Expression of glutathione S-transferase P-form in primary cultured rat liver parenchymal cells by coplanar polychlorinated biphenyl congeners is suppressed by protein kinase inhibitors and dexamethasone

AbstractGlutathione S-transferase P-form (GST-P, EC 2.5.1.18) mRNA was expressed by epidermal growth factor as well as by 3,4,5,3',4'-penta-chlorinated biphenyl (PenCB) in primary cultured rat liver parenchymal cells. The expression of GST-P was suppressed by inhibitors of protein kinase C and dexamethasone, an antagonist of AP-1 transcription factor activity, whereas expression of cytochrome P4501A2 by PenCB was not affected by these reagents. The AP-1 related transcription factor may be essential for the expression of GST-P by PenCB as also may be a protein kinase C type enzyme

A Perturbative Study of a General Class of Lattice Dirac Operators

A perturbative study of a general class of lattice Dirac operators is reported, which is based on an algebraic realization of the Ginsparg-Wilson relation in the form $\gamma_{5}(\gamma_{5}D)+(\gamma_{5}D)\gamma_{5} = 2a^{2k+1}(\gamma_{5}D)^{2k+2}$ where $k$ stands for a non-negative integer. The choice $k=0$ corresponds to the commonly discussed Ginsparg-Wilson relation and thus to the overlap operator. We study one-loop fermion contributions to the self-energy of the gauge field, which are related to the fermion contributions to the one-loop $\beta$ function and to the Weyl anomaly. We first explicitly demonstrate that the Ward identity is satisfied by the self-energy tensor. By performing careful analyses, we then obtain the correct self-energy tensor free of infra-red divergences, as a general consideration of the Weyl anomaly indicates. This demonstrates that our general operators give correct chiral and Weyl anomalies. In general, however, the Wilsonian effective action, which is supposed to be free of infra-red complications, is expected to be essential in the analyses of our general class of Dirac operators for dynamical gauge field.Comment: 30 pages. Some of the misprints were corrected. Phys. Rev. D (in press

Domain wall fermion and CP symmetry breaking

We examine the CP properties of chiral gauge theory defined by a formulation of the domain wall fermion, where the light field variables $q$ and $\bar q$ together with Pauli-Villars fields $Q$ and $\bar Q$ are utilized. It is shown that this domain wall representation in the infinite flavor limit $N=\infty$ is valid only in the topologically trivial sector, and that the conflict among lattice chiral symmetry, strict locality and CP symmetry still persists for finite lattice spacing $a$. The CP transformation generally sends one representation of lattice chiral gauge theory into another representation of lattice chiral gauge theory, resulting in the inevitable change of propagators. A modified form of lattice CP transformation motivated by the domain wall fermion, which keeps the chiral action in terms of the Ginsparg-Wilson fermion invariant, is analyzed in detail; this provides an alternative way to understand the breaking of CP symmetry at least in the topologically trivial sector. We note that the conflict with CP symmetry could be regarded as a topological obstruction. We also discuss the issues related to the definition of Majorana fermions in connection with the supersymmetric Wess-Zumino model on the lattice.Comment: 33 pages. Note added and a new reference were added. Phys. Rev.D (in press

Complex sequencing rules of birdsong can be explained by simple hidden Markov processes

Complex sequencing rules observed in birdsongs provide an opportunity to investigate the neural mechanism for generating complex sequential behaviors. To relate the findings from studying birdsongs to other sequential behaviors, it is crucial to characterize the statistical properties of the sequencing rules in birdsongs. However, the properties of the sequencing rules in birdsongs have not yet been fully addressed. In this study, we investigate the statistical propertiesof the complex birdsong of the Bengalese finch (Lonchura striata var. domestica). Based on manual-annotated syllable sequences, we first show that there are significant higher-order context dependencies in Bengalese finch songs, that is, which syllable appears next depends on more than one previous syllable. This property is shared with other complex sequential behaviors. We then analyze acoustic features of the song and show that higher-order context dependencies can be explained using first-order hidden state transition dynamics with redundant hidden states. This model corresponds to hidden Markov models (HMMs), well known statistical models with a large range of application for time series modeling. The song annotation with these models with first-order hidden state dynamics agreed well with manual annotation, the score was comparable to that of a second-order HMM, and surpassed the zeroth-order model (the Gaussian mixture model (GMM)), which does not use context information. Our results imply that the hierarchical representation with hidden state dynamics may underlie the neural implementation for generating complex sequences with higher-order dependencies

Magnetohydrodynamic stability at the edge region in H-mode plasmas with long edge-localized-mode-free phases in the large helical device

Clear suppression of magnetic fluctuations associated with resistive interchange modes (RICs) is observed during long edge-localized-mode (ELM)-free phases of the H-mode plasma in an outward-shifted configuration of the Large Helical Decice, in which a steep pressure gradient is generated at the plasma edge in the magnetic hill. The ELM-free H-phase is interrupted by large amplitude ELMs which are thought to be induced through nonlinear evolution of the RICs having m  =  1/n  =  1 dominant component (m: poloidal mode number, n: toroidal one). The m  =  1/n  =  1 RIC amplitude is enhanced about 10 times compared with the H-phase level during each ELM. In most of the H-mode shots, the final ELM-free phase returns to L-phase by a large amplitude ELM. In the L-phase, the RIC amplitude is enhanced by a factor of ~3 compared with that in the H-phase, although the edge pressure gradient is reduced considerably. Linear resistive magnetohydrodynamic stability analysis is attempted using experimentally obtained equilibrium profiles. From the numerical analysis, the distance between the location of the steepest pressure gradient and the main mode resonance surface, i.e. the rotational transform ι  =  1, is found to be important for a large growth of the m  =  1/n  =  1 RIC in the H-phase

Benign giant mediastinal schwannoma presenting as cardiac tamponade in a woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Mediastinal schwannomas are typically benign and asymptomatic, and generally present no immediate risks. We encountered a rare case of a giant benign posterior mediastinal schwannoma, complicated by life-threatening cardiac tamponade.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Japanese woman, who presented with cardiogenic shock. Computed tomography of the chest revealed a posterior mediastinal mass 150 cm in diameter, with pericardial effusion. The cardiac tamponade was treated with prompt pericardial fluid drainage. A biopsy was taken from the mass, and after histological examination, it was diagnosed as a benign schwannoma, a well-encapsulated non-infiltrating tumor, originating from the intrathoracic vagus nerve. It was successfully excised, restoring normal cardiac function.</p> <p>Conclusion</p> <p>Our case suggests that giant mediastinal schwannomas, although generally benign and asymptomatic, should be excised upon discovery to prevent the development of life-threatening cardiopulmonary complications.</p

Dynamic Expression of Cadherins Regulates Vocal Development in a Songbird

BACKGROUND: Since, similarly to humans, songbirds learn their vocalization through imitation during their juvenile stage, they have often been used as model animals to study the mechanisms of human verbal learning. Numerous anatomical and physiological studies have suggested that songbirds have a neural network called 'song system' specialized for vocal learning and production in their brain. However, it still remains unknown what molecular mechanisms regulate their vocal development. It has been suggested that type-II cadherins are involved in synapse formation and function. Previously, we found that type-II cadherin expressions are switched in the robust nucleus of arcopallium from cadherin-7-positive to cadherin-6B-positive during the phase from sensory to sensorimotor learning stage in a songbird, the Bengalese finch. Furthermore, in vitro analysis using cultured rat hippocampal neurons revealed that cadherin-6B enhanced and cadherin-7 suppressed the frequency of miniature excitatory postsynaptic currents via regulating dendritic spine morphology. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of cadherins in vocal development, we performed an in vivo behavioral analysis of cadherin function with lentiviral vectors. Overexpression of cadherin-7 in the juvenile and the adult stages resulted in severe defects in vocal production. In both cases, harmonic sounds typically seen in the adult Bengalese finch songs were particularly affected. CONCLUSIONS/SIGNIFICANCE: Our results suggest that cadherins control vocal production, particularly harmonic sounds, probably by modulating neuronal morphology of the RA nucleus. It appears that the switching of cadherin expressions from sensory to sensorimotor learning stage enhances vocal production ability to make various types of vocalization that is essential for sensorimotor learning in a trial and error manner

Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese

Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle.To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4)).With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population

The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin

Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca2+; (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca2+ homeostasis leading to membrane dysfunction and enhancement of virus release

Association between an 8q24 locus and the risk of colorectal cancer in Japanese

<p>Abstract</p> <p>Background</p> <p>A genome-wide association study (GWAS), which assessed multiple ethnicities, reported an association between single nucleotide polymorphisms in the 8q24 region and colorectal cancer risk. Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited.</p> <p>Methods</p> <p>We conducted a case-control study in 481 patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer controls. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models that considered potential confounders.</p> <p>Results</p> <p>We found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after adjustment for confounders (OR = 1.25). No statistically significant interaction with potential confounding factors was observed.</p> <p>Conclusion</p> <p>The polymorphism rs6983267 showed a significant association with CRC in a Japanese population. Further investigation of the biological mechanism of this association is warranted.</p