Emerging infectious diseases among indigenous peoples

Many indigenous peoples are at higher risk for emerging infectious diseases compared to other populations. This conference panel focused on diseases of particular concern to Native Americans (American Indians and Alaska Natives), Australian aboriginal peoples, and the Maori of New Zealand. Important emerging diseases among these groups include respiratory tract infections, infections with antimicrobial-resistant organisms, zoonotic diseases, viral hepatitis, Helicobacter pylori and respiratory syncytial virus infections, diseases caused by Group A and B streptococcus, tuberculosis, and bacteremia and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. Although the populations discussed are diverse, they have many things in common, including a high risk for many emerging infectious diseases, the requirement for culturally appropriate prevention and control strategies, and the need for increased leadership within communities of indigenous peoples

Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2

Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis

13 C-, 15 N- and 31 P-NMR studies of oxidized and reduced low molecular mass thioredoxin reductase and some mutant proteins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65853/1/j.1432-1033.2004.04043.x.pd

Application of Inelastic Neutron Scattering to the Methanol-to-Gasoline Reaction Over a ZSM-5 Catalyst

Inelastic neutron scattering (INS) is used to investigate a ZSM-5 catalyst that has been exposed to methanol vapour at elevated temperature. In-line mass spectrometric analysis of the catalyst exit stream confirms methanol-to-gasoline chemistry, whilst ex situ INS measurements detect hydrocarbon species formed in/on the catalyst during methanol conversion. These preliminary studies demonstrate the capability of INS to complement infrared spectroscopic characterisation of the hydrocarbon pool present in/on ZSM-5 during the MTG reaction

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

Summary High-grade gliomas (HGG) are a devastating group of cancers, representing the leading cause of brain tumor-related death in both children and adults. Therapies aimed at mechanisms intrinsic to the glioma cell have translated to only limited success; effective therapeutic strategies will need to also target elements of the tumor microenvironment that promote glioma progression. We recently demonstrated that neuronal activity robustly promotes the growth of a range of molecularly and clinically distinct HGG types, including adult glioblastoma (GBM), anaplastic oligodendroglioma, pediatric GBM, and diffuse intrinsic pontine glioma (DIPG)1. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway1. However, neuroligin-3 necessity to glioma growth, proteolytic mechanism of secretion and further molecular consequences in glioma remain to be clarified. Here, we demonstrate a striking dependence of HGG growth on microenvironmental neuroligin-3, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy

The Lyman break analogue Haro 11: spatially resolved chemodynamics with VLT FLAMES

Using VLT/Fibre Large Array Multi Element Spectrograph (FLAMES) optical integral field unit observations, we present the first spatially resolved spectroscopic study of the well-known blue compact galaxy Haro 11, thought to be a local analogue to high-redshift Lyman break galaxies. Haro 11 displays complex emission line profiles, consisting of narrow (full width at half-maximum, FWHM ≲ 200 km s-1) and broad (FWHM ∼ 200–300 km s-1) components. We identify three distinct emission knots kinematically connected to one another. A chemodynamical analysis is presented, revealing that spatially resolved ionic and elemental abundances do not agree with those derived from integrated spectra across the galaxy. We conclude that this is almost certainly due to the surface brightness weighting of electron temperature in integrated spectra, leading to higher derived abundances. We find that the eastern knot has a low gas density, but a higher temperature (by ∼4000 K) and consequently an oxygen abundance ∼0.4 dex lower than the neighbouring regions. A region of enhanced N/O is found specifically in Knot C, confirming previous studies that found anomalously high N/O ratios in this system. Maps of the Wolf–Rayet (WR) feature at 4686 Å reveal large WR populations (∼900–1500 stars) in Knots A and B. The lack of WR stars in Knot C combined with an age of ∼7.4 Myr suggests that a recently completed WR phase may be responsible for the observed N/O excess. Conversely, the absence of N-enriched gas and strong WR emission in Knots A and B suggests that we are observing these regions at an epoch where stellar ejecta has yet to cool and mix with the interstellar medium

A VLT VIMOS integral field spectroscopic study of perturbed blue compact galaxies: UM 420 and UM 462

We report on optical integral field spectroscopy of two unrelated blue compact galaxies mapped with the 13 x 13 arcsec^2 VIMOS integral field unit at a resolution of 0.33 x 0.33 arcsec^2. Continuum and background subtracted emission line maps in the light of [O III] 5007, H-alpha, and [N II] 6584 are presented. Both galaxies display signs of ongoing perturbation and/or interaction. UM 420 is resolved for the first time to be a merging system composed of two starbursting components with an 'arm-like' structure associated with the largest component. UM 462 which is a disrupted system of irregular morphology is resolved into at least four starbursting regions. Maps of the H-alpha radial velocity and FWHM are discussed. No underlying broad line region was detected from either galaxy as the emission lines are well-fitted with single Gaussian profiles only. Electron temperatures and densities as well as the abundances of helium, oxygen, nitrogen, and sulphur were computed from spectra integrated over the whole galaxies and for each area of recent star formation. Maps of the O/H ratio are presented: these galaxies show oxygen abundances that are ~20 per cent solar. No evidence of substantial abundance variations across the galaxies that would point to significant nitrogen or oxygen self-enrichment is found (<0.2 dex limit). Contrary to previous observations, this analysis does not support the classification of these BCGs as Wolf-Rayet galaxies as the characteristic broad emission line features have not been detected in our spectra. Baldwin-Phillips-Terlevich emission line ratio diagrams which were constructed on a pixel by pixel basis indicate that the optical spectra of these systems are predominantly excited by stellar photoionization.Comment: 19 pages, 14 figure

Performance measurement for co-occurring mental health and substance use disorders

<p>Abstract</p> <p>Background</p> <p>Co-occurring mental health and substance use disorders (COD) are the norm rather than the exception. It is therefore critical that performance measures are developed to assess the quality of care for individuals with COD irrespective of whether they seek care in mental health systems or substance abuse systems or both.</p> <p>Methods</p> <p>We convened an expert panel and asked them to rate a series of structure, process, and outcomes measures for COD using a structured evaluation tool with domains for importance, usefulness, validity, and practicality.</p> <p>Results</p> <p>We chose twelve measures that demonstrated promise for future pilot testing and refinement. The criteria that we applied to select these measures included: balance across structure, process, and outcome measures, quantitative ratings from the panelists, narrative comments from the panelists, and evidence the measure had been tested in a similar form elsewhere.</p> <p>Conclusion</p> <p>To be successful performance measures need to be developed in such a way that they align with needs of administrators and providers. Policymakers need to work with all stakeholders to establish a concrete agenda for developing, piloting and implementing performance measures that include COD. Future research could begin to consider strategies that increase our ability to use administrative coding in mental health and substance use disorder systems to efficiently capture quality relevant clinical data.</p