Connecting the Dots between Septins and the DNA Damage Checkpoint

In budding yeast, septins are involved in the morphogenesis checkpoint and the DNA damage checkpoint, both of which regulate cell-cycle progression. In this issue of Cell, Kremer et al. (2007) link septins to DNA damage in mammalian cells by identifying a new signaling pathway that includes the adaptors SOCS7 and NCK. As NCK controls actin dynamics, this pathway may connect DNA damage responses and cellular morphology in metazoans

Identification of a Xenopus glutamine synthetase gene abundantly expressed in the embryonic nervous system but not in adult brain

AbstractWe used a PCR-based subtraction cloning procedure with concanavalin A-treated and -untreated animal caps from stage 9 Xenopus embryos to search for genes up-regulated during early neural development. One such gene was found to encode a protein homologous to several known glutamine synthetases, and we named it xGS. Molecular hybridization studies revealed that xGS mRNA is maternally transmitted and abundantly expressed in neuroectoderm-derived tissues during the gastrula and neurula stages. The expression of xGS mRNA in the nervous system continues until the larval stages, but declines thereafter and becomes undetectable in adult brain. Considering its metabolic activity and potential neuroprotective effect against the neurotoxic substances such as glutamate and ammonia, the glutamine synthetase may play an important role in the early stages of vertebrate neural development

Spatiotemporal association of DNAJB13 with the annulus during mouse sperm flagellum development

<p>Abstract</p> <p>Background</p> <p>The sperm annulus is a septin-based fibrous ring structure connecting the midpiece and the principal piece of the mammalian sperm flagellum. Although ultrastructural abnormalities and functional importance of the annulus have been addressed in <it>Sept4</it>-null mutant mice and a subset of human patients with asthenospermia syndrome, little is known about how the structure is assembled and positioned to the midpiece-principal piece junction during mammalian sperm flagellum development.</p> <p>Results</p> <p>By performing immunofluorescence and biochemical approaches with antibodies against DNAJB13 and an annulus constituent SEPT4, we report here a spatiotemporal association of DNAJB13 with sperm annulus during mouse sperm flagellum development. DNAJB13 co-localized with SEPT4 to the annulus, and both were first able to be detected in step 9 spermatids. As spermiogenesis proceeded, the annular DNAJB13 immunosignal increased until the annulus reached the midpiece-principal piece junction, and then gradually disappeared from it in late spermiogenesis. In contrast, the SEPT4 immunosignal was relatively unaltered, and still present on annulus of mature spermatozoa. In <it>Sept4</it>-null mouse spermatids lacking the annulus structure, the annulus-like DNAJB13 immunosignal was still able to be detected, albeit weaker, at the neck region of the flagella. In vitro DNAJB13 was co-localized and interacted with SEPT4 directly.</p> <p>Conclusion</p> <p>The direct interaction of DNAJB13 with SEPT4 in vitro and its spatiotemporal association with the annulus during sperm flagellum development, and even its annulus-like appearance in the annulus-deficient spermatids, suggest that DNAJB13 may be involved in assembling the annulus structure and positioning it towards the midpiece-principal piece junction.</p

Preoperative Evaluation of Computed Tomography Perfusion: Its Significance for the Risk Assessment of Cerebrovascular Complications Perioperatively1

Neurological complications occur with an overall frequency of 2.8% perioperatively. Although ultrasound imaging is an excellent modality for the risk assessment of carotid arterial diseases, no comprehensive information can be obtained with respect to the intracranial cerebral blood flow. Recent advent of computed tomography perfusion (CTP) imaging has made it possible to directly measure the cerebral blood flow at any intracranial region of interest. We describe here an efficacy of CT perfusion imaging in the preoperative settings for the risk assessment of neurological complications, especially in cases with carotid arterial stenosis/occlusion

ゲンタマイシン局所投与後モルモット前庭におけるMusashi1の細胞内局在変化

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 栗原 裕基, 東京大学准教授 中冨 浩文, 東京大学講師 清水 潤, 東京大学講師 柳 靖雄, 東京大学講師 二藤 隆春University of Tokyo(東京大学

Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis

Background: The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In the present study, we evaluated a causal relationship between plasma total homocysteine and schizophrenia by conducting a Mendelian randomization analysis. Methods: We used the MTHFR C677T polymorphism as an instrumental variable, which affects the plasma total homocysteine levels. To calculate the risk estimate for the association of this single nucleotide polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case–control studies that comprise a total of 11,042 patients with schizophrenia and 14,557 control subjects. We obtained an estimate for the association of this SNP with the plasma total homocysteine levels from a meta-analysis of genome-wide association studies comprising 44,147 individuals. Results: By combining these two estimates, we demonstrated a significant effect of the plasma total homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39–3.32; p = 5.3 x 10−4) for schizophrenia per 1-SD increase in the natural log-transformed plasma total homocysteine levels. Conclusions: We provided evidence of a causal relationship between the plasma total homocysteine and schizophrenia, and this result will add insight into the pathology and treatment of schizophrenia

Association between BDNF and clinical response in OCD

Aim: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population. Methods: We first performed a case–control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD. Results: We found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05). Conclusion: Our results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population

Left Side Electrode of DBS Caused an Acute Mood Swing

No previous reports have described a case in which deep brain stimulation elicited an acute mood swing from a depressive to manic state simply by switching one side of the bilateral deep brain stimulation electrode on and off. The patient was a 68-year-old woman with a 10-year history of Parkinson’s disease. She underwent bilateral subthalamic deep brain stimulation surgery. After undergoing surgery, the patient exhibited hyperthymia. She was scheduled for admission. On the first day of admission, it was clear that resting tremors in the right limbs had relapsed and her hyperthymia had reverted to depression. It was discovered that the left-side electrode of the deep brain stimulation device was found to be accidentally turned off. As soon as the electrode was turned on, motor impairment improved and her mood switched from depression to mania. The authors speculate that the lateral balance of stimulation plays an important role in mood regulation. The current report provides an intriguing insight into possible mechanisms of mood swing in mood disorders

A gene expression test for depression

Purpose: Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. Patients and methods: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD. Results: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively. Conclusion: Further research to identify MDD-specific markers is needed to improve the performance of this biological test