The expression profile of the CCDC26-KD cells and control cells suggests FOG-2, a transcriptional modulator, as a candidate for a mediator of the CCDC26-associated regulation. We showed that both embryonic globins were transcriptionally activated in FOG-2-KD K562 cells. The KIT inhibitor ISCK03 suppressed the production of hemoglobin in K562 cells but did not affect transcription of globin genes. To summarize, FOG-2, but not KIT, is responsible for globin transcriptional regulation by CCDC26.
•The knockdown of a lncRNA, CCDC26, resulted in upregulated embryonic globin genes.•The knockdown of CCDC26 resulted in downregulation of fetal globin genes.•KIT was involved in the regulation of translation of globins, not transcription.•FOG-2 mediated switching between fetal and embryonic globin genes by CCDC26.
•Effects of LEV, VPA and CBZ on microglia were examined in vivo and in vitro.•LEV suppressed spontaneous recurrent seizures after status epilepticus.•LEV attenuated phagocytic microglia and ...neuroinflammation.•VPA partially suppressed neuroinflammation, and CBZ showed no effect.•LEV might suppress the seizures by suppression of microglial phagocytosis.
We previously reported that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam (DZP) prevents the development of spontaneous recurrent seizures. LEV suppresses increased expression levels of proinflammatory mediators during epileptogenesis after SE, but how LEV acts in neuroinflammatory processes is not yet known. In this study, we examined the effects of LEV on neuroinflammation and phagocytic microglia in vivo and in vitro and compared the effects of LEV with those of representative antiepileptic drugs valproate (VPA) and carbamazepine (CBZ). Repeated treatment with LEV for 30 days after the termination of pilocarpine-induced SE by DZP almost completely prevented the incidence of spontaneous recurrent seizures, while administration of VPA or CBZ showed no effect on the seizures. LEV clearly suppressed phagocytosis of mononuclear phagocytes, and cytokine expression was observed 2 days after SE. VPA attenuated neuroinflammation only, and CBZ showed no effect on changes after SE. Treatment with LEV significantly suppressed BV-2 microglial activation, which was defined by morphological changes, phagocytic activity and cytokine expression. By contrast, VPA and CBZ did not affect BV-2 microglial activity. In summary, LEV directly suppresses excess microglial phagocytosis during epileptogenesis, which might prevent the occurrence of spontaneous recurrent seizures after SE.
On the basis of lattice simulations using highly improved staggered quarks for twelve-flavor QCD with several bare fermion masses, we observe a flavor-singlet scalar state lighter than the pion in ...the correlators of fermionic interpolating operators. The same state is also investigated using correlators of gluonic interpolating operators. Combined with our previous study that showed twelve-flavor QCD to be consistent with being in the conformal window, we infer that the lightness of the scalar state is due to infrared conformality. This result shed some light on the possibility of a light composite Higgs boson ("technidilaton") in walking technicolor theories.
Abstract
Quantum computers have the potential to advance material design and drug discovery by performing costly electronic structure calculations. A critical aspect of this application requires ...optimizing the limited resources of the quantum hardware. Here, we experimentally demonstrate an end-to-end pipeline that focuses on minimizing quantum resources while maintaining accuracy. Using density matrix embedding theory as a problem decomposition technique, and an ion-trap quantum computer, we simulate a ring of 10 hydrogen atoms without freezing any electrons. The originally 20-qubit system is decomposed into 10 two-qubit problems, making it amenable to currently available hardware. Combining this decomposition with a qubit coupled cluster circuit ansatz, circuit optimization, and density matrix purification, we accurately reproduce the potential energy curve in agreement with the full configuration interaction energy in the minimal basis set. Our experimental results are an early demonstration of the potential for problem decomposition to accurately simulate large molecules on quantum hardware.
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.
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-
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-
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-
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-
β
scale system. Eventually, the larger meso-
β
scale convective system split and splitted MCSs weakened over time.
Highlights • Cultured astrocytes have more tolerance to MeHg toxicity than neuronal cells. • Astrocytes synthesize and release NGF and BDNF in response to MeHg. • NGF and BDNF signaling attenuates ...MeHg toxicity in neuronal cells. • NGF and BDNF from astrocytes could confer MeHg tolerance on neuronal cells.
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