Heritable effects on caste determination and colony-level sex allocation in termites under field conditions

The ecological success of social insects is attributed to the division of labor, where newly hatched offspring differentiate into either fertile progeny or functionally sterile worker castes. There is growing evidence for the heritable (genetic or epigenetic) effects on caste determination based on laboratory experiments. Here, we indirectly demonstrate that heritable factors have the principal role in caste determination and strongly affect colony-level production of both sexes of fertile dispersers (i.e., alates) in field colonies of the termite Reticulitermes speratus. An egg-fostering experiment suggests that the colony-dependent sex-specific caste fates were almost entirely determined before oviposition. Our investigation of field colonies revealed that such colony-dependent sex-specific caste fates result in the intercolonial variation in the numerical sex ratio of differentiated fertile offspring and, eventually, that of alates. This study contributes to better understanding the mechanisms underlying the division of labor and life-history traits in social insects

統合失調症の早期段階におけるミスマッチ陰性電位とグルタミン酸系アミノ酸の血漿濃度の検討

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 岩坪 威, 東京大学教授 狩野 方伸, 東京大学准教授 島津 明人, 東京大学講師 岩田 淳, 東京大学講師 寺尾 安生University of Tokyo(東京大学

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) serves as an endothelial receptor for advanced glycation end products (AGE)

AbstractAdvanced glycation end products (AGE) are known to serve as ligands for the scavenger receptors such as SR-A, CD36 and SR-BI. In the current study, we examined whether AGE is recognized by lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Cellular binding experiments revealed that AGE-bovine serum albumin (AGE-BSA) showed the specific binding to CHO cells overexpressing bovine LOX-1 (BLOX-1), which was effectively suppressed by an anti-BLOX-1 antibody. Cultured bovine aortic endothelial cells also showed the specific binding for AGE-BSA, which was suppressed by 67% by the anti-BLOX-1 antibody. Thus, LOX-1 is identified as a novel endothelial receptor for AGE

Major Depressive Disorder Complicated with Spinocerebellar Ataxia: Report of 2 Cases

Background: It is known that patients with spinocerebellar ataxia (SCA) tend to exhibit depressive symptoms. But the pathology of depressive symptoms complicated with SCA, including the reaction to the stress resulting from decreased motor function and central dysfunction due to neurodegeneration, is controversial and remains to be elucidated. To our knowledge, there have been hardly any reports on treatment methods of major depressive disorder (MDD) complicated with SCA. Case Reports: We report 2 cases in which selective serotonin reuptake inhibitors (SSRIs) were effective against MDD complicated with SCA. Interestingly, one of the patients developed the symptoms of spinocerebellar degeneration (SCD) during the course of the MDD, and the other patient developed the symptoms of MDD during the course of SCA, but complete remission of the MDD occurred in both cases. In our cases, the depressive symptoms may have been caused mainly by an abnormality of reversible neural transmission including serotonin transmission due to central dysfunction, and there is the unlikely possibility that the depressive symptoms are reactive to the stress due to decreased motor function, because the depressive symptoms decreased with SSRIs. Conclusion: Although cerebellar degeneration is irreversible in SCA patients, our cases suggest that MDD complicated with SCA may be reversible and treatable using antidepressants such as SSRIs with few adverse events. Therefore, it is important for neurologists to detect MDD complicated with SCA early and consult a psychiatrist in order to improve quality of life of SCA patients

Monoclonal antibody to galactosylceramide: discrimination of structural difference in the ceramide moiety

AbstractA mouse monoclonal antibody (mAb) was developed against monohexaosylceramide. This mAb differentially reacted on thin-layer chromatograms with 3 types of galactosylceramide (GalCer) obtained from bovine brain. Structural analysis of the 3 glycolipids revealed that they consisted of the same galactose and sphingosine but of apparently different fatty acids. Among the 3 GalCers, the mAb reacted with two GalCers which contained α-hydroxy fatty acids, but not with GalCer composed of nonhydroxy fatty acids. These findings suggest not only that the mAb discriminated the fatty acid composition in the ceramide moiety of GalCer, but also that the ceramide structure defines the immunological epitope as it is known to do for the carbohydrate moiety of glycosphingolipid

Flash Controls of Proliferation and Senescence through p21

Dysregulation of the cell proliferation has been implicated in the pathophysiology of a number of diseases. Cellular senescence limits proliferation of cancer cells, preventing tumorigenesis and restricting tissue damage. However, the role of cellular senescence in proliferative nephritis has not been determined. The proliferative peak in experimental rat nephritis coincided with a peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded transcription factor) did not promote proliferation of Mesangial cells (MCs) by itself. We identified caspase-8-binding protein FLICE-associated huge protein (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening. Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did not affect p53 expression. Furthermore, overexpression of E12 and E47 induced p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A and p21 expression at the peak of proliferation was followed by significant induction of FLASH in mesangial areas in rat proliferative glomerulonephritis. Moreover, we revealed that FLASH negatively regulates cellular senescence via the interaction with E12. We also demonstrated that FLASH is involved in the TNF-α-induced p21 expressions. These results suggest that the functional interaction of E2A and FLASH play an important role in cell proliferation and cellular senescence via regulation of p21 expression in experimental glomerulonephritis

Periprosthetic Bone Mineral Density Changes after Cementless Total Knee Arthroplasty

Bony atrophy around the components following total knee arthroplasty (TKA) is often observed by radiography. To investigate the underlying cause of this incidence, we sought to quantitatively evaluate postoperative bone changes around the total knee components using dual-energy X-ray absorptiometry (DXA) over time. A retrospective study was conducted to compare bone mineral density (BMD) around the components in 22 patients pre-operatively and at 1, 3, 6, 12, and 24 months after cementless TKA for the treatment of osteoarthritis. In the coronal view, the medial tibia showed that a significant decrease in BMD at 12 months compared with 1 month after surgery (P<0.05), while the sagittal view showed that a significant decrease in BMD only at the anterior femoral condyle at 24 months compared with 1 month postoperatively (P<0.05). TKA improved the leg alignment and load-bearing axis in all patients, but we found that BMD tended to decrease on the medial side of the tibia and the anterior femoral condyle area over time following surgery. Our results suggest that recreating proper valgus alignment of the knee joint provides physiological balancing and condition. A larger prospective study is warranted

BMP4 in Diabetic Nephropathy

Podocyte injury and loss have been indicated as constituting the crucial pathogenesis of glomerular injury ; however, it remains necessary to elucidate the detailed molecular mechanisms and cell-to-cell response because multiple factors may cause podocyte injury. In the glomerulus, three kinds of cells (endothelial, mesangial, and parietal epithelial) react to podocyte injury. Endothelial and mesangial cells are connected with podocyte cells across the glomerular basement membrane. However, the detailed mechanisms regarding the interaction of the mesangium and podocyte injury are unclear. Diabetic nephropathy is characterized by mesangial matrix expansion caused by an excessive deposition of extracellular matrix proteins in the mesangial area, which can be observed through the increased expression of type IV collagen. We have shown that bone morphogenetic protein 4 (BMP4) signaling leads to the glomerular changes characteristic of this disorder. To analyze the effect of BMP4 was investigated in vitro and in vivo using streptozotocin (STZ)-induced and Bmp4 heterozygous knockout (Bmp4+/-) diabetic mice or podocyte-specific Bmp4 knockout mice, and Bmp4-induced or podocyte-specific transgenic mice. BMP4 positive area and mesangial area fraction showed positively correlation. Furthermore, mesangial area fraction was significantly and negatively correlated with,WT1-positive cell number, and nephrin-positive area. We also demonstrated that the induction of podocyte apoptosis by BMP4 may be mediated by p38 activation and that of caspase 3 through cleavage. In mesangial cells, BMP4 stimulation also induced phosphorylation of p38 and Smad1 and increased cleaved caspase 3, with similar significant inhibition of Smad1 activation and decreased cleaved caspase 3 mediated by dorsomorphin. These data suggest that the BMP4 signaling pathway plays important roles for the development of both podocyte injury and mesangial expansion in diabetic nephropathy

Role of Elf3 in diabetic nephropathy

Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression of RII and activation of Smad3 were induced by AGE exposure (P<0.05). Reduction of the activation of RII-Smad3 signaling ameliorated podocyte injuries in Smad3-knockout diabetic mice. The bone morphogenetic protein 4 (BMP4) significantly regulated activation of RII-Smad3 signalings (P<0.05). Moreover, the epithelium-specific transcription factor, Elf3was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3 signaling, leading to a decrease in WT1 expression, were observed in podocytes in diabetic human kidneys. Moreover, AGE treatment induced the secretion of Elf3-containing exosomes from cultured podocytes, which was dependent on the activation of the TGF-β-Smad3 signaling pathway. In addition, exosomal Elf3 protein in urine could be measured only in urinary exosomes from patients with DN. The appearance of urinary exosomal Elf3 protein in patients with DN suggested the existence of irreversible injuries in podocytes. The rate of decline in the estimated Glomerular Filtration Rate (eGFR) after measurement of urinary exosomal Elf3 protein levels in patients with DN (R2 = 0.7259) might be useful as an early non-invasive marker for podocyte injuries in DN