The involvement of oxysterol-binding protein related protein (ORP) 6 in the counter-transport of phosphatidylinositol-4-phosphate (PI4P) and phosphatidylserine (PS) in neurons.

Oxysterol-binding protein (OSBP)-related protein (ORP) 6, a member of subfamily III in the ORP family, localizes to membrane contact sites between the endoplasmic reticulum (ER) and other organelles and functions in non-vesicular exchange of lipids including phosphatidylinositol-4-phosphate (PI4P) in neurons. In this study, we searched for the lipid counter-transported in exchange for PI4P by using molecular cell biology techniques. Deconvolution microscopy revealed that knockdown of ORP6 partially shifted localization of a phosphatidylserine (PS) marker but not filipin in primary cultured cerebellar neurons.

Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3' Untranslated Region in Central Nervous System Neurons.

Fragile X syndrome (FXS) is an inherited intellectual disability caused by a deficiency in Fragile X mental retardation 1 () gene expression. Recent studies have proposed the importance of cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in FXS pathology; however, the molecular interaction between mRNA and CPEB1 has not been fully investigated. Here, we revealed that CPEB1 co-localized and interacted with mRNA in hippocampal and cerebellar neurons and culture cells.

Cpeb1 expression is post-transcriptionally regulated by AUF1, CPEB1, and microRNAs.

Cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates the translation of numerous mRNAs. We previously showed that AU-rich binding factor 1 (AUF1) regulates Cpeb1 expression through the 3' untranslated region (3'UTR). To investigate the molecular basis of the regulatory potential of the Cpeb1 3'UTR, here we performed reporter analyses that examined expression levels of Gfp reporter mRNA containing the Cpeb1 3'UTR.

Effect of long-term confinement on metabolic and physiological parameters in mice.

Long-term and mild confinement or isolation in an enclosed environment can occur in situations such as disasters, specific political, economic or social events, nuclear shelters, seabed exploration, polar expeditions, and space travel. To investigate the effects of stress caused by long-term confinement in an enclosed environment in mammals, we divided 8-week-old C57BL/6J mice into four groups that were housed in a closed environment with a narrow metabolic cage (stress group), normal metabolic cage (control group), conventional cage (conventional group) or conventional cage with wire mesh floor (wire mesh group). The phenotypes of the mice were examined for four weeks, followed by behavioral tests.

AUF1, an mRNA decay factor, has a discordant role in Cpeb1 expression.

Cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates polyadenylation and subsequent translation of CPE-containing mRNAs involved in various physiological and pathological phenomena. Although the significance of CPEB1-mediated translational regulation has recently been reported, the detailed regulatory mechanism of Cpeb1 expression remains unclear. To elucidate the post-transcriptional regulatory mechanisms of Cpeb1 expression, we constructed reporter plasmids containing various deletions or mutations in the Cpeb1 mRNA 3' untranslated region (3'UTR).

Surgical anatomy of the pelvis for total pelvic exenteration with distal sacrectomy: a cadaveric study.

Purpose: Intraoperative bleeding from the pelvic venous structures is one of the most serious complications of total pelvic exenteration with distal sacrectomy. The purpose of this study was to investigate the topographic anatomy of these veins and the potential source of the bleeding in cadaver dissections.

Methods: We dissected seven cadavers, focusing on the veins in the surgical resection line for total pelvic exenteration with distal sacrectomy.

Couinaud Type A communicating accessory bile duct: report of a case.

Background: Communicating accessory bile ducts are defined as ducts that communicate between major biliary channels but do not drain individual segments of the liver. The Couinaud Type A communicating accessory bile duct is a rare anomaly where an aberrant duct connects the right main hepatic duct to the common hepatic duct without segmental drainage. There are very few reports of this anomaly in the literature to date.

Oxysterol-binding protein-related protein (ORP) 6 localizes to the ER and ER-plasma membrane contact sites and is involved in the turnover of PI4P in cerebellar granule neurons.

Oxysterol-binding protein (OSBP)-related proteins (ORPs) are conserved lipid binding proteins found in organisms ranging from yeast to mammals. Recent findings have indicated that these proteins mainly localize to contact sites of 2 different membranous organelles. ORP6, a member of the ORP subfamily III, is one of the least studied ORPs.

Optical clearing of the pancreas for visualization of mature β-cells and vessels in mice.

Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner.

Reappraisal of the lateral rectal ligament: an anatomical study of total mesorectal excision with autonomic nerve preservation.

Purpose: The term "lateral rectal ligament" in surgery for rectal cancer has caused confusion regarding its true existence and contents. In previous studies, investigators claimed the existence of the ligament and described its topographical features as neurovascular structures and their surrounding connective tissues located at the anterolateral aspect of the distal rectum or the posterolateral aspect of the middle rectum. The purpose of this study is to evaluate the structure of the so-called "lateral rectal ligament" in cadaver dissections.

Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer.

Pathological complete response (pCR) is considered to be a useful prognostic marker for neoadjuvant chemotherapy to improve the survival rate of patients with operable breast cancer. In the present study, we identified differentially expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab. Expression profiles were examined by miRNA microarrays using total RNA extracted from formalin-fixed, paraffin-embedded tissues from pretreatment biopsy specimens.

The Anticonvulsant Zonisamide Inhibits Hydroxyl Radical Generated from Methylguanidine.

Methylguanidine (MG) is a known nephrotoxin and neurotoxin, and an intracisternal injection of MG can induce convulsions in experimental animals. In this in vitro study, we examined the inhibitory effects of the antiepileptic agent zonisamide (ZNS) on hydroxyl radicals (•OH) generated from MG by using an electron spin resonance (ESR) technique. ZNS scavenged •OH generated from MG in a dose-dependent manner through direct scavenging during the auto-oxidation of MG.

Mechanism of the Dendritic Translation and Localization of Brain-derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor critical for synaptic plasticity, neuronal development and neurite extension. BDNF mRNA is transported to dendrites and axons, where it is expressed locally. We previously reported that dendritic targeting elements in the BDNF 3' UTR are necessary for dendritic transport and interact with cytoplasmic polyadenylation element binding protein 1.

Demethylation of the MafB promoter in a compromised β-cell model.

Recent studies suggest that dedifferentiation of pancreatic β-cells is involved in compromised β-cell function in diabetes mellitus. We have previously shown that the promoter activity of MafB, which is expressed in α-cells of adult islets and immature β-cells in embryonic pancreas but not in mature β-cells in mice, is increased in compromised β-cells of diabetic model mice. Here, we investigated a rat β-cell line of INS1 cells with late-passage numbers, which showed extremely low expression of MafA and insulin, as an in vitro model of compromised β-cells.

[Results of a questionnaire on efforts to increase research-oriented doctors].

We surveyed medical and dental schools to promote the exchange of information about university efforts to increase the number of research-oriented doctors. Periods in which students rotate through laboratories to conduct research were reported by more than two thirds of universities. Many comments asserted that these efforts are effective.

Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L.

AMPA receptor (AMPA-R) complexes consist of channel-forming subunits, GluA1-4, and auxiliary proteins, including TARPs, CNIHs, synDIG1, and CKAMP44, which can modulate AMPA-R function in specific ways. The combinatorial effects of four GluA subunits binding to various auxiliary subunits amplify the functional diversity of AMPA-Rs. The significance and magnitude of molecular diversity, however, remain elusive.

Distribution of cytoskeletal components in endothelial cells in the Guinea pig renal artery.

The cytoskeletal components of endothelial cells in the renal artery were examined by analysis of en face preparations under confocal laser scanning microscopy. Renal arterial endothelial cells were shown to be elongated along the direction of blood flow, while stress fibers ran perpendicular to the flow in the basal portion. Focal adhesions were observed along the stress fibers in dot-like configurations.

Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches.

Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive.

[Final report of the working group for the future planning of the Japanese Association of Anatomists].

The working group for the future planning of the Japanese Association of Anatomists (JAA) has been working to address the issues that were consulted from the president of JAA since October 2009. After making the interim report in March 2010, a public hearing for general members of the JAA was held and a final report was submitted to the President in January 2011. The report contains the analysis of the current situation, the directions in which we should proceed, and recommendations of concrete actions that JAA should take for each issue.

[Effect of repeated intravitreal bevacizumab injections for secondary macular edema of branch retinal vein occlusion].

Purpose: To evaluate the effects of intravitreal bevacizumab (IVB) injections for secondary macular edema of branch retinal vein occlusion (BRVO).

Subjects And Methods: We treated 91 patients (91 eyes) with IVB injections (1.25 mg/0.

Rho-associated kinase-dependent contraction of stress fibres and the organization of focal adhesions.

Stress fibres and associated focal adhesions in cells constitute a contractile apparatus that regulates cell motility and contraction. Rho-kinase, an effector molecule of small GTPases, regulates non-muscle cell motility and contractility. Rho-kinase mediates the contraction of stress fibres in a Ca(2+)-independent manner, and is responsible for slower and more finely tuned contraction of stress fibres than that regulated by myosin light chain kinase activity in living cells.

Kinesin superfamily motor proteins and intracellular transport.

Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified.

Inhibitory effect of fermented papaya preparation on hydroxyl radical generation from methylguanidine.

We have previously shown that extremely high level of guanidino compounds such as methylguanidine (MG), known as a neurotoxin and also a nephrotoxin, generate reactive oxygen species (ROS) using an electron spin resonance (ESR) technique with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In this in vitro study, the inhibitory effect of fermented papaya preparation (SAIDO-PS501:PS-501) on hydroxyl radical (.OH) generation from MG was examined using an ESR spectrometry, and it was found that PS-501 suppressed .

Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake.

Glucose metabolism is essential for normal brain function and plays a vital role in synaptic transmission. Recent evidence suggests that ATP synthesized locally by glycolysis, particularly via glyceraldehyde 3-phosphate dehydrogenase/3-phosphoglycerate kinase, is critical for synaptic transmission. We present evidence that ATP generated by synaptic vesicle-associated pyruvate kinase is harnessed to transport glutamate into synaptic vesicles.

Inhibitory effect of antioxidants on hydroxyl radical generation from methylguanidine: an ESR study.

Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (*OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K(1) (alpha-tocopheryl-L-ascorbate-2-O-phosphate diester), Trolox (water-soluble vitamin E analogue), and glutathione (GSH) on *OH generation from MG using an electron spin resonance (ESR) spectrometry with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO).