Preferential binding of a kinesin-1 motor to GTP-tubulin-rich microtubules underlies polarized vesicle transport.

Polarized transport in neurons is fundamental for the formation of neuronal circuitry. A motor domain-containing truncated KIF5 (a kinesin-1) recognizes axonal microtubules, which are enriched in EB1 binding sites, and selectively accumulates at the tips of axons. However, it remains unknown what cue KIF5 recognizes to result in this selective accumulation.

Establishment of in vitro P-glycoprotein inhibition assay and its exclusion criteria to assess the risk of drug-drug interaction at the drug discovery stage.

The decision tree to determine whether the P-glycoprotein (P-gp)/multidrug resistance protein 1 (MDR1)-mediated drug-drug interaction (DDI) study is recommended has been proposed by the International Transporter Consortium. We, therefore, designed an in vitro P-gp inhibition assay and determined the appropriate risk criteria for P-gp-mediated DDI at the drug discovery stage. Effects of P-gp inhibitors on digoxin transport across a monolayer of MDR1-expressing cells were examined.

Intermediate-conductance Ca2+-activated K+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia.

Recently, a new experimental stromal hyperplasia animal model corresponding to clinical benign prostatic hyperplasia (BPH) was established. The main objective of this study was to elucidate the roles of the intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) in the implanted urogenital sinus (UGS) of stromal hyperplasia BPH model rats.

Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels.

An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers.

Temporal integration of deviant sound in automatic detection reflected by mismatch negativity.

Mismatch negativity (MMN) is an event-related potential that is elicited by deviant sounds that are presented along with frequent sounds in the absence of attention. Auditory MMN is generated by the comparison process between sensory memory trace of a frequent auditory event and a deviant event. It is well known that frequent sounds are encoded in memory trace and processed as a single unit within 160-170 ms.

Comparative community outreach to increase cervical cancer screening in the Mississippi Delta.

Objective: The aim of the study was to increase participation in cervical cancer screening of under-screened women living in the Mississippi Delta, a U.S. population at high risk for cervical cancer.

Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry.

Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia.

Event-related potentials in patients with adult attention-deficit/hyperactivity disorder versus schizophrenia.

Event-related potentials (ERPs) such as Nd, N2b, and P300 in an attentional task and an auditory oddball task were compared among 54 adult AD/HD patients, 43 schizophrenic patients (SZ), and 40 healthy age-matched volunteers (HC). It is known that Nd, N2b, and P300 reflect selective attention, voluntary attention, and cognitive context updating respectively. The peak amplitude of P300 was significantly lower in the adult AD/HD and SZ groups than in the HC group.

Altered DARPP-32 expression in the superior temporal gyrus in schizophrenia.

Many neuroimaging studies have revealed structural abnormalities in the superior temporal gyrus (STG) in schizophrenia (Kasai et al., 2003a, 2003b; Sun et al., 2009).

Neural bases of a specific strategy for visuospatial processing in rugby players.

Introduction: Rugby is one of the most tactically complex sports. Rugby coaching theory suggests that rugby players need to possess various cognitive abilities. A previous study claimed that rugby players have high visuospatial awareness, which is induced by a strategy described as taking a "bird's eye view.

Involvement of dominant-negative spliced variants of the intermediate conductance Ca2+-activated K+ channel, K(Ca)3.1, in immune function of lymphoid cells.

The intermediate conductance Ca(2+)-activated K(+) channel (IK(Ca) channel) encoded by K(Ca)3.1 is responsible for the control of proliferation and differentiation in various types of cells. We identified novel spliced variants of K(Ca)3.

A validation study of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) for patients with chronic low back pain (verification of reliability, validity, and reproducibility).

Introduction: We developed the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) (doctor and patient versions). The present study aimed to proactively verify the factorial validity, internal consistency, criterion-related validity and reproducibility of the BS-POP with regard to chronic low back pain patients.

Methods: Subjects comprised 193 chronic low back pain patients.

Effect of Storage Temperature on Soil Nematode Community Structures as Revealed by PCR-DGGE.

The optimal duration and conditions for storage of soils collected for nematode community analyses are unknown. To study this issue, three types of soils with different geographical origins from the subarctic to cool-temperate Japan were kept at three temperature levels (5, 10, and 20(°)C) for up to 8 wk following collection. During the storage period, nematode population density was measured, and community structure was assessed by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE).

Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease.

The kinesin, dynein, and myosin superfamily molecular motors have fundamental roles in neuronal function, plasticity, morphogenesis, and survival by transporting cargos such as synaptic vesicle precursors, neurotransmitter and neurotrophic factor receptors, and mRNAs within axons, dendrites, and synapses. Recent studies have begun to clarify the mechanisms of cargo selection and directional transport in subcellular compartments. Furthermore, molecular genetics has revealed unexpected roles for molecular motors in brain wiring, neuronal survival, neuronal plasticity, higher brain function, and control of central nervous system and peripheral nervous system development.

Paroxysmal EEG abnormalities and epilepsy in pervasive developmental disorders: follow-up study until adolescence and beyond.

This study examined paroxysmal abnormalities and epilepsy in EEG for individuals with pervasive developmental disorders (PDD) in two parts: first with a large number of subjects (n=1624); and second with extracted subjects followed from 5 years into adolescence and beyond (n=92). Many paroxysms in PDD patients in their childhood tended to appear at various sites and the same held for paroxysms at the time of epilepsy onset. However, in adolescence and beyond, paroxysms in the frontal region prevailed as those appearing at sites other than the frontal region tended to disappear.

Hurdles in the drug discovery of cathepsin K inhibitors.

There were many hurdles in the drug discovery of cathepsin K inhibitors such as species differences not only in bone metabolism but also in amino acid sequences in the critical site of the target enzyme, discrepancies between PK/PD due to unique tissue distribution of the inhibitor affecting both efficacy and side effects originated from a characteristic intracellular or tissue distribution of some classes of compounds. The value of this new therapeutic approach over the launched indirect competitors should be further clarified from the efficacy and side effect point of view. The cathepsin K inhibitor drug discovery was initiated based on a strong and osteoclast-specific expression of this enzyme.

Measuring serum melatonin in epidemiologic studies.

Background: Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies.

Methods: To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin RIA, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups.

Results: Reproducibility was high for the standard 1.

Development of a simplified Short-Term Memory recall Test (STMT) and its clinical evaluation.

Background And Aims: The early detection and prevention of dementia is attracting attention. We therefore developed an easily performed protocol to identify patients with memory impairment which may progress to dementia, and evaluated its validity.

Methods: We focused on short-term memory impairment alone, and named the test, consisting of 3 tasks, the simplified Short-Term Memory recall Test (STMT; with a maximum score of 8).

Androgen receptor CAG repeat length and risk of biliary tract cancer and stones.

Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens.

Ovalbumin-induced plasma interleukin-4 levels are reduced in ceramide kinase-deficient DO11.10 RAG1-/- mice.

Ceramide kinase (CERK) produces the bioactive lipid ceramide-1-phosphate (C1P) and is a key regulator of ceramide and dihydroceramide levels. It is likely that CERK and C1P play a role in inflammatory processes but the cells involved and the mechanisms used remain to be clarified. In particular, the impact of CERK on T-cell biology has not been studied so far.

Tumor necrosis factor-alpha regulates transforming growth factor-beta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction.

Aberrant epithelial-mesenchymal transition (EMT) is involved in development of fibrotic disorders and cancer invasion. Alterations of cell-extracellular matrix interaction also contribute to those pathological conditions. However, the functional interplay between EMT and cell-extracellular matrix interactions remains poorly understood.

KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in enteric neuronal development.

The kinesin superfamily proteins (KIFs) are motor proteins that transport organelles and protein complexes in a microtubule- and ATP-dependent manner. We identified KIF26A as a new member of the murine KIFs. KIF26A is a rather atypical member as it lacks ATPase activity.

Auricular Acupunctures are Effective for the Prevention of Postoperative Agitation in Old Patients.

Postoperative cognitive problems and delirium are not uncommon in the elderly. We reported four cases in which auricular acupunctures on the 'Shenmen' and 'Point Zero' points successfully managed postoperative problematic behaviors of the three patients with dementia and the one patient postoperatively demonstrating an agitated behavior.

The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems.

To elucidate the cellular distribution of osteopontin (OPN) in normal human tissues, we undertook immunohistochemistry using two site-specific OPN antibodies. The 10A16 monoclonal antibody was raised against the amino acid sequence just downstream of the thrombin cleavage site, while the O-17 polyclonal antibody was raised against the N-terminal peptide. Each antibody has been confirmed previously to react with both whole OPN and its relevant fragments.