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Enterovirus 68 (EV68) is a rare enterovirus associated with respiratory illness that, unlike other enteroviruses, has been identified only from respiratory specimens. We identified EV68 from respiratory specimens of children hospitalized with a diagnosis of severe pneumonia in Leyte, Republic of the Philippines. Twenty-one samples showed high similarity with EV68 by sequencing of 5' nontranslated region; 17 of these samples were confirmed as EV68 by sequencing of viral protein 1 capsid coding region. Most previously reported EV68 cases had been identified as sporadic cases. All 21 patients we identified had severe illness, and 2 died, possibly the first reported fatal cases associated with EV68 infection. Our study suggests that EV68 may be a possible causative agent of severe respiratory illnesses. [ABSTRACT FROM AUTHOR]

Abstract: In recent years, Boolean Gröbner bases have attracted the attention of many researchers, mainly in connection with cryptography. Several sophisticated methods have been developed for the computation of Boolean Gröbner bases. However, most of them only deal with Boolean polynomial rings over the simplest coefficient Boolean ring . Boolean Gröbner bases for arbitrary coefficient Boolean rings were first introduced by two of the authors almost two decades ago. While the work is not well-known among computer algebra researchers, recent active work on Boolean Gröbner bases inspired us to return to their development. In this paper, we introduce our work on Boolean Gröbner bases with arbitrary coefficient Boolean rings. [Copyright &y& Elsevier]

Abstract: Two peculiar convection patterns–re-oscillation and stable non-centrosymmetric convection–are observed when two-dimensional double-diffusive convection in a porous enclosure (aspect ratio=1.5) is analysed numerically. The top and bottom walls of the enclosure are insulated; constant and opposing heat and mass fluxes are prescribed on the vertical walls. Re-oscillation occurs when the convection pattern changes from centrosymmetric to non-centrosymmetric. When the buoyancy ratio, which generates re-oscillation convection, is marginally lower, the convection pattern changes to stable non-centrosymmetric. These two convection patterns can be observed only for limited values of the Rayleigh number, Lewis number, and buoyancy ratio. [Copyright &y& Elsevier]

Abstract: The removal of blue-green algae by dispersed gas flotation was conducted. Methylated ovalbumin (MeOA) was used as frother and flocculant, which is a biodegradable substance. The continuous flotation experiments were conducted at different feed mass flow rate of the blue-green algae cells and MeOA. The operating variables were the mass flow rate of blue-green algae cell and MeOA, the initial concentration of the cells and MeOA, and superficial gas velocity. The results showed that the mass flow rate of MeOA was the most dominant variable affected by the removal efficiency and that the removal efficiency achieved ca. 0.85 when a ratio of the mass flow rate of MeOA and that of the cells was over 0.3. A proposed flotation model considering the adsorptions of MeOA to the cells, MeOA to bubble surface and the cells bearing with MeOA to bubble surface was applied to explain the experimental removal efficiency. The experimental and the calculated removal efficiency were within error 19%, indicating that the proposed model was valid fundamentally. [Copyright &y& Elsevier]

The article presents a study which investigates the endocrine disruptive effects of isolated 3-methyl-4-nitrophenol (PNMC) in diesel exhaust particles (DEP) through Hershberger assay in immature rats. It reveals that PNMC has increased the weights of the rats' seminal vesicles and their Cowper's glands, and the concentration of plasma testosterone. In addition, it has reduced the weight of the livers as well as the plasma follicle-stimulating hormone and luteinizing hormone of the subjects.

Abstract: Keratinocyte-specific Pten-null mice revealed distinct phenotypes, including epidermal and sebaceous gland hyperplasia. To determine the candidate genes that contribute to their phenotypes, we analyzed a comprehensive gene expression of Pten-null keratinocytes using microarray technology. Consequently, it was demonstrated that the most induced gene was adipocyte-specific fatty acid-binding protein (FABP4). Collectively, it is conceivable that the FABP4 pathway mediates the sebaceous gland hyperplasia in keratinocyte-specific Pten-null mice. [Copyright &y& Elsevier]

Better preparedness for an influenza pandemic mitigates its impact. Many countries have started developing and implementing national influenza pandemic preparedness plans. However, the level of preparedness varies among countries. Developing countries encounter unique and difficult issues and challenges in preparing for a pandemic. Deaths attributable to an influenza pandemic could be substantially higher in developing countries than in industrialized countries. Pharmaceutical interventions such as vaccines and antiviral agents are less likely to be available in developing countries. The public health and clinical infrastructure of developing countries are often inadequate to deal with a widespread health crisis such as an influenza pandemic. Such an event will inevitably have a global effect. Therefore, improving pandemic preparedness in every country, particularly developing ones, is urgently needed. [ABSTRACT FROM AUTHOR]

PTEN is a tumor suppressor gene but whether cancer can develop in all PTEN-deficient cells is not known. In T cell-specific PTEN-deficient (tPTEN-/-) mice, which suffer from mature T cell lymphomas, we found that premalignancy, as defined by elevated AKT and senescence pathways, starts in immature T cell precursors and surprisingly not in mature T cells. Premalignancy only starts in 6-week-old mice and becomes much stronger in 9-week-old mice although PTEN is lost since birth. tPTEN-/- immature T cells do not become tumors, and senescence has no role in this model because these cells exist in a novel cell cycle state, expressing proliferating proteins but not proliferating to any significant degree. Instead, the levels of p27kip1, which is lower in tPTEN-/- immature T cells and almost nonexistent in tPTEN-/- mature T cells, correlate with the proliferation capability of these cells. Interestingly, transient reduction of these cancer precursor cells in adult tPTEN-/- mice within a crucial time window significantly delayed lymphomas and mouse lethality. Thus, loss of PTEN alone is not sufficient for cells to become cancerous, therefore other developmental events are necessary for tumor formation. [ABSTRACT FROM AUTHOR]

Abstract: Peculiar oscillating convection is observed when two-dimensional double-diffusive convection in porous medium is analysed numerically. The top and bottom walls of an enclosure are insulated, and constant and opposing heat and mass fluxes are prescribed on the vertical walls. The peculiar oscillations are of three types: (1) Chaotic oscillations wherein the main flow is due to temperature; however, the convection due to concentration is strong enough to generate this peculiar oscillation. (2) The ‘sudden steady state case’ caused by the shifts from thermally-driven to concentration-driven forces. (3) The ‘re-oscillation case’ caused by the convection pattern changes from centrosymmetric to non-centrosymmetric. [Copyright &y& Elsevier]

Abstract: Molecular dynamics (MD) simulations confirm that normal grain boundary (GB) motion must often be coupled to tangential translation of grains and will then produce shear deformation of the lattice traversed by the GB. Conversely, shear stresses applied to a GB can induce its normal motion. Using [001] symmetrical tilt GBs in copper as a model, the coupling factor β between the GB motion and grain translations has been calculated by MD simulations over the entire misorientation range and a wide range of temperatures. The coupling factor is multivalued, can be positive or negative, and shows an abrupt switch from one branch to another at a tilt angle of about 35°. At high temperatures the response of high-angle GBs to shear changes from coupling to sliding until coupling disappears. No sliding is observed for low-angle GBs up to near the melting point. A geometric model of coupling proposed in this work predicts the misorientation dependence of β in excellent agreement with MD results and relates the multivalued character of β to the point symmetry of the crystal. Two kinds of low-angle GBs with different dislocations occur when the tilt angle is small and again when it approaches 90°. In these limits, the multiplicity of β is explained by different Burgers vectors of the dislocations. The results of this work are summarized as a temperature–misorientation diagram of mechanical responses of GBs. Unsolved problems and future work in this area are discussed. [Copyright &y& Elsevier]

Abstract: The adsorption of ovalbumin (OA) onto the bubble surfaces was studied with various pHs (3.5, 4.6, 6.0 and 8.0) by a continuous foam separation technique. From the value of the saturated surface density of adsorbed OA, the variation of effective diameter (D) of an OA molecule on the bubble surface was estimated for various pHs (3.5, 4.6, 6.0 and 8.0) of the OA solutions, assuming that the cross section of the OA molecules be circular and that the OA molecules adsorb on the bubble surface in a closest packing structure. The estimated variation of D with pH was attempted to explain based on a model modified from that proposed by Pujar and Zydney [N.S. Pujar, A.L. Zydney, J. Chromatogr. A 796 (1998) 229–238]. The modified model could well reproduce the variation of the effective diameter with pH; the values of D calculated on the basis of the modified model almost agreed with that estimated from the saturated surface density in the present experimental pH range. From these, conclusion was drawn that the modified model presented in this study can express the variation in the effective diameter with pH. [Copyright &y& Elsevier]

First, two conditions are specified for the lowest order Wentzel–Kramers–Brillouin quantization rule to yield exact results. These rules are related to the periodic orbit decomposition of the quantum density of states. This approach is then applied to supersymmetric quantum mechanics. It leads to a new derivation of the result that shape-invariant potentials give exact results when the classical action is calculated with the square of the super potential, but without the Maslov index or the Langer correction.PACS Nos.: 03.65.Sq, 12.60.Jv [ABSTRACT FROM AUTHOR]

There are currently no treatments for salivary gland diseases, making it vital to understand signaling mechanisms operating in acinar and ductal cells so as to develop regenerative therapies. To date, little work has focused on elucidating the signaling cascades controlling the differentiation of these cell types in adult mammals. To analyze the function of the Hippo‐TAZ/YAP1 pathway in adult mouse salivary glands, we generated adMOB1DKO mice in which both MOB1A and MOB1B were TAM‐inducibly deleted when the animals were adults. Three weeks after TAM treatment, adMOB1DKO mice exhibited smaller submandibular glands (SMGs) than controls with a decreased number of acinar cells and an increased number of immature dysplastic ductal cells. The mutants suffered from reduced saliva production accompanied by mild inflammatory cell infiltration and fibrosis in SMGs, similar to the Sjogren's syndrome. MOB1‐deficient acinar cells showed normal proliferation and apoptosis but decreased differentiation, leading to an increase in acinar/ductal bilineage progenitor cells. These changes were TAZ‐dependent but YAP1‐independent. Biochemically, MOB1‐deficient salivary epithelial cells showed activation of the TAZ/YAP1 and β‐catenin in ductal cells, but reduced SOX2 and SOX10 expression in acinar cells. Thus, Hippo‐TAZ signaling is critical for proper ductal and acinar cell differentiation and function in adult mice. [ABSTRACT FROM AUTHOR]

Tomato (Lycopersiconesculentum) seedlings were grown in the presence of cadmium. After 1 week of Cd treatment, a sharp decline in biomass accumulation in the leaves and roots was observed, together with a decrease in the rate of photosynthetic activity due to both Rubisco and chlorophyll degradation and stomata closure. Cadmium induced a significant decrease in nitrate content and inhibition of the activities of nitrate reductase, nitrite reductase, glutamine synthetase (GS) and ferredoxin-glutamate synthase. An increase in NADH-glutamate synthase and NADH-glutamate dehydrogenase activity was observed in parallel. The accumulation of ammonium into the tissues of treated plants was accompanied by a loss of total protein and the accumulation of amino acids. Gln represented the major amino acid transported through xylem sap of Cd-treated and control plants. Cadmium treatment increased the total amino acid content in the phloem, maintaining Gln/Glu ratios. Western and Northern blot analysis of Cd-treated plants showed a decrease in chloroplastic GS protein and mRNA and an increase in cytosolic GS and glutamate dehydrogenase transcripts and proteins. An increase in asparagine synthetase mRNA was observed in roots, in parallel with a strong increase in asparagine. Taken together, these results suggest that the plant response to Cd stress involved newly induced enzymes dedicated to coordinated leaf nitrogen remobilization and root nitrogen storage. [ABSTRACT FROM AUTHOR]

Examines the possibility that the rapid death of β cells is attributable to apoptosis for some axotomized retinal ganglion cells. Proportion of pyknotic cells in Nissl-stained cat retinas; Survival of axotomized β cells after the intravitreal injection of caspase 3 inhibitor; Discussion on whether the time course of the occurrence of pyknotic cells corresponds to the sharp death period of β cells.

Viral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children. A cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated. Overall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1–2.8), human metapneumovirus (2.1, 1.4–3.2), rhinovirus (2.1, 1.8–2.6), and respiratory syncytial virus (1.6, 1.2–1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0–4.9). We determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections. [ABSTRACT FROM AUTHOR]

A single SH group in the B chain (33 kDa), generated by the specific reduction of the single interchain SS bond of human urinary urokinase, was alkylated (UK · B) with iodoacetamide to prevent a spontaneous SH-SS interchange. An SS bond in UK · B was exclusively alkylated with iodoacetamide (R · CAM-UK · B) after reduction with dithiothreitol in 0.3 M guanidine · HCl in the presence of the competitive inhibitor N&alpha:-benzoyl-L-argininamide with concomitant loss of 65-68% of the esterolytic activity towards N-acetyl-glycyl-L-lysine methyl ester. This specific SS bond was located at Cys194-Cys222 whose SS loop contained the active-site Ser198, as determined by amino acid analyses and identification of the N and C termini of the tryptic digest. Transformation of UK · B into R · CAM-UK · B induced no shift of the optimal pH in the bell-shaped pH/activity profile; pH values for 50% activity were similar (pH 9.7) for 10-min alkalization of the enzyme but different between UK · B (pH 9.4) and R · CAM-UK · B (pH 8.8) for 18-h alkalization. An unaltered Km value and a decline by 64% in k... in the esterolytic activity indicate that the pretransition Michaelis complex is formed without degeration of the primary substrate-binding site, but the catalytic pathway thereafter has deteriorated. In affinity labeling with dansyl chloride or Nalpha;-tosyl-L-lysine chloromethylketone, which interrupted the catalysis at the latest at a stage involving the abortive acyl intermediate, the second-order rate constant for UK · B was lowered to 28% or 35% for R · CAM-UK · B, respectively, but the labeling yields were similar. The results indicate that indispensable structural elements, such as the catalytic triad and oxyanion hole, are maintained but a local conformation, which is necessary for efficient transition to the acyl intermediate and/or for resistance against alkaline inactivation, is destabilized with Cys194-Cys222 scission. [ABSTRACT FROM AUTHOR]

Purpose: Self-stigma negatively influences self-esteem, quality of life, self-efficacy, treatment adherence, and recovery in psychiatric patients. By revealing personality traits that influence self-stigma, we can gain useful knowledge for the management of self-stigma. A previous meta-analysis indicated that patients with schizophrenia have higher scores on the Autism-Spectrum Quotient (AQ) than healthy controls. However, the relationship between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders remains unclear. Therefore, the present study aimed to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. Patients and Methods: We recruited 127 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, and delusional disorder). We assessed participants' self-stigma and autistic symptoms using the Internalized Stigma for Mental Illness (ISMI) scale and the Autism-Spectrum Quotient (AQ), respectively. The differences in the scores of ISMI and AQ according to patient characteristics were investigated. Multiple regression analysis controlling for age and gender was performed to determine the relationship between the total scores on the AQ and IMSI scale. Results: Female patients showed a higher level of self-stigma than males. Unmarried patients showed a significantly higher score on the AQ than married patients. Multiple regression analysis adjusted for age and gender indicated that the total score on AQ might be a predictor of the overall rating on ISMI in patients with schizophrenia spectrum disorders. Conclusion: This study is the first to reveal the association between autistic symptoms and self-stigma in patients with schizophrenia spectrum disorders. Our results highlight the importance of considering autistic symptoms in the assessment and management of self-stigma in patients with schizophrenia spectrum disorders. [ABSTRACT FROM AUTHOR]

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer, accounting for 3% of all lung cancers. The prognosis is poor and the standard therapy has not been well established. Herein, we report a case of advanced LCNEC of the lung that responded to nivolumab. The patient was a 62-year old man with stage IVB LCNEC of the lung. The disease progressed following the administration of second-line chemotherapy, and he was treated with nivolumab 3 mg/kg as the third-line treatment. Although treatment was ceased after two cycles due to interstitial pneumonia, the disease remained stable for approximately six months under observation. There was no other adverse event related to nivolumab. Following patient mortality from tumor progression, PD-L1 expression was observed to be negative (tumor proportion score <1%) by a re-examination of the primary biopsy specimen. The case herein suggests that nivolumab may be a possible treatment option for LCNEC. [ABSTRACT FROM AUTHOR]

Cell competition is a biological process by which unfit cells are eliminated from "cell society." We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by "normal" MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition. [ABSTRACT FROM AUTHOR]

Subgraph reconfiguration is a family of problems focusing on the reachability of the solution space in which feasible solutions are subgraphs, represented either as sets of vertices or sets of edges, satisfying a prescribed graph structure property. Although there has been previous work that can be categorized as subgraph reconfiguration , most of the related results appear under the name of the property under consideration; for example, independent set, clique, and matching. In this paper, we systematically clarify the complexity status of subgraph reconfiguration with respect to graph structure properties. [ABSTRACT FROM AUTHOR]

RalGTPase-activating protein (RalGAP) is an important negative regulator of small GTPases RalA/B that mediates various oncogenic signaling pathways in various cancers. Although the Ral pathway has been implicated in prostate cancer (PCa) development and progression, the significance of RalGAP in PCa has been largely unknown. We examined RalGAPα2 expression using immunohistochemistry on two independent tissue microarray sets. Both datasets demonstrated that the expression of RalGAPα2 was significantly downregulated in PCa tissues compared to adjacent benign prostatic epithelia. Silencing of RalGAPα2 by short hairpin RNA enhanced migration and invasion abilities of benign and malignant prostate epithelial cell lines without affecting cell proliferation. Exogenous expression of wild-type RalGAP, but not the GTPase-activating protein activity-deficient mutant of RalGAP, suppressed migration and invasion of multiple PCa cell lines and was phenocopied by pharmacological inhibition of RalA/B. Loss of Ralgapa2 promoted local microscopic invasion of prostatic intraepithelial neoplasia without affecting tumor growth in a Pten -deficient mouse model for prostate tumorigenesis. Our findings demonstrate the functional significance of RalGAP downregulation to promote invasion ability, which is a property necessary for prostate carcinogenesis. Thus, loss of RalGAP function has a distinct role in promoting progression from prostatic intraepithelial neoplasia to invasive adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Several inactivated enterovirus-A71 (EV-A71) vaccines are currently licensed in China; however, the development of additional EV-A71 vaccines is ongoing, necessitating extensive analysis of the molecular epidemiology of the virus worldwide. Until 2012, laboratory confirmation of EV-A71 for hand, foot, and mouth disease (HFMD) and other associated diseases had not occurred in the Philippines. Because EV-A71 has been linked with cases of acute flaccid paralysis (AFP), AFP surveillance is one strategy for documenting its possible circulation in the country. To expand current knowledge on EV-A71, molecular epidemiologic analysis and genetic characterization of EV-A71 isolates were performed in this study.Methods: A retrospective study was performed to identify and characterize nonpolio enteroviruses (NPEVs) associated with AFP in the Philippines, and nine samples were found to be EV-A71-positive. Following characterization of these EV-A71 isolates, the complete viral protein 1 (VP1) gene was targeted for phylogenetic analysis.Results: Nine EV-A71 isolates detected in 2000 (n = 2), 2002 (n = 4), 2005 (n = 2), and 2010 (n = 1) were characterized using molecular methods. Genomic regions spanning the complete VP1 region were amplified and sequenced using specific primers. Phylogenetic analysis of the full-length VP1 region identified all nine EV-A71 Philippine isolates as belonging to the genogroup C lineage, specifically the C2 cluster. The result indicated a genetic linkage with several strains isolated in Japan and Taiwan, suggesting that strains in the C2 cluster identified in the Asia-Pacific region were circulating in the Philippines.Conclusion: The study presents the genetic analysis of EV-A71 in the Philippines. Despite some limitations, the study provides additional genetic data on the circulating EV-A71 strains in the Asia-Pacific region, in which information on EV-A71 molecular epidemiology is incomplete. Considering that EV-A71 has a significant public health impact in the region, knowledge of its circulation in each country is important, especially for formulating vaccines covering a wide variety of strains. [ABSTRACT FROM AUTHOR]

Mammalian STE20‐like protein kinase 1/2 (MST1/2) and nuclear Dbf2‐related kinase 1/2 (NDR1/2) are core components of Hippo signaling that are also known to be important regulators of lymphocyte trafficking. However, little is understood about the roles of other Hippo pathway molecules in these cells. Here, we present the first analysis of the function of Mps one binder kinase activator‐1 (MOB1) in T lymphocytes in vivo. T‐cell‐specific double knockout (DKO) of MOB1A/B in mice [tMob1 DKO mice] reduces the number of naïve T cells in both the circulation and secondary lymphoid organs, but leads to an accumulation of CD4+CD8− and CD4−CD8+ single‐positive (SP) cells in the thymus. In vitro, naïve MOB1A/B‐deficient T cells show increased apoptosis and display impaired trafficking capacity in response to the chemokine CCL19. These defects are linked to suppression of the activation of MST and NDR kinases, but are independent of the downstream transcriptional co‐activator Yes‐associated protein 1 (YAP1). Thus, MOB1 proteins play an important role in thymic egress and T‐cell survival that is mediated by a pathway other than conventional Hippo‐YAP1 signaling. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is one of the main viral causes of lower respiratory tract illness (LRTI), especially in young children. RSV vaccines, including maternal and infant vaccines, are under development; however, more epidemiological studies are needed to develop effective vaccination strategies. Objectives: To estimate detailed age‐specific incidence rates and severity of RSV‐associated LRTI (RSV‐LRTI) using data from a community‐based prospective cohort study in the Philippines. Patients/Methods: Cohort children who visited health facilities due to acute respiratory symptoms were identified, and nasopharyngeal swabs were collected to detect RSV. The severity of RSV‐LRTI was assessed using the severity definition proposed by the World Health Organization. Risk factors for developing RSV‐LRTI and contribution of SpO2 measurement were also evaluated. Results: A total of 395 RSV episodes which occurred in children aged 2‐59 months were categorised as 183 RSV‐LRTI, 72 as severe RSV‐LRTI and 29 as very severe RSV‐LRTI. Children aged 3‐5 months had the highest incidence rate of RSV‐LRTI, at 207.4 per 1000 child‐years (95% CI: 149.0‐279.5). Younger age group, place of living and low educational level of caregivers were associated with developing RSV‐LRTI. Clinical manifestations had low levels of agreement with hypoxaemia as measured by pulse oximeter. Conclusion: The highest burden of RSV was observed in young infants aged 3‐5 months, whereas the burden was also high in those aged 12‐20 months. Future vaccination strategies should consider the protection of older children, especially those aged one year, as well as young infants. [ABSTRACT FROM AUTHOR]

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder. [ABSTRACT FROM AUTHOR]

FEAT, the protein encoded by methyltransferase‐like 13 (METTL13), is aberrantly upregulated in most human cancers and potently drives tumorigenesis in vivo; however, its role in normal tissues remains elusive. Immunoblotting has displayed weak FEAT expression in normal human tissues, including the testis. Here, we found that FEAT is expressed in fetal and adult Leydig cells in the testis. FEAT knockdown using siRNA increased primary cilia formation in MA‐10 Leydig tumor cells, accompanied by enhanced 5′ adenosine monophosphate‐activated protein kinase (AMPK) activation. Immunofluorescence analyses of FEAT‐silenced MA‐10 cells showed diminished insulin‐like factor 3 (INSL3) expression. A male Mettl13+/− mouse developed bilateral intraabdominal cryptorchidism, suggesting defective INSL3 production by fetal Leydig cells. Leydig cells from the mouse showed markedly decreased INSL3 protein by immunohistochemistry. Together, these results suggest that FEAT facilitates the INSL3 production in testicular Leydig cells that is essential for transabdominal testis migration. FEAT (METTL13) is expressed in fetal and adult Leydig cells in the testis. FEAT‐silenced MA‐10 Leydig cells showed diminished INSL3 protein. A male Mettl13+/− mouse exhibited bilateral intraabdominal cryptorchidism and markedly decreased INSL3 expression in Leydig cells. [ABSTRACT FROM AUTHOR]

Despite a general view that asparagine synthetase generates asparagine as an amino acid for long-distance transport of nitrogen to sink organs, its role in nitrogen metabolic pathways in floral organs during seed nitrogen filling has remained undefined. We demonstrate that the onset of pollination in Arabidopsis induces selected genes for asparagine metabolism, namely ASN1 ( At3g47340), GLN2 ( At5g35630), GLU1 ( At5g04140), Aap AT2 ( At5g19950), ASPGA1 ( At5g08100) and ASPGB1 ( At3g16150), particularly at the ovule stage (stage 0), accompanied by enhanced asparagine synthetase protein, asparagine and total amino acids. Immunolocalization confined asparagine synthetase to the vascular cells of the silique cell wall and septum, but also to the outer and inner seed integuments, demonstrating the post-phloem transport of asparagine in these cells to developing embryos. In the asn1 mutant, aberrant embryo cell divisions in upper suspensor cell layers from globular to heart stages assign a role for nitrogen in differentiating embryos within the ovary. Induction of asparagine metabolic genes by light/dark and nitrate supports fine shifts of nitrogen metabolic pathways. In transgenic Arabidopsis expressing promoter Ca MV 35S:: ASN1 fusion, marked metabolomics changes at stage 0, including a several-fold increase in free asparagine, are correlated to enhanced seed nitrogen. However, specific promoter Napin2S:: ASN1 expression during seed formation and a six-fold increase in asparagine toward the desiccation stage result in wild-type seed nitrogen, underlining that delayed accumulation of asparagine impairs the timing of its use by releasing amide and amino nitrogen. Transcript and metabolite profiles in floral organs match the carbon and nitrogen partitioning to generate energy via the tricarboxylic acid cycle, GABA shunt and phosphorylated serine synthetic pathway. [ABSTRACT FROM AUTHOR]

The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements. In this review, we attempt to systematically summarize results that have been gleaned from detailed in vivo characterizations of these mutants. Our goal is to describe the physiological roles of Hippo signaling in several normal organ systems, as well as to emphasize how disruption of the Hippo pathway, and particularly hyperactivation of YAP1/ TAZ, can be oncogenic. [ABSTRACT FROM AUTHOR]

Ferredoxin:NADP(H) oxidoreductase (FNR) plays a key role in redox metabolism in plastids. Whereas leaf FNR (LFNR) is required for photosynthesis, root FNR (RFNR) is believed to provide electrons to ferredoxin (Fd)- dependent enzymes, including nitrite reductase (NiR) and Fd-glutamine-oxoglutarate aminotransferase (Fd-GOGAT) in non-photosynthetic conditions. In some herbal species, however, most nitrate reductase activity is located in photosynthetic organs, and ammonium in roots is assimilated mainly by Fd-independent NADH-GOGAT. Therefore, RFNR might have a limited impact on N assimilation in roots grown with nitrate or ammonium nitrogen sources. AtRFNR genes are rapidly induced by application of toxic nitrite. Thus, we tested the hypothesis that RFNR could contribute to nitrite reduction in roots by comparing Arabidopsis thaliana seedlings of the wild type with lossof- function mutants of RFNR2. When these seedlings were grown under nitrate, nitrite or ammonium, only nitrite nutrition caused impaired growth and nitrite accumulation in roots of rfnr2. Supplementation of nitrite with nitrate or ammonium as N sources did not restore the root growth in rfnr2. Also, a scavenger for nitric oxide (NO) could not effectively rescue the growth impairment. Thus, nitrite toxicity, rather than N depletion or nitrite-dependent NO production, probably causes the rfnr2 root growth defect. Our results strongly suggest that RFNR2 has a major role in reduction of toxic nitrite in roots. A specific set of genes related to nitrite reduction and the supply of reducing power responded to nitrite concomitantly, suggesting that the products of these genes act co-operatively with RFNR2 to reduce nitrite in roots. [ABSTRACT FROM AUTHOR]

Suppose that we are given two dominating sets D s and D t of a graph G whose cardinalities are at most a given threshold k . Then, we are asked whether there exists a sequence of dominating sets of G between D s and D t such that each dominating set in the sequence is of cardinality at most k and can be obtained from the previous one by either adding or deleting exactly one vertex. This decision problem is known to be PSPACE-complete in general. In this paper, we study the complexity of this problem from the viewpoint of graph classes. We first prove that the problem remains PSPACE-complete even for planar graphs, bounded bandwidth graphs, split graphs, and bipartite graphs. We then give a general scheme to construct linear-time algorithms and show that the problem can be solved in linear time for cographs, forests, and interval graphs. Furthermore, for these tractable cases, we can obtain a desired sequence if it exists such that the number of additions and deletions is bounded by O ( n ) , where n is the number of vertices in the input graph. [ABSTRACT FROM AUTHOR]

Selecting the best quantitative PCR assay is essential to detect human norovirus genome effectively from clinical and environmental samples because no cell lines have been developed to propagate this virus. The real-time PCR methods for noroviruses GI (4 assays) and GII (3 assays) were evaluated using wastewater (n = 70) and norovirus-positive stool (n = 77) samples collected in Japan between 2012 and 2013. Standard quantitative PCR assays recommended by the U.S. Environmental Protection Agency, International Organization for Standardization, and Ministry of Health, Labour and Welfare, Japan, together with recently reported assays were included. Significant differences in positive rates and quantification cycles were observed by non-parametric analysis. The present study identifies the best assay for norovirus GI and GII to amplify norovirus genomes efficiently. [ABSTRACT FROM AUTHOR]

The local and global transmission dynamics of influenza B virus is not completely understood mainly because of limited epidemiological and sequence data for influenza B virus. Here we report epidemiological and molecular characteristics of influenza B viruses from 2010 to 2013 in Leyte Island, Philippines. Phylogenetic analyses showed global dissemination of the virus among both neighboring and distant areas. The analyses also suggest that southeast Asia is not a distributor of influenza B virus and can introduce the virus from other areas. Furthermore, we found evidence on the local persistence of the virus over years in the Philippines. Taken together, both local persistence and global dissemination play a significant role in the circulation of influenza B virus. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05) and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines. [ABSTRACT FROM AUTHOR]

Consider a puzzle consisting of n tokens on an n -vertex graph, where each token has a distinct starting vertex and a distinct target vertex it wants to reach, and the only allowed transformation is to swap the tokens on adjacent vertices. We prove that every such puzzle is solvable in O ( n 2 ) token swaps, and thus focus on the problem of minimizing the number of token swaps to reach the target token placement. We give a polynomial-time 2-approximation algorithm for trees, and using this, obtain a polynomial-time 2 α -approximation algorithm for graphs whose tree α -spanners can be computed in polynomial time. Finally, we show that the problem can be solved exactly in polynomial time on complete bipartite graphs. [ABSTRACT FROM AUTHOR]

Pneumonia is a leading cause of deaths in infants and young children in developing countries, including the Philippines. However, data at the community level remains limited. Our study aimed to estimate incidence and mortality rates and to evaluate risk factors and health-seeking behavior for childhood pneumonia. A household level interview survey was conducted in Biliran Island, the Philippines. Caregivers were interviewed using a semi-structured questionnaire to check if children had symptoms suggesting pneumonia-like episodes from June 2011 to May 2012. Of 3,327 households visited in total, 3,302 (99.2%) agreed to participate, and 5,249 children less than 5 years of age were included in the study. Incidence rates of pneumonia-like episodes, severe pneumonia-like episodes, and pneumonia-associated mortality were 105, 61, and 0.9 per 1,000 person-years, respectively. History of asthma [hazard ratio (HR): 5.85, 95% confidence interval (CI): 4.83–7.08], low socioeconomic status (SES) (HR: 1.11, 95% CI: 1.02–1.20), and long travel time to the healthcare facility estimated by cost distance analysis (HR: 1.32, 95% CI: 1.09–1.61) were significantly associated with the occurrence of pneumonia-like episodes by the Cox proportional hazards model. For severe pneumonia-like episodes, a history of asthma (HR: 8.39, 95% CI: 6.54–10.77) and low SES (HR: 1.30, 95% CI: 1.17–1.45) were significant risk factors. Children who had a long travel time to the hospital were less likely to seek hospital care (Odds ratio: 0.32, 95% CI: 0.19–0.54) when they experienced severe pneumonia-like episodes. Incidence of pediatric pneumonia-like episodes was associated with a history of asthma, SES, and the travel time to healthcare facilities. Travel time was also identified as a strong indicator for health-seeking behavior. Improved access to healthcare facilities is important for early and effective management. Further studies are warranted to understand the causal relationship between asthma and pneumonia. [ABSTRACT FROM AUTHOR]

This study aimed to determine the role of influenza-like illness (ILI) surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6%) cases. Among the cases sampled, 1,637 (75.6%) were children aged <5 years. 874 (43.0%) cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV) were predominantly detected (both were 25.7%) followed by human rhinovirus (HRV) (17.5%). The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%). In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively. [ABSTRACT FROM AUTHOR]

The molecular mechanisms of endothelial dysfunction and vascular calcification have been considered independently and potential links are currently unknown in chronic kidney disease (CKD). Bone morphogenetic protein (BMP) receptor signaling mediates calcification of atherosclerotic plaques. Here we tested whether BMP receptor signaling contributes to endothelial dysfunction, as well as to osteogenic differentiation of vascular smooth muscle cells (VSMCs), in a model of short-term CKD. In C57BL/6 mice, subtotal nephrectomy activated BMP receptor and increased phosphatase-and-tensin homolog (PTEN) protein in the endothelial cells and medial VSMCs without vascular remodeling in the aorta. In the endothelial cells, PTEN induction led to inhibition of the Akt-endothelial nitric oxide synthase (eNOS) pathway and endothelial dysfunction. In VSMCs, the PTEN increase induced early osteogenic differentiation. CKD-induced inhibition of eNOS phosphorylation and the resultant endothelial dysfunction were inhibited in mice with endothelial cell-specific PTEN ablation. Knockout of the BMP type I receptor abolished endothelial dysfunction, the inhibition of eNOS phosphorylation, and VSMC osteogenic differentiation in mice with CKD. A small molecule inhibitor of BMP type I receptor, LDN-193189, prevented endothelial dysfunction and osteogenic differentiation in CKD mice. Thus, BMP receptor activation is a mechanism for endothelial dysfunction in addition to vascular osteogenic differentiation in a short-term CKD model. PTEN may be key in linking BMP receptor activation and endothelial dysfunction in CKD. [ABSTRACT FROM AUTHOR]

Background Hepatitis E virus (HEV) infection is a significant public health concern in Asia, and swine is an important source of sporadic HEV infection in human. However, no epidemiological data are available regarding HEV infection among the swine or human population in the Philippines. To assess the HEV infection status among pigs in rural areas, we investigated the molecular characteristics and seroprevalence of HEV among household-raised pigs in San Jose, Tarlac Province, the Philippines. Result Serum and rectal swab samples were collected from 299 pigs aged 2-24 months from 155 households in four barangays (villages) between July 2010 and June 2011. Enzyme-linked immunosorbent assay (ELISA) revealed that 50.3% [95% confidence interval (CI) 44.5-56.2%] and 22.9% (95% CI 18.2-28.1%) of pigs tested positive for anti-HEV IgG and IgM, respectively. HEV RNA was detected in the feces of 22 pigs (7.4%, 95% CI 4.7-10.9%). A total of 103 households (66.5%, 95% CI 58.4-73.8%) had at least one pig that tested positive for anti-HEV IgG or IgM or HEV RNA. The prevalence of anti-HEV IgG and IgM in breeding pig (8-24 months) were higher than that in growing pigs (2-4 months) (p < 0.0001 and p = 0.008, respectively). HEV RNA was more frequently detected in 2-4-month-old pigs (9.2%, 95% CI 5.4-14.6%) than in ⩾5-month-old pigs (4.8%, 95% CI 1.1-8.5%) without statistical significance (p = 0.142). HEV RNA showed 0-27.6% nucleotide difference at the partial ORF2 gene among the detected viruses, and a majority of them belonged to subtype 3a (20/22, 90.9%). Conclusion We found a high prevalence of HEV antibodies in the household-raised pig population in rural areas of the Philippines, which indicates the potential risk of HEV infection among local residents. Only genotype 3 of HEV was observed, and genetically diverse strains of HEV were found to be circulating in pigs in this study. [ABSTRACT FROM AUTHOR]

Inflammation has a critical role in the development of insulin resistance. Recent evidence points to a contribution by the central nervous system in the modulation of peripheral inflammation through the anti-inflammatory reflex. However, the importance of this phenomenon remains elusive in type 2 diabetes pathogenesis. Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene encoding a negative regulator of PI3K signaling, led to activation of the cholinergic anti-inflammatory pathway that is mediated by M2 activated macrophages in peripheral tissues. As such, Rip-cre+ Ptenflox/flox mice showed lower systemic inflammation and greater insulin sensitivity under basal conditions compared to littermate controls, which were abolished when the mice were treated with an acetylcholine receptor antagonist or when macrophages were depleted. After feeding with a high-fat diet, the Pten-deleted mice remained markedly insulin sensitive, which correlated with massive subcutaneous fat expansion. They also exhibited more adipogenesis with M2 macrophage infiltration, both of which were abolished after disruption of the anti-inflammatory efferent pathway by left vagotomy. In summary, we show that Pten expression in Rip+ neurons has a critical role in diabetes pathogenesis through mediating the anti-inflammatory reflex. [ABSTRACT FROM AUTHOR]

In a genome-wide small interfering RNA(siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) as a factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I·C)-induced inhibition of VSV replication. Promoter-driven reporter gene assays demonstrated that IFI35 overexpression suppressed the activation of IFN-βand ISG56 promoters, whereas its depletion had the opposite effect. Further investigation revealed that IFI35 specifically interacted with retinoic acid-inducible gene I (RIG-I) and negatively regulated its activation through mechanisms that included (i) suppression of dephosphorylation (activation) of RIG-I and (ii) proteasome-mediated degradation of RIG-I via K48-linked ubiquitination. Overall, the results presented here suggest a novel role for IFI35 in negative regulation of RIG-I-mediated antiviral signaling, which will have implications for diseases associated with excessive immune signaling. IMPORTANCE Mammalian cells employ a variety of mechanisms, including production of interferons (IFNs), to counteract invading pathogens. In this study, we identified a novel role for a cellular protein, IFN-inducible protein 35 (IFP35/IFI35), in negatively regulating the host IFN response during vesicular stomatitis virus (VSV) infection. Specifically, we found that IFI35 inhibited activation of the RNA sensor, the retinoic acid-inducible gene I (RIG-I), leading to inhibition of IFN production and thus resulting in better replication of VSV. The identification of a cellular factor that attenuates the IFN response will have implications toward understanding inflammatory diseases in humans that have been found to be associated with defects in the regulation of host IFN production, such as systemic lupus erythematosus and psoriasis. [ABSTRACT FROM AUTHOR]

Abstract: We have focused on a protic ionic liquid, ethylimidazolium bis(trifluoromethanesulfonyl)amide ([eimH][Tf2N]), and the analogous aprotic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide ([emim][Tf2N]). Densities, viscosities, and electrical conductivities of the two ionic liquids have been measured over the temperature range T =(273.15–363.15)K at atmospheric pressure. The densities of [eimH][Tf2N] and [emim][Tf2N] decrease with increasing temperature. The protic ionic liquid has the higher density (the smaller molar volume) than the aprotic one. The transport properties of the two ionic liquids show ordinary temperature dependencies. [eimH][Tf2N] has the higher viscosities (smaller electrical conductivities) than [emim][Tf2N]. Empirical Walden products indicate that [eimH][Tf2N] shows smaller conductivities than [emim][Tf2N] at certain viscosities. To investigate CO2 absorption properties of the ionic liquids, binary phase equilibria in CO2 +ionic liquid systems have been investigated under high pressures up to 6MPa at T =(298.15, 313.15, 333.15)K. The solubilities of CO2 in [eimH][Tf2N] and [emim][Tf2N] show typical pressure dependencies in both mole fraction and molarity scales as physical absorbents. The mole fraction of CO2 in [eimH][Tf2N] is slightly smaller than that in [emim][Tf2N] under the conditions investigated, while the molarity of CO2 in [eimH][Tf2N] is comparable to that in [emim][Tf2N]. The molar volumes in ionic liquid phase almost linearly decrease with the mole fraction of CO2 in the present systems. The partial molar volume of CO2 in [eimH][Tf2N] at infinite dilution is almost same as that in [emim][Tf2N]. [Copyright &y& Elsevier]

Abstract: The pressure–volume–temperature–composition relations for CO2 +pyrrolidinium-based ionic liquid systems were measured over the pressure range up to 6MPa at T =(298.15, 313.15, 333.15)K. Three ionic liquids were studied in the present work: N-methyl-N-propylpyrrolidinium bis(trifluoromethanesulfonyl)amide ([Pyr13][TFSA]), N-methoxymethyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)amide ([Pyr1,1O1][TFSA]), and N-methoxymethyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide ([Pyr1,1O1][FSA]). The pressure dependence of CO2 solubility indicates that CO2 molecules are dissolved physically in the three ionic liquids. The mole fraction scaled solubility of CO2 in [Pyr1,1O1][TFSA] is almost the same as that in [Pyr13][TFSA], and [Pyr1,1O1][FSA] showed the smallest solubility at certain pressures and temperatures. On the other hand, the molarity scaled solubility of CO2 in [Pyr1,1O1][TFSA] was nearly equal to that in [Pyr1,1O1][FSA]. The CO2 solubility of [Pyr13][TFSA] was smaller than the other two ionic liquids. The molar volume and density of ionic liquid phase decrease monotonically with an increase of mole fraction of CO2. The volume expansion of liquid phase was not almost dependent of temperature but composition of CO2 under the conditions investigated. [Copyright &y& Elsevier]

Abstract: The densities, viscosities, and electrical conductivities of N-(2-hydroxyethyl) pyridinium bis(trifluoromethanesulfonyl)amide ([Py2OH][Tf2N]) have been measured over the temperature range T =273.15–363.15K at atmospheric pressure. The pressure–volume–temperature–composition relations in the CO2 +[Py2OH][Tf2N] system have been obtained under the pressure condition up to 5MPa at T =298.15, 313.15, and 333.15K. The densities and transport properties were well reproduced with a second order polynomial and Vogel–Fulcher–Tamman equations, respectively. The Walden plot (double logarithm graph of molar conductivity vs reciprocal viscosity) gives the straight line. [Py2OH][Tf2N] has higher densities and poor transport properties compared to an analog without the hydroxyl group, N-butylpyridinium bis(trifluoromethanesulfonyl)amide. The CO2 solubilities in [Py2OH][Tf2N] show typical pressure dependencies in both mole fraction and molarity scales as a physical absorbent. The molar volume in the liquid [Py2OH][Tf2N] phase decreases by the dissolution of CO2. The volume of ionic liquid phase expands with an increase of CO2. As a result, the saturated liquid density slightly decreases over the present conditions investigated. [Copyright &y& Elsevier]

Abstract: We have determined the electrical conductivity in CO2-saturated 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim][PF6]) at 298.1, 313.1 and 333.1K as a function of CO2 pressure. Moreover, self-diffusion coefficients of cation and anion in CO2-saturated [C4mim][PF6] have been measured at high pressures up to ∼15MPa and at a fixed temperature of 333.2K by 1H and 19F NMR using the pulsed field gradient spin-echo method. As CO2 dissolves in [C4mim][PF6], marked increases in all the three transport quantities were observed at lower pressure, and then they showed very slight changes at higher pressure. The correlation between the conductivity and the ionic diffusion coefficients has been discussed. [Copyright &y& Elsevier]

Induced pluripotent stem cells (iPSCs) can be generated from patients with specific diseases by the transduction of reprogramming factors and can be useful as a cell source for cell transplantation therapy for various diseases with impaired organs. However, the low efficiency of iPSC derived from somatic cells (0.01-0.1%) is one of the major problems in the field. The phosphoinositide 3-kinase (PI3K) pathway is thought to be important for self-renewal, proliferation, and maintenance of embryonic stem cells (ESCs), but the contribution of this pathway or its well-known negative regulator, phosphatase, and tensin homolog deleted on chromosome ten (Pten), to somatic cell reprogramming remains largely unknown. Here, we show that activation of the PI3K pathway by the Pten inhibitor, dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate, improves the efficiency of germline-competent iPSC derivation from mouse somatic cells. This simple method provides a new approach for efficient generation of iPSCs. [ABSTRACT FROM AUTHOR]

The metabolism of membrane phosphoinositides is critical for a variety of cellular processes. Phosphatidylinositol-3,5-bisphosphate [Ptdlns(3,5)P2] controls multiple steps of the intracellular membrane trafficking system in both yeast and mammalian cells. However, other than in neuronal tissues, little is known about the physiological functions of Ptdlns(3,5)P2 in mammals. Here, we provide genetic evidence that type III phosphatidylinositol phosphate kinase (PIPKIII), which produces PtdIns(3,5)P2, is essential for the functions of polarized epithelial cells. PIPKIII-null mouse embryos die by embryonic day 8.5 because of a failure of the visceral endoderm to supply the epiblast with maternal nutrients. Similarly, although intestine-specific PIPKIII-deficient mice are born, they fail to thrive and eventually die of malnutrition. At the mechanistic level, we show that PIPKIII regulates the trafficking of proteins to a cell's apical membrane domain. Importantly, mice with intestine-specific deletion of PIPKIII exhibit diarrhea and bloody stool, and their gut epithelial layers show inflammation and fibrosis, making our mutants an improved model for inflammatory bowel diseases. In summary, our data demonstrate that PIPKIII is required for the structural and functional integrity of two different types of polarized epithelial cells and suggest that Ptdlns(3,5)P2 metabolism is an unexpected and critical link between membrane trafficking in intestinal epithelial cells and the pathogenesis of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background Hepcidin is associated with iron-restricted erythropoiesis. A previous cross-sectional study showed that serum hepcidin-25 levels are negatively associated with the hemoglobin concentration in non-dialysis chronic kidney disease (CKD) patients with sufficient iron stores. This longitudinal study aimed at ascertaining the association between hepcidin-25 levels and the progression of renal anemia. Methods We selected 335 non-dialysis CKD patients who showed hemoglobin concentrations >10 g/dL and who were not receiving erythropoiesis-stimulating agent (ESA) therapy, from among the subjects of our previous study, who had been recruited between February and June 2007 in a previous study. The primary outcome was the start of the ESA therapy or hemoglobin concentrations remaining below 10 g/dL for >3 months, by 31 December 2010. The patients were classified into high- and low-ferritin groups depending on their median ferritin levels. The Cox proportional hazard model with restricted cubic spline curve analysis was used to determine the association between hepcidin-25 levels and the outcome for each group. Results The hepcidin-25 level was a significant predictor both for the high-ferritin group (P = 0.04, linearity = 0.02) and for the low-ferritin group (P = 0.04, linearity P = 0.02). The spline curve for the high-ferritin group showed that higher hepcidin-25 levels had a high log-relative hazard. Conclusions Higher hepcidin-25 levels predict the progression of anemia in non-dialysis CKD patients with sufficient iron stores, indicating the involvement of hepcidin in the progression of anemia in non-dialysis CKD patients. [ABSTRACT FROM PUBLISHER]

Please cite this paper as: Burmaa et al. (2012) Cumulative incidence of pandemic influenza A (H1N1) 2009 by a community-based serological cohort study in Selenghe Province, Mongolia. Influenza and Other Respiratory Viruses 6(601), e97-e104. Background Large community outbreaks of pandemic A (H1N1) 2009 occurred between October and December 2009 in Mongolia. A serological study was conducted among the general population by testing paired sera collected before and after the first wave of pandemic in Selenghe province, Mongolia. None of the study participants had been vaccinated for pandemic A (H1N1) 2009 before the second samples were collected. Objective The objective of this study was to estimate cumulative incidence of pandemic A (H1N1) 2009 in different age-groups of Selenghe province residents. Methods After informed consent was obtained from apparently healthy volunteers, the paired sera and background information were collected. Antibody titers were measured using hemagglutinin inhibition (HI) and microneutralization (MN) assays for A/California/07/2009pdm. A fourfold rise in antibody titers was regarded as the evidence of infection. Results The overall cumulative incidences in the study group for all ages were 28·8% (76/264) by HI, 35·2% (93/264) by MN, and 25·0% (66/264) by both HI and MN. Cumulative incidences of infection varied among age-groups, with children aged 2-4 and 5-9 years having high cumulative incidence of infection. Overall cumulative incidences of infection in the whole population were estimated to be 23·0% (4946/21 460) by HI, 30·2% (6473/21 460) by MN, and 18·8% (4036/21 460) by both HI and MN. Conclusions This study indicates that about one-fourth of the total population in Selenghe province was infected with pandemic A (H1N1) 2009 virus during the first wave of the pandemic. [ABSTRACT FROM AUTHOR]

During endochondral bone formation, Sox9 expression starts in mesenchymal progenitors, continues in the round and flat chondrocyte stages at high levels, and ceases just prior to the hypertrophic chondrocyte stage. Sox9 is important in mesenchymal progenitors for their differentiation into chondrocytes, but its functions post-differentiation have not been determined. To investigate Sox9 function in chondrocytes, we deleted mouse Sox9 at two different steps after chondrocyte differentiation. Sox9 inactivation in round chondrocytes resulted in a loss of Col2a1 expression and in apoptosis. Sox9 inactivation in flat chondrocytes caused immediate terminal maturation without hypertrophy and with excessive apoptosis. Inactivation of Sox9 in the last few cell layers resulted in the absence of Col10a1 expression, suggesting that continued expression of Sox9 just prior to hypertrophy is necessary for chondrocyte hypertrophy. SOX9 knockdown also caused apoptosis of human chondrosarcoma SW1353 cells. These phenotypes were associated with reduced Akt phosphorylation. Forced phosphorylation of Akt by Pten inactivation partially restored Col10a1 expression and cell survival in Sox9floxdel/floxdel mouse chondrocytes, suggesting that phosphorylated Akt mediates chondrocyte survival and hypertrophy induced by Sox9. When the molecular mechanism of Sox9-induced Akt phosphorylation was examined, we found that expression of the PI3K subunit Pik3ca (p110a) was decreased in Sox9floxdel/floxdel mouse chondrocytes. Sox9 binds to the promoter and enhances the transcriptional activities of Pik3ca. Thus, continued expression of Sox9 in differentiated chondrocytes is essential for subsequent hypertrophy and sustains chondrocyte-specific survival mechanisms by binding to the Pik3ca promoter, inducing Akt phosphorylation. [ABSTRACT FROM AUTHOR]