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Maternal immune activation (MIA) in midpregnancy is a risk factor for neurodevelopmental disorders. Improper brain development may cause malformations of the brain; maldevelopment induced by MIA may lead to a pathology-related phenotype. In this study, a single intraperitoneal injection of 20 mg/kg polyriboinosinic–polyribocytidylic acid [poly(I:C)] was administered to C57BL/6J mice on embryonic day (E) 12.5 to mimic maternal viral infection. Histopathological analysis of neurogenesis was performed using markers for Pax6, Tbr2, and Tbr1. In these fetuses, significant increases were observed in the proportion of Pax6-positive neural progenitor cells and Pax6/Tbr2 double-positive cells 24 h after poly(I:C) injection. There were no differences in the proportion of Tbr1-positive postmitotic neurons 48 h after poly(I:C) injection. At E18.5, there were more Pax6-positive and Tbr2-positive neural progenitor cells in the poly(I:C)-injected group than in the saline-injected group. Gene ontology enrichment analysis of poly(I:C)-induced differentially expressed genes in the fetal brain at E12.5 demonstrated that these genes were enriched in terms including response to cytokine, response to decreased oxygen levels in the category of biological process. At E13.5, activating transcription factor 4 (Atf4), which is an effector of integrated stress response, was significantly upregulated in the fetal brain. Our results show that poly(I:C)-induced MIA at E12.5 leads to dysregulated neurogenesis and upregulates Atf4 in the fetal brain. These findings provide a new insight in the mechanism of MIA causing improper brain development and subsequent neurodevelopmental disorders.

Abstract We developed a non-destructive and rapid whole-mount bone staining method for small fish, Xenopus laevis, and rodent fetuses (RAP-B). RAP-B does not require skin or soft tissue removal. However, RAP-B requires hair removal from hairy animals, such as adult mice and rats. In the present study, we investigated hair removal chemical treatments that did not result in soft tissue destruction. The hair removal effectiveness was investigated using a calcium mercaptoacetate or sodium mercaptoacetate solution on skin fragments obtained from the back of adult mice. A mixture of 2% sodium mercaptoacetate in 3% potassium hydroxide was found to be the most effective in complete hair removal from the skin. Using this hair removal treatment as a pretreatment for RAP-B, the preparation of fast-acting artifact-free whole-mount bone staining was possible without skin and soft tissue removal (RAP-B/HR). We performed a seamless observation from a low magnification wide-view to a high magnification without artifactacting artifacts using fluorescence zoom microscopy. Therefore, the combination of RAP-B/HR and fluorescent zoom microscopy is a novel platform for three-dimensional, wide-field, high-resolution pathological anatomical analysis.

Acute tubulointerstitial nephritis (ATIN) can be caused by any number of factors, and it accounts for several percent of renal biopsy cases. In Japan, case reports exist, but there are few single-center series of ATIN cases. Case 1. A teenage male patient developed fever and cough on day X-61 and was found to have normal renal function and positive C-reactive protein (CRP) by his primary care physician. On day X-20, he presented with cough and nasal discharge in addition to low-grade fever, and his doctor noted renal dysfunction with serum creatinine of 2.12 mg/dL, negative urine occult blood, and positive urine glucose. Renal biopsy results showed diffuse interstitial nephritis with scarce glomerular involvement. There was no concurrent uveitis. Renal function normalized after 4 months of treatment with moderate-dose prednisolone. Cases 2–10. Of the 422 cases for which renal biopsies were performed at our institution from 2008 to 2021, acute tubulointerstitial nephritis was confirmed clinically and pathologically in 9 cases in addition to case 1, accounting for 2.4% of all biopsy cases. In the analysis of the 10 patients, the median age was 40 years old, eGFR at diagnosis was 19.4 (3.2–49.1) mL/min/1.73 m2, and 2 of them underwent hemodialysis, but both were weaned from dialysis, and the eGFR after treatment was 53.6 (20.8–110.0) mL/min/1.73 m2; all patients showed improvement (P

A tube-integrated flow sensor is proposed in this study by integrating a micro-electro mechanical systems (MEMS) flow-sensing element and electrical wiring structure on the same copper on polyimide (COP) substrate. The substrate was rolled into a circular tube with the flow-sensing element installed at the center of the tube. The signal lines were simultaneously formed and connected to the Cu layer of the substrate during the fabrication of the sensing structure, thus simplifying the electrical connection process. Finally, by rolling the fabricated sensor substrate, the flow sensor device itself was transformed into a circular tube structure, which defined the airflow region. By implementing several slits on the substrate, the sensing element was successfully placed at the center of the tube where the flow velocity is maximum. Compared to the conventional sensor structure in which the sensor was placed on the inner wall surface of the tube, the sensitivity of the sensor was doubled.

MC5R is known for its role in the exocrine function of sebaceous glands, but other functions in the epidermis remain unclear. This study focused on the relationship between MC5R and homeostasis in the epidermis and examined the role of MC5R in mice whose skin was irradiated with UVB waves. UVB irradiation-induced skin ulcers and severe inflammation at lower doses in homozygotes of MC5R-deficient (i.e., MC5R−/−) mice (150 mJ/cm2) than the doses in wild-type mice (500 mJ/cm2). Transepidermal water loss was increased (approximately 10-fold) in adult MC5R−/− mice compared with that in wild-type mice. In neonates, a dye exclusion assay showed no remarkable difference between MC5R−/− and wild-type mice. After UVB irradiation, compared with wild-type mice, MC5R−/− mice showed increased inflammatory cell infiltration in the dermis of the ulcerative region, significantly increased thickness of the epidermis in the nonulcerative region, significantly more prickle cells in the nonulcerative region, and increased serum IL-6 levels but decreased IL-10 levels. Transmission electron microscopy revealed fewer lamellar granules, less lipid secretion, and an expansion of the trans-Golgi network in the epidermis in MC5R−/− mice. This study elucidated the increased sensitivity to UVB irradiation and decreased barrier function in MC5R−/−mice.

Background: Maternal immune activation has been implicated in the pathophysiology of neurodevelopmental disorders such as autism spectrum disorders caused by maternal infection. It has been suggested that the placental origin of inflammatory cytokines leads to neurodevelopmental disorders. However, the identity of the initial immune-activated site in the placenta, in response to maternal viral infection, is not clear. Methods: By cross-breeding male enhanced green fluorescent protein (EGFP) transgenic mice with wild-type females, the placental tissues of maternal origin can be distinguished from those of paternal origin by EGFP expression. Using this method, at embryonic day (E) 12.5, dams were administered an intraperitoneal polyriboinosinic–polyribocytidylic acid (poly [I:C]) injection. We quantitatively analyzed the levels of phosphorylated interferon (IFN) regulatory factor 3 (pIRF3) in the placenta, and investigated the distribution of pIRF3 positive cells. Results: We show that maternally derived decidual cells are the initial target of maternal poly (I:C) through the toll-like receptor 3/TIR-domain-containing the adapter-inducing interferon-β signaling pathway. We also show that the expression of interferon-β was upregulated in the placenta after maternal injection with poly (I:C). Conclusion: These results suggest that maternally derived decidual cells are the initial target of maternal poly (I:C) and that this innate immune response is likely associated with a state of maternal immune activation.

We previously showed that maternal leukemia inhibitory factor (LIF) induces placental production of adrenocorticotropic hormone (ACTH), which stimulates fetal nucleated red blood cells to further secrete LIF and promote neurogenesis in rodent brains. However, the underlying mechanism of LIF-dependent ACTH induction remains unclear. Recently, we found that LIF induces corticotropin-releasing hormone (CRH) in mouse trophoblast stem cells. This finding supports the results of a previous study that CRH, which is produced by the placenta, induces placental ACTH production. In this study, we examined whether the effects of LIF are mediated by the induction of Pomc via CRH upregulation in mouse trophoblast. In vivo, protein levels of LIF and CRH peak in mouse placenta at 13.5 days post coitum. In mouse placenta, Crh mRNA and protein levels significantly increased 3 h after intraperitoneal injection of LIF (5 μg/kg body weight) into dams at 13.5 days post coitum. We also examined the effect of LIF-induced CRH on the expression of Pomc induced by LIF in mouse trophoblast stem cells in vitro. After LIF supplementation for 3 days, we found that the increased expression of Crh-induced by new supplementation of LIF was earlier than that of Pomc. Furthermore, LIF-induced upregulation of Pomc in mouse trophoblast stem cells was attenuated by inhibition of the CRH/CRHR1 pathway, whereas LIF-induced secretion of ACTH was attenuated by inhibition of the JAK/STAT3 pathway. Therefore, LIF indirectly increases placental Pomc expression through the CRH/CRHR1 pathway, and placental ACTH secretion is induced directly by LIF via the JAK/STAT3 pathway.

It is known that there is a universality behind pattern formation during phase separation induced by homogeneous quenching. However, this universality is broken when quenching is carried out in an inhomogeneous manner. An example is directional quenching, where a columnar or lamellar pattern may be formed depending on the speed of the quenching front. Despite the wide industrial and technological interest in pattern formation, the mechanism behind the formation of these columnar patterns is not yet understood. Here we investigated the dynamics of pattern formation induced by directional quenching using numerical simulations. We found that the interface of the first layer that is formed fluctuates, and a columnar pattern is formed when this fluctuation grows. In addition, we reveal that the effective confinement effect induced by the quenching front plays an important role in determining the nature of the fluctuations at the interface.

Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)-placental ACTH-fetal LIF signaling relay pathway (maternal-fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal-fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal-fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.