Re-annotation of protein-coding genes in 10 complete genomes of Neisseriaceae family by combining similarity-based and composition-based methods.

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Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands

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Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity

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An extended discrete element method for the estimation of contact pressure at the ankle joint during stance phase

Abnormalities in the ankle contact pressure are related to the onset of osteoarthritis. In vivo measurements are not possible with currently available techniques, so computational methods such as the finite element analysis (FEA) are often used instead. The discrete element method (DEM), a computationally efficient alternative to time-consuming FEA, has also been used to predict the joint contact pressure. It describes the articular cartilage as a bed of independent springs, assuming a linearly elastic behaviour and absence of relative motion between the bones. In this study, we present the extended DEM (EDEM) which is able to track the motion of talus over time. The method was used, with input data from a subject-specific musculoskeletal model, to predict the contact pressure in the ankle joint during gait. Results from EDEM were also compared with outputs from conventional DEM. Predicted values of contact area were larger in EDEM than they were in DEM (4.67 and 4.18 cm2, respectively). Peak values of contact pressure, attained at the toe-off, were 7.3 MPa for EDEM and 6.92 MPa for DEM. Values predicted from EDEM fell well within the ranges reported in the literature. Overall, the motion of the talus had more effect on the extension and shape of the pressure distribution than it had on the magnitude of the pressure. The results indicated that EDEM is a valid methodology for the prediction of ankle contact pressure during daily activities

Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis

Alzheimer’s disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10−14), two common variants, GCH1 (rs72713460, P = 4.36 × 10−5 ) and KCNJ15 (rs928771, P = 3.60 × 10−6 ), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype–phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system

Visualization of vortex motion in FeAs-based BaFe<inf>1.9</inf>Ni <inf>0.1</inf>As<inf>2</inf> single crystal by means of magneto-optical imaging

Superconductivity has been found in newly discovered iron-based compounds. This paper studies the motion of magnetic vortices in BaFe1.9Ni 0.1As2 single crystal by means of the magneto-optical imaging technique. A series of magneto-optical images reflecting magnetic flux distribution at the crystal surface were taken when the crystal was zero-field cooled to 10 K. The behavior of the vortices, including penetration into and expulsion from the single crystal with increasing and decreasing external fields, respectively, is discussed. The motion behavior is similar to that observed in high-Tc superconducting cuprates with strong vortex pinning; however, the flux-front is irregular due to randomly distributed defects in the crystal. © 2011 American Institute of Physics

Age-specific incidence rate in severe or symptomatic infection due to pandemic H1N1 2009 influenza virus

Poster Abstract Session - Influenza and H1N1 Diagnosis, Epidemiology, and Viral Outcome: abstract no. 1133BACKGROUND: Age-specific incidence of the 2009 pandemic influenza provides the scientific basis of public health policies and the basic science research on the age-related susceptibility to influenza. While previous epidemiological studies provided vital information for public health policies, most did not incorporate age-specific data of asymptomatic, symptomatic and severe infection in the analysis. In this study, we incorporated data from seroprevalence and microbiologically-confirmed infection to estimate the relative impact of the pandemic influenza on various age groups. METHODS: For the determination of pre-pandemic and post-pandemic seroprevalence, archived plasma samples randomly collected at the clinical biochemistry department of Queen Mary Hospital in the years 2007 and 2010 were used respectively. Microbiologically-confirmed cases and severe cases reported to the Centre for Health Protection (CHP) from May 1, 2009 to May 23, 2010 were included in our analysis. This study was approved by the institutional review board of the Hospital Authority of Hong Kong. RESULTS: 795 and 1000 plasma samples were collected in 2007 and 2010 respectively. In 2007, 8.7% and 14.2% of individuals had HI titers ≥40 and ≥10 respectively. The pre-existing cross-reactive antibodies were mainly found in patients aged >70 years old. In 2010, the overall proportion of individuals with HI titers ≥40 and ≥10 is 23.2% and 42.2%. The highest overall microbiologically-confirmed incidence rate was found in the 0-10 year age group, and decreased with increasing age (ρ=-1.0, p<0.01). A total of 282 severe cases were reported with a mean age was 47.6 years. The incidence rate of severe cases showed an apparent bimodal age distribution, with higher incidence rate in the age group 0-10 and those older than 50 years old, and the highest incidence rate being those between 51 and 60 years old. CONCLUSION: While the young adults were most commonly infected, the clinical consequence is most alarming in children and older adults aged over 50 years. Public policies should continue to target this high risk group.published_or_final_versionThe 49th Annual Meeting of the Infectious Diseases Society of America (IDSA 2011), Boston, MA., 20-23 October 2011

The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis

Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6chigh monocytes. Among cardiac macrophage subtypes, WWP2 dysfunction primarily affects Ly6chigh monocytes via modulating Ccl5, and consequentially macrophage infiltration and activation, which contributes to reduced myofibroblast trans-differentiation. WWP2 interacts with transcription factor IRF7, promoting its non-degradative mono-ubiquitination, nuclear translocation and transcriptional activity, leading to upregulation of Ccl5 at transcriptional level. We identify a pro-fibrogenic macrophage subtype in non-ischemic cardiomyopathy, and demonstrate that WWP2 is a key regulator of IRF7-mediated Ccl5/Ly6chigh monocyte axis in heart fibrosis

Wild type and mutant 2009 pandemic influenza A (H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice

Background: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. Principal Findings: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. Conclusion: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation. © 2010 Chan et al.published_or_final_versio