High incidence of plasmids in marine Vibrio species isolated from Mai Po Nature Reserve of Hong Kong

Mai Po Nature Reserve is the largest mangrove ecosystem and the most polluted coastal water body in Hong Kong. Plasmids screening of 100 Vibrio isolates randomly showed 45 % of them contained 1-3 plasmids. These plasmid(s)-bearing isolates could be divided into 12 groups based on their plasmid profiles. Phylogenetic analysis of the partial 16S rRNA gene sequences confirmed that all plasmid(s)-bearing isolates belonged to Vibrio cholerae. Full DNA sequences of the plasmids in Groups I (pVCG1.1 and pVCG1.2), II (pVCG2.1), III (pVCG3.2) and IV (pVCG4.1) have been determined and the results showed that pVCG1.1, pVCG2.1 and pVCG3.2 were almost identical. Plasmids pVCG1.1, pVCG1.2 and pVCG4.1 are comprised of 4,439, 2,357 and 2,163 bp with the overall G+C content of 45.57, 53.54 and 43.09 %, respectively. pVCG1.1 is a novel plasmid, and plasmids pVCG1.2 and pVCG4.1 showed homology of replication initiation proteins to that of the theta type replicons. Attempts to cure the plasmids from their hosts were unsuccessful. These data suggest that plasmids of Vibrio spp. are a significant gene reservoir in the marine ecosystem.published_or_final_versio

In the Shadow of the Transiting Disk: Imaging epsilon Aurigae in Eclipse

Eclipses of the single-line spectroscopic binary star, epsilon Aurigae, provide an opportunity to study the poorly-defined companion. We used the MIRC beam combiner on the CHARA array to create interferometric images during eclipse ingress. Our results demonstrate that the eclipsing body is a dark disk that is opaque and tilted, and therefore exclude alternative models for the system. These data constrain the geometry and masses of the components, providing evidence that the F-star is not a massive supergiant star.Comment: As submitted to Nature. Published in Nature April 8, 2010

Thermal-Error Regime in High-Accuracy Gigahertz Single-Electron Pumping

Single-electron pumps based on semiconductor quantum dots are promising candidates for the emerging quantum standard of electrical current. They can transfer discrete charges with part-per-million (ppm) precision in nanosecond time scales. Here, we employ a metal-oxide-semiconductor silicon quantum dot to experimentally demonstrate high-accuracy gigahertz single-electron pumping in the regime where the number of electrons trapped in the dot is determined by the thermal distribution in the reservoir leads. In a measurement with traceability to primary voltage and resistance standards, the averaged pump current over the quantized plateau, driven by a 1-GHz sinusoidal wave in the absence of a magnetic field, is equal to the ideal value of ef within a measurement uncertainty as low as 0.27 ppm

Phenotypic and functional modulation of porcine monocyte-derived dendritic cells for foot-and-mouth disease virus

Dendritic cells (DCs) play an important role in inducing primary antigen-specific immune responses to viral antigens. In this study, the peripheral blood monocyte-derived (PBMC) were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. After 6 days of culture, immature monocyte-derived dendritic cells (Mo-DCs) were generated. The addition of lipopolysaccharide (LPS) during differentiation of Mo-DCs enhanced their ability to stimulate allogeneic mixed lymphocyte reaction (MLR) and alter their ability to produce cytokines. Then, we investigated the interaction between foot-and-mouth disease virus (FMDV) and porcine Mo-DCs in vitro and confirmed that the immunological phenotype and function of porcine Mo-DCs were modulated during FMDV infection. A down-regulated expression of MHC II and CD1 were observed at 48 h post FMDV infection. In addition, the infected porcine Mo-DCs exhibited ultrastructural morphological changes, FMDV-infected porcine Mo-DCs failed to stimulate T cell proliferation in vitro. Moreover, infection of porcine Mo-DCs in vitro induced the secretion of IFN-γ and the suppressive cytokine IL-10 in porcine Mo-DCs. Results indicated that the down-regulation of MHC II and CD1 molecules and the increased secretion of the IFN-γ and IL-10 cytokines might be the mechanisms that FMDV uses to evade the host immune responses.Key words: Dendritic cells, foot-and-mouth disease virus, MHC II, modulation, cytokines

Decoding expectation and surprise in dementia: the paradigm of music

Making predictions about the world and responding appropriately to unexpected events are essential functions of the healthy brain. In neurodegenerative disorders, such as frontotemporal dementia and Alzheimer's disease, impaired processing of 'surprise' may underpin a diverse array of symptoms, particularly abnormalities of social and emotional behaviour, but is challenging to characterize. Here, we addressed this issue using a novel paradigm: music. We studied 62 patients (24 female; aged 53-88) representing major syndromes of frontotemporal dementia (behavioural variant, semantic variant primary progressive aphasia, non-fluent-agrammatic variant primary progressive aphasia) and typical amnestic Alzheimer's disease, in relation to 33 healthy controls (18 female; aged 54-78). Participants heard famous melodies containing no deviants or one of three types of deviant note-acoustic (white-noise burst), syntactic (key-violating pitch change) or semantic (key-preserving pitch change). Using a regression model that took elementary perceptual, executive and musical competence into account, we assessed accuracy detecting melodic deviants and simultaneously recorded pupillary responses and related these to deviant surprise value (information-content) and carrier melody predictability (entropy), calculated using an unsupervised machine learning model of music. Neuroanatomical associations of deviant detection accuracy and coupling of detection to deviant surprise value were assessed using voxel-based morphometry of patients' brain MRI. Whereas Alzheimer's disease was associated with normal deviant detection accuracy, behavioural and semantic variant frontotemporal dementia syndromes were associated with strikingly similar profiles of impaired syntactic and semantic deviant detection accuracy and impaired behavioural and autonomic sensitivity to deviant information-content (all P < 0.05). On the other hand, non-fluent-agrammatic primary progressive aphasia was associated with generalized impairment of deviant discriminability (P < 0.05) due to excessive false-alarms, despite retained behavioural and autonomic sensitivity to deviant information-content and melody predictability. Across the patient cohort, grey matter correlates of acoustic deviant detection accuracy were identified in precuneus, mid and mesial temporal regions; correlates of syntactic deviant detection accuracy and information-content processing, in inferior frontal and anterior temporal cortices, putamen and nucleus accumbens; and a common correlate of musical salience coding in supplementary motor area (all P < 0.05, corrected for multiple comparisons in pre-specified regions of interest). Our findings suggest that major dementias have distinct profiles of sensory 'surprise' processing, as instantiated in music. Music may be a useful and informative paradigm for probing the predictive decoding of complex sensory environments in neurodegenerative proteinopathies, with implications for understanding and measuring the core pathophysiology of these diseases

Sex and age differences in the Multiple Sclerosis prodrome

Background and objectives: Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome. Methods: This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event (“administrative cohort;” n = 6,863) or MS symptom onset (“clinical cohort;” n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30–49, ≥50 years). Results: In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30–49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30–49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30–49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30–49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30–49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05). Discussion: Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation

Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients

<p>Abstract</p> <p>Background</p> <p>Glutathione S-transferases (GSTs) play an important role in metabolizing anti-epileptic drugs (AEDs) in liver. Expressions of GSTs in brain, which may result in poor efficacy of AEDs, have not been well studied. Using clinical cortex specimen from 32 intractable epileptic subjects and 8 non-epileptic controls, the present study investigated the correlation between GSTs and intractable epilepsy.</p> <p>Results</p> <p>Three different GST isoforms (α, μ, and π) were detected with immunohistochemistry. GST-α expression was not seen in any cortex specimens. Sixty three percent (63%) of control and 53% of intractible epileptic specimens showed GST-μ immunoreactivity. No significant difference in intensity of GST-μ staining was observed between these two groups. GST-π expression was found in endothelial cells and glial cells/astrocytes. Fifty percent (50%) of the control patients and 66% of the epileptic patients were GST-π positive. The grading of epileptic patients was significantly higher than that of control patients (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>High levels of GST-π in endothelial cells and glial cells/astrocyte correlate to medical intractable epilepsy, suggesting that GST-π contributes to resistance to AED treatment.</p

Characteristics of a population-based multiple sclerosis cohort treated with disease-modifying drugs in a universal healthcare setting

BACKGROUND: Relatively little is known about the use of disease-modifying drugs (DMDs) for multiple sclerosis (MS) in the population-based universal healthcare setting. This study aimed to describe the characteristics of a population-based cohort with MS and their DMD exposure in four Canadian provinces. METHODS: We identified all adults (aged ≥18 years) with MS using linked population-based health administrative data. Individuals were followed from the most recent of their first MS or demyelinating event or 1 January 1996(study entry), to the earliest of death, emigration, or 31 March 2018(study end). Cohort characteristics examined included sex, age, socioeconomic status, and comorbidity burden. RESULTS: Overall, 10,418/35,894 (29%) of MS cases filled a DMD prescription during the 22-year study period. Most were women (n = 7,683/10,418;74%), and 17% (n = 1,745/10,418) had some comorbidity (Charlson Comorbidity Index≥1) at study entry. Nearly 20% (n = 1,745/10,418) were aged ≥50 when filling their first DMD; the mean age was 39.6 years. CONCLUSIONS: Almost 1 in 6 people with MS had at least some comorbidity, and nearly 1 in 6 were ≥50 years old at the time of their first DMD. As these individuals are typically excluded from clinical trials, findings illustrate the need to understand the harms and benefits of DMD use in these understudied groups