Antibody-binding epitope differences in the nucleoprotein of avian and mammalian influenza A viruses

Abstract Influenza virus nucleoprotein (NP) binds to the viral genome RNA and forms the internal ribonucleoprotein complex of the virus particle. Avian and human influenza virus NP have characteristic differences at several amino acid positions. It is not known whether any of these differences can be recognized by antibodies. In the present study five monoclonal antibodies (MAbs) were produced against NP of A/Duck/Novosibirsk/56/05 (H5N1) influenza virus. Two MAbs discerned human and avian influenza strains on ELISA testing. The NP expressed in a prokaryotic system was used for the analysis of site-specific mutants carrying amino acid substitutions in the relevant positions. Amino acid residues in positions 100 and 101 were shown to be recognized by the MAbs. The residue in position 100 is host-specific, and its recognition by the MAb 2E6 may be useful for the differentiation of human and avian viruses. The data are discussed in view of the effects of amino acid substitutions in influenza virus NP affecting both host range and antibody-binding specificity.     

Multidisciplinary design and implementation of a day program specialized for the frontotemporal dementias

To supervise activities for patients with frontotemporal dementias presents major challenges to day programs typically equipped to care for more elderly, frail patients. In this article, we present the development and immediate outcomes of integrating a day program specialized for patients with frontal lobe disturbances into an already established day program. Planning required new collaborations between the ambulatory memory clinic and the day program staff. Immediate outcomes have included relief of burden for an under-served group of caregivers and behavioral management that more seamlessly combines strategies for medication titration, environmental adjustments, and activity participation.     

Sonochemically prepared BSA microspheres containing Gemcitabine,and their potential application in renal cancer therapeutics

This report demonstrates the formation and characterization of sonochemically prepared bovine serum albumin (BSA)–Gemzar (Gemcitabine) microspheres and shows their increased anticancer activity compared to pristine Gemzar. The amount of loaded Gemzar was determined by light absorption measurements. The BSA–Gemzar composite was analyzed and characterized by optical microscopy and scanning electron microscopy. The release kinetics of Gemzar from the proteinaceous microspheres was tested. The BSA–Gemzar composite was examined for its anticancer activity (in vitro) in renal cancer cells (RCC, 786-O cells) using [³H]thymidine incorporation assays. It was found that the influence of the Gemzar-loaded microspheres on the cancer cells was significantly greater than that of an equimolar concentration of pristine Gemzar.     

Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled‐up primate brain

The human brain is often considered to be the most cognitively capable among mammalian brains and to be much larger than expected for a mammal of our body size. Although the number of neurons is generally assumed to be a determinant of computational power, and despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human‐sized primate. We find that the adult male human brain contains on average 86.1 ± 8.1 billion NeuN‐positive cells (“neurons”) and 84.6 ± 9.8 billion NeuN‐negative (“nonneuronal”) cells. With only 19% of all neurons located in the cerebral cortex, greater cortical size (representing 82% of total brain mass) in humans compared with other primates does not reflect an increased relative number of cortical neurons. The ratios between glial cells and neurons in the human brain structures are similar to those found in other primates, and their numbers of cells match those expected for a primate of human proportions. These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled‐up primate brain. J. Comp. Neurol. 513:532–541, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence and age-of-onset distributions of DSM IV mental disorders and their severity among school going Omani adolescents and youths: WMH-CIDI findings

Background  

There is a dearth of studies exploring the magnitude of mental disorders amongst adolescents and youths in the Arab world. To our knowledge, this phase 2 survey in Oman is the first nationally representative school-based study to determine the prevalence of DSM-IV mental disorders (lifetime and over the preceding 12 months), their age-of-onset distributions and determine their severity over the past 12 months using the World Mental Health-Composite International Diagnostic Interview, the WMH-CIDI, used for international comparison.     

Health services utilization by school going Omani adolescents and youths with DSM IV mental disorders and barriers to service use

Background  

Recent corpus of research suggests that psychiatric disorders amongst adolescents and youths are an emerging global challenge, but there is paucity of studies exploring health services utilization by this age group in Arab region.     

Large-scale simulation of the human arterial tree

1. Full-scale simulations of the virtual physiological human (VPH) will require significant advances in modelling, multiscale mathematics, scientific computing and further advances in medical imaging. Herein, we review some of the main issues that need to be resolved in order to make three-dimensional (3D) simulations of blood flow in the human arterial tree feasible in the near future. 2. A straightforward approach is computationally prohibitive even on the emerging petaflop supercomputers, so a three-level hierarchical approach based on vessel size is required, consisting of: (i) a macrovascular network (MaN); (ii) a mesovascular network (MeN); and (iii) a microvascular network (MiN). We present recent simulations of MaN obtained by solving the 3D Navier-Stokes equations on arterial networks with tens of arteries and bifurcations and accounting for the neglected dynamics through proper boundary conditions. 3. A multiscale simulation coupling MaN-MeN-MiN and running on hundreds of thousands of processors on petaflop computers will require no more than a few CPU hours per cardiac cycle within the next 5 years. The rapidly growing capacity of supercomputing centres opens up the possibility of simulation studies of cardiovascular diseases, drug delivery, perfusion in the brain and other pathologies.     

Author Correction: Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors

Investigational New Drugs -     

Multidrug resistance protein 4 protects bone marrow, thymus, spleen, and intestine from nucleotide analogue-induced damage

Nucleoside-based analogues are mainstays in the treatment of cancer, viral infections, and inflammatory diseases. Recent studies showing that the ATP-binding cassette transporter, multidrug resistance protein 4, is able to efflux nucleoside and nucleotide analogues from transfected cells suggests that the pump may affect the efficacy of this class of agents. However, the in vivo pharmacologic functions of the pump are largely unexplored. Here, using Mrp4(-/-) mice as a model system, and the nucleotide analogue, 9'-(2'-phosphonylmethoxyethyl)-adenine (PMEA) as a probe, we investigate the ability of Mrp4 to function in vivo as an endogenous resistance factor. In the absence of alterations in plasma PMEA levels, Mrp4-null mice treated with PMEA exhibit increased lethality associated with marked toxicity in several tissues. Affected tissues include the bone marrow, spleen, thymus, and gastrointestinal tract. In addition, PMEA penetration into the brain is increased in Mrp4(-/-) mice. These findings indicate that Mrp4 is an endogenous resistance factor, and that the pump may be a component of the blood-brain barrier for nucleoside-based analogues. This is the first demonstration that an ATP-binding cassette transporter can affect in vivo tissue sensitivity towards this class of agents.