Maternal immunoglobulin G affects brain development of mouse offspring.

Maternal immunoglobulin (Ig)G is present in breast milk and has been shown to contribute to the development of the immune system in infants. In contrast, maternal IgG has no known effect on early childhood brain development. We found maternal IgG immunoreactivity in microglia, which are resident macrophages of the central nervous system of the pup brain, peaking at postnatal one week. Strong IgG immunoreactivity was observed in microglia in the corpus callosum and cerebellar white matter. IgG stimulation of primary cultured microglia activated the type I interferon feedback loop by Syk. Analysis of neonatal Fc receptor knockout (FcRn KO) mice that could not take up IgG from their mothers revealed abnormalities in the proliferation and/or survival of microglia, oligodendrocytes, and some types of interneurons. Moreover, FcRn KO mice also exhibited abnormalities in social behavior and lower locomotor activity in their home cages. Thus, changes in the mother-derived IgG levels affect brain development in offsprings.

Natural Compounds with BMI1 Promoter Inhibitory Activity from Mammea siamensis and Andrographis paniculata.

A new coumarin derivative (1) and 30 known compounds were isolated from Mammea siamensis and Andrographis paniculata, guided by B cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) promoter inhibitory activity. Among the isolated compounds, 15 compounds showed BMI1 promoter inhibitory activity, and five compounds were found to be cytotoxic. 14-Deoxy-11,12-dehydroandrographolide (18) was highly cytotoxic to DU145 cells with an IC50 value of 25.4 µM. Western blotting analysis of compound 18 in DU145 cells suggested that compound 18 suppresses BMI1 expression.

The effect of spatially restricted experience on extrapolating learned views in desert ants, Melophorus bagoti.

Desert ants are known for learning walks at the beginning of their foraging life, during which they learn terrestrial cues of the panorama and surrounding landmarks around their nest. Foragers retain memories of the visual cues of the nest panorama learned during the pre-foraging trials. When away from the nest, they can compare these stored views with their current vision to return to their nest. In this study we investigated whether spatially restricted foraging ants can extrapolate their memory of visual cues to unexperienced sites. We carried out two conditions to examine whether desert ants extrapolate learned views. In the first condition, naïve ants of Melophorus bagoti were restricted to a nest arena 1 m in radius with a 10 cm high wall (wall condition) for 3 days, then released at distant locations on the fourth day and focal individuals return trips were recorded. In the second condition, a 10 cm sunken metallic barrier was constructed around the nest (moat condition) and the restricted foragers that viewed the unrestricted visual panorama around the 1 m-radius nest arena were then displaced away from the nest as in the wall condition. In the wall condition, most of the ants were unable to orient in the correct heading towards the home direction. In the moat condition ants were able to correctly orient to the nest from displacement sites up to 8 m from the nest. We conclude that while travelling to unfamiliar sites, M. bagoti ants can extrapolate views learned from foraging in a restricted area when given unrestricted views.

Alteration of parvalbumin expression and perineuronal nets formation in the cerebral cortex of aged mice.

Aging is associated with decline in cognitive function, but the underlying mechanisms have not been elucidated. Normal activity of pyramidal cells and parvalbumin-expressing interneurons (PV neurons) is essential for cognitive function. PV neurons participate in the regulation of pyramidal-cell firing. Abnormal function of PV neurons may occur with aging. We analyzed the density and the percentage of PV neurons surrounded by perineuronal nets (PNNs) in the entire cortex of adult (3-month-old) and aged (24-month-old) mice. PNNs are extracellular matrix molecules that cover PV neurons and control synaptic plasticity. PV-neuron density decreased in some cortical areas of aged compared to adult mice. In particular, in the retrosplenial granular cortex (RSG) of aged mice, pyramidal cells expressed PV protein at high levels. This study suggests that the RSG of aged mice is in an abnormal activated state. RSG function abnormality may be part of the cognitive decline mechanism.

Diffusion-based single-shot diffraction tomography.

Holographic microscopy is a powerful technique for noninvasive label-free biomedical imaging. Most holographic methods utilize reference light and/or multiple measurements to observe both the amplitude and phase of a light wave passing through a specimen. However, such fundamental requirements degrade the spatial resolution due to the use of a reference carrier, cause difficulties for real-time imaging of dynamic biological events, and make the optical setups bulky. Here, we realized reference-free, single-shot holographic tomography by just inserting a diffuser into the optical path in a conventional microscope setup to generate randomly structured illumination. A three-dimensional complex amplitude field was reconstructed from a single scattered intensity image by means of sparsity-constrained multislice phase retrieval.

Enantioselective Acyl Migration Reactions of Furanyl Carbonates with Chiral DMAP Derivatives.

An efficient enantioselective acyl migration reaction of furanyl carbonates was developed to construct all-carbon quaternary stereogenic centers. In some cases, the reactions required only 0.05 mol % (minimum 500 ppm) of catalyst and showed a high turnover frequency value (TOF; 3640 h-1 ). Multigram-scale reactions (10 grams) also proceeded with high enantioselectivity (>99:1 e.r.) in quantitative yield. The catalyst was robust and easily recovered in 98 % yield. A wide range of functional groups were tolerated (15 examples, >98 % yield, up to >99:1 e.r.), and a variety of optically active 3,3'-disubstituted benzofuranone derivatives, which are useful intermediates for the synthesis of natural products and pharmaceuticals, were efficiently obtained. Control experiments on the catalyst structure (e.g., catalyst 1 a vs. 1 a' and 1 a'') and computational calculations revealed that both the catalytic activity and enantioselectivity should be enhanced by hydrogen bonding between catalyst and substrate. Moreover, this system was applied to the challenging γ-selective acyl migration reaction of furanyl carbonates with high γ-selectivity and high enantioselectivity (α:γ=10:90, 95:5 e.r.).

A prospective observational study of immune reconstitution following transplantation with post-transplant reduced-dose cyclophosphamide from HLA-haploidentical donors.

Allogeneic hematopoietic cell transplantation (HCT) from HLA-haploidentical donors with post-transplantation high-dose cyclophosphamide (PT/Cy-haplo) now predominates worldwide. However, to our knowledge, no prospective study has compared immune reconstitution after PT/Cy-haplo with that after conventional HCT. The mechanism by which chronic graft-versus-host disease (GVHD) is inhibited by PT/Cy-haplo also remains unknown. We prospectively compared immune recovery patterns of lymphocyte subsets among four groups of adult patients with hematological disease who received HCT from either HLA-matched related or HLA-matched unrelated donors, cord blood transplantation, or reduced-dose PT/Cy-haplo. Counts of CD4+ T-cell subsets, CD8+ T-cell subsets, and NK cells on days 30 and 60 were often lower in PT/Cy-haplo than those in HLA-matched related HCT. The immune recovery pace in PT/Cy-haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T-cell (Tcon) ratio was significantly higher until day 90 in PT/Cy-haplo. In multivariate analysis, a higher Tregs-to-Tcon ratio on day 60 was significantly associated with a lower incidence of chronic GVHD (P < 0.01). The preservation of Tregs by PT/Cy in the early phase might have resulted in a lower incidence of chronic GVHD.

Desymmetrization of meso-1,2-Diols by a Chiral N,N-4-Dimethylaminopyridine Derivative Containing a 1,1'-Binaphthyl Unit: Importance of the Hydroxy Groups.

We developed an acylative desymmetrization of meso-1,2-diols using a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1h with tert-alcohol substituents. The reaction proceeds with a wide range of acyclic meso-1,2-diols and six-membered-ring meso-1,2-diols to provide a monoacylate selectively with a high enantiomeric ratio (er). Only 0.1 mol % of the catalyst facilitated the reaction within a short reaction time (3 h) to afford enantio-enriched monoacylated products in moderate to good yield. Several control experiments revealed that the tert-alcohol units of catalyst 1h play a significant role in achieving high catalytic activity, chemoselectivity of monoacylation, and enantioselectivity.

Decrease of lactogenic hormones induce epithelial-mesenchymal transition via TGFß1 and arachidonic acid during mammary gland involution.

During mammary gland involution, the epithelial mesenchymal transition (EMT) process plays an important role in tissue remodelling and in the termination of milk production. Transforming growth factor ß (TGFß) has been known as a central inducer to EMT and contributor to the mammary gland involution. However, the whole mechanism has accomplished the EMT process in mammary gland is still unclear. Here, we show that arachidonic acid, one of the major products in milk, is new player to control the EMT together with TGFß during mammary gland involution. Firstly, we observed decrease in CDH1 (epithelial marker gene) expression and increases in VIM and TWIST1 (mesenchymal marker genes), TGFB1, and PLCG2 (arachidonic acid synthesis gene) at involution. In epithelial cells culture experiments, depletion of lactogenic hormones to mimic the involution induced TGFß1 and PLCG2 expressions. Treatment with arachidonic acid in epithelial cells increased VIM and TWIST1 expressions without decrease of CDH1 expression, while TGFß1 decreased CDH1 and increased VIM and TWIST1; more importantly, TGFß1 induced the expression of PLCG2, but arachidonic acid did not induce the expression of TGFB1. Finally, arachidonic acid accelerated the TGFß1 increasing VIM and TWIST1 expressions, meanwhile arachidonic acid synthase inhibitor partially blocked the TGFß1 increasing VIM and TWIST1 expressions. In conclusion, TGFß1 stimulates arachidonic acid synthesis and the arachidonic acid has a function to postulate the EMT process together with TGFß1 during mammary gland involution.

Lactogenic hormone stimulation and epigenetic control of L-amino acid oxidase expression in lactating mammary glands.

L-amino acid oxidase (LAO), a classic flavoprotein, shows antibacterial activity by producing hydrogen peroxide. LAO exists in many tissues such as salivary gland, thymus, spleen, small intestine and testis. In particular, LAO was highly expressed in mice milk and plays an important factor in innate immunity of mammary glands. However, the mechanism which LAO expression is regulated spatially and temporally in lactating mammary glands has been unclear. In this study, we showed the contribution of lactogenic hormone and epigenetic control on LAO gene expression. In monolayer of mammary epithelial cells, treatment of lactogenic hormone mixture, dexamethasone, insulin and prolactin, did not induce LAO mRNA expression and its promoter activity, even though one of milk protein ß-casein expression was stimulated. However, increase of LAO expression was observed when the cells were treated with lactogenic hormones in a 3-dimensional culture. The results of chromatin immunoprecipitation analysis revealed that histone H3K18 acetylation increased and histone H3K27 tri-methylation decreased with lactation, which is associated with a period of high LAO expression. Moreover, the treatment of histone methylation inhibitor (DZNep) as well as histone deacetylation inhibitor (Trichostatine A) induced LAO expression in monolayer of mammary cells. Taken together, this is the first demonstration showing that LAO expression is induced in cell culture, and stimulation of lactogenic hormone and change of histone modification are promising signals to show highly expression of LAO in lactating mammary glands.

Effects of an extended photoperiod on gonadal function and condition of hair coats in Thoroughbred colts and fillies.

The effects of an extended photoperiod (EP) in Thoroughbreds colts and fillies from winter at one year old to spring at two years old on the gonadal functions, coat condition, and endocrine changes were investigated. Sixty-two Thoroughbreds (31 colts and 31 fillies) reared in the Hidaka Training and Research Center (Hidaka), Japan Racing Association were used. Thirty of them (15 colts and 15 fillies) were reared under EP conditions from December 20 to April 10, and the remaining 32 horses were reared under natural light alone as a control group. For EP, a 100-watt white bulb was set near the ceilings of stalls, and lighting conditions of 14.5-hr light and 9.5-hr dark periods were established. Blood was collected from the jugular vein once a month from October at one year old to February at two years old in both colts and fillies, and then twice a month in colts and weekly in fillies after March, and the coat condition was evaluated in January and April in 56 horses. To investigate endocrine changes, the plasma concentrations of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), immunoreactive (ir-) inhibin, testosterone, estradiol-17ß and progesterone were measured. No significant difference was noted in the coat condition between the two groups in January, but they changed from winter to summer coats (molting of winter coats) in April in the EP group compared with the control group. Regarding endocrine changes, the plasma concentrations of prolactin, FSH, ir-inhibin and testosterone were significantly higher in the EP colts than in the control group from January to April. The plasma concentrations of LH tended to rise in the EP colts from January to April compared with the control group. In the EP fillies, the plasma concentrations of prolactin, LH, ir-inhibin, estradiol-17ß and progesterone were significantly higher during January and April, but a significantly high level of FSH was noted in the control than EP group in January. The ovulation day was advanced in the EP fillies compared with the control group. The present study clearly demonstrated that EP treatment during rearing advanced the molting of winter coats in both colts and fillies. These results suggested to be due to the action of prolactin being increased by EP treatment. In addition, EP treatment stimulated the hypothalamus-pituitary-gonadal axis even in yearlings, and advanced ovulation in fillies. Since EP treatment-induced changes in the yearlings were within the physiological range, and the method is safe and simple, EP treatment may be an effective technique in horse husbandry.

New biflavonoids isolated from Xylia kerrii leaves extract with selective cytotoxicity against MH7A human rheumatoid arthritis synovial fibroblast cells.

Three new biflavonoids (1-3) and two known flavonoids (4, 5) were isolated from Xylia kerrii collected in Thailand. Compounds 1-5 showed selective cytotoxicity against the rheumatoid fibroblast-like synovial MH7A cell line, and these compounds showed weak cytotoxicity against the human lung synovial fibroblast WI-38 VA13 sub 2 RA cell line. Notably, compound 1 was highly selective toward MH7A cells with an IC50 value of 6.9 µM, whereas the IC50 value for WI-38 VA13 sub 2 RA cells was > 100 µM. The western blotting analysis of MH7A cells treated with compound 1 showed increased CDKN2A /p16INK4A and caspase-8 levels.

Activation of prefrontal parvalbumin interneurons ameliorates working memory deficit even under clinically comparable antipsychotic treatment in a mouse model of schizophrenia.

One of the critical unmet medical needs in schizophrenia is the treatment for cognitive deficits. However, the neural circuit mechanisms of them remain unresolved. Previous studies utilizing animal models of schizophrenia did not consider the fact that patients with schizophrenia generally cannot discontinue antipsychotic medication due to the high risk of relapse. Here, we used multi-dimensional approaches, including histological analysis of the prelimbic cortex (PL), LC-MS/MS-based in vivo dopamine D2 receptor occupancy analysis for antipsychotics, in vivo calcium imaging, and behavioral analyses of mice using chemogenetics to investigate neural mechanisms and potential therapeutic strategies for working memory deficit in a chronic phencyclidine (PCP) mouse model of schizophrenia. Chronic PCP administration led to alterations in excitatory and inhibitory synapses, specifically in dendritic spines of pyramidal neurons, vesicular glutamate transporter 1 (VGLUT1) positive terminals, and parvalbumin (PV) positive GABAergic interneurons located in layer 2-3 of the PL. Continuous administration of olanzapine, which achieved a sustained therapeutic window of dopamine D2 receptor occupancy (60-80%) in the striatum, did not ameliorate these synaptic abnormalities and working memory deficit in the chronic PCP-treated mice. We demonstrated that chemogenetic activation of PV neurons in the PL, as confirmed by in vivo calcium imaging, ameliorated working memory deficit in this model even under clinically comparable olanzapine treatment which by itself inhibited only PCP-induced psychomotor hyperactivity. Our study suggests that targeting prefrontal PV neurons could be a promising therapeutic intervention for cognitive deficits in schizophrenia in combination with antipsychotic medication.

Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome.

Down syndrome (DS) results from trisomy of human chromosome 21 (HSA21), and DS research has been conducted by the use of mouse models. We previously generated a humanized mouse model of DS, TcMAC21, which carries the long arm of HSA21. These mice exhibit learning and memory deficits, and may reproduce neurodevelopmental alterations observed in humans with DS. Here, we performed histologic studies of the TcMAC21 forebrain from embryonic to adult stages. The TcMAC21 neocortex showed reduced proliferation of neural progenitors and delayed neurogenesis. These abnormalities were associated with a smaller number of projection neurons and interneurons. Further, (phospho-)proteomic analysis of adult TcMAC21 cortex revealed alterations in the phosphorylation levels of a series of synaptic proteins. The TcMAC21 mouse model shows similar brain development abnormalities as DS, and will be a valuable model to investigate prenatal and postnatal causes of intellectual disability in humans with DS.

ILF3 prion-like domain regulates gene expression and fear memory under chronic stress.

The prion-like domain (PrLD) is a class of intrinsically disordered regions. Although its propensity to form condensates has been studied in the context of neurodegenerative diseases, the physiological role of PrLD remains unclear. Here, we investigated the role of PrLD in the RNA-binding protein NFAR2, generated by a splicing variant of the Ilf3 gene. Removal of the PrLD in mice did not impair the function of NFAR2 required for survival, but did affect the responses to chronic water immersion and restraint stress (WIRS). The PrLD was required for WIRS-sensitive nuclear localization of NFAR2 and WIRS-induced changes in mRNA expression and translation in the amygdala, a fear-related brain region. Consistently, the PrLD conferred resistance to WIRS in fear-associated memory formation. Our study provides insights into the PrLD-dependent role of NFAR2 for chronic stress adaptation in the brain.

Non-occlusive mesenteric ischemia during acute stroke management: three case reports.

BACKGROUND: There are many reports of non-occlusive mesenteric ischemia in patients on maintenance hemodialysis and following cardiac surgery. However, there are few reports of non-occlusive mesenteric ischemia in patients with acute stroke. CASE PRESENTATION: We report three cases of non-occlusive mesenteric ischemia with onset during treatment for acute stroke. All of the patients were undergoing strict blood-pressure control, and two patients developed NOMI soon after tracheostomy when enteral nutrition had been resumed. CONCLUSION: Many stroke patients are older adults with risk factors such as arteriosclerosis. Thus, during acute stroke management, there is a possibility that patients may develop non-occlusive mesenteric ischemia due to decreased intestinal blood flow secondary to strict blood-pressure control. This case report implicates early enteral nutrition as a potential etiopathogenic factor of non-occlusive mesenteric ischemia in patients with acute stroke.

Giant splenic artery aneurysm rupture into the stomach that was successfully managed with emergency distal pancreatectomy.

BACKGROUND: Splenic artery aneurysms usually rupture into the free peritoneal space and rarely into the gastrointestinal tract. We report the case of a patient with a giant splenic artery aneurysm that ruptured in to the stomach with hemorrhagic shock and was successfully treated with emergency surgery. CASE PRESENTATION: A 59-year-old man presented to the emergency department with chest pain and syncope. Contrast-enhanced computed tomography showed splenic artery aneurysm with active contrast extravasation. He developed upper gastrointestinal (UGI) bleeding and hypovolemic shock. We diagnosed a splenic artery aneurysm ruptured in to the stomach, performed emergency distal splenopancreatectomy including the aneurysm and partial gastric resection, and could prevent patient death. CONCLUSIONS: This report shows that splenic artery aneurysm can cause UGI bleeding. Thus, clinicians should be alert about this condition when managing patients with UGI bleeding and/or splenic artery aneurysm.

Kinetic Resolution of Tertiary Alcohols by Chiral DMAP Derivatives: Enantioselective Access to 3-Hydroxy-3-substituted 2-Oxindoles.

We developed an efficient acylative kinetic resolution of 3-hydroxy-3-substituted 2-oxindoles by a chiral DMAP derivative having a 1,1'-binaphthyl with two tert-alcohols units. A wide range of 3-hydroxy-3-substituted oxindoles having various functional groups were efficiently resolved (14 examples, up to s = 60) in the presence of 1 mol % of catalyst within 3-9 h. Multigram-scale reactions (10 g) also proceeded with a high s-factor (s = 43) within 5 h.

Acacienone, a terpenoid-like natural product having an unprecedented C20 framework isolated from Acacia mangium leaves.

A novel C20 natural product, acacienone (1), was isolated from the leaves of Acacia mangium collected in Bangladesh. The structure of compound 1 was elucidated by spectral studies and X-ray crystallographic analysis. Acacienone (1) possesses a terpenoid-related tetracyclic framework containing 20 carbons with biogenetically unusual structural features: (i) vicinal C1-branches at the C-3 and C-4 positions in the A ring, and (ii) a cyclopentenone D ring in an androsterone-like assembly, lacking a methyl group at the C-13 position.

Investigation of object-based attention in pigeons (Columba livia) and hill mynas (Gracula religiosa) using a spatial cueing task.

In previous research, pigeons and hill mynas that performed differently on an object permanence task were presumed to attend to objects in different ways (Plowright, Reid, & Kilian, 1998). In the current study, we conducted 4 experiments to investigate if the attention of hill mynas and pigeons is object-based and if there are species differences in their visual-attentional processes. In Experiment 1, pigeons were tested in a spatial cueing task requiring them to respond sequentially to a cue and a target that appeared at 1 of the 4 ends of two rectangles. Both when the response to a fixation stimulus was required before target presentation (Experiment 1A) and when such a response was not required (Experiment 1B), there were no significant differences in reaction times to the targets appearing at cued and noncued rectangles; these results provided no evidence of object-based attention in pigeons. In Experiment 2, for 2 of the 3 hill mynas tested in a procedure similar to that for the pigeons in Experiment 1B, reaction times were shorter to the target appearing on the cued rectangle than to the target appearing on noncued rectangle, suggesting the operation of object-based attention, as in humans. In Experiment 3, we tested naive pigeons by means of the procedure used for hill mynas in Experiment 2. However, again pigeons showed no evidence of object-based attention, suggesting a species difference in attentional processes. The generality of the current results and evolution of the possible species differences were discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).