Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips

The Brassica napus 60K Illumina Infinium™ SNP array has had huge international uptake in the rapeseed community due to the revolutionary speed of acquisition and ease of analysis of this high-throughput genotyping data, particularly when coupled with the newly available reference genome sequence. However, further utilization of this valuable resource can be optimized by better understanding the promises and pitfalls of SNP arrays. We outline how best to analyze Brassica SNP marker array data for diverse applications, including linkage and association mapping, genetic diversity and genomic introgression studies. We present data on which SNPs are locus-specific in winter, semi-winter and spring B. napus germplasm pools, rather than amplifying both an A-genome and a C-genome locus or multiple loci. Common issues that arise when analyzing array data will be discussed, particularly those unique to SNP markers and how to deal with these for practical applications in Brassica breeding applications

A new era in the treatment of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system with a multifactorial aetiology and highly variable natural history. A growing understanding of the immunopathogenesis of the condition has led to an expanding array of therapies for this previously untreatable disease. While a cure for MS remains elusive, the potential to reduce inflammatory disease activity by preventing relapses and minimising disease progression is achievable. The importance of early treatment in minimising long-term disability is increasingly recognised. Most of the newer, more effective therapies are associated with risks and practical problems that necessitate an active management strategy and continuous vigilance. While the initiation of these therapies is likely to remain the responsibility of neurologists, other specialist physicians and general practitioners will be involved in the identification and management of adverse effects

Biology of larks (Aves: Alaudidae) in the central Namib Desert

1. The biology of six species of larks in the Namib Desert near Walvis Bay, South West Africa, was studied in 1964, 1965 and 1966.2. All species reproduced following rainfall in summer and autumn months, with the appearance of green grass and abundant insects on which the birds fed.3. The primarily insectivorous species, Certhilauda albofasciata, shows no seasonality in moulting and testicular development, and reproduces whenever local rainfall results in favourable feeding and nesting circumstances, while the primarily granivorous Spizoeorys starki and Eremopterix verticalis have markedly seasonal testicular and moulting cycles timed so that reproduction occurs only during the late summer and autumn months. Ammomanes grayi is intermediate in food habits and in timing of moulting and reproduction, and C. albescens and Mirafra naevia may also be intermediate in this respect.4. S. starki and E. verticalis are the only larks that normally drink, but flocks of both species were observed that were independent of drinking water.5. Larks avoid heat stress during daytime by keeping to the shade of stones, tufts of vegetation and mouths of rodent burrows; and nests are nearly always placed on the shady side of a stone' or tuft of grass.6. It is suggested that larks may be successful desert occupants because they have not become highly specialized and therefore can tolerate rapidly and severely changing environ-mental conditions associated with drought and irregular rainfal

Metabolism of inorganic cations by quail (Coturnix Coturnix) drinking solutions of CaCl2 and MgCl2

1. 1. In experiments to indicate the abilities of birds to tolerate and excrete Mg and Ca in drinking water, twenty-eight male quail received solutions of CaCl2 or MgCl2 perenterally for several days or in single doses. The concentrations of Ca, Mg, Na and K were subsequently measured in excretory fluids voided spontaneously or collected by intubating cloaca and rectum, and in plasma.2. 2. The physiological mechanisms of quail which deal with divalent cations are affected similarly by both Ca and Mg, without distinguishing sharply between the two.3. 3. Calcium appears to be less readily absorbed in the gut than Mg.4. 4. Excretion of Na is increased by intake of CaCl2 or MgCl2.5. 5. Water appears to be absorbed from ureteral urine in cloaca or rectum.6. 6. The effects of CaCl2 and MgCl2 on salt metabolism of the quail are complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33699/1/0000211.pd

Regarding the publication The Multiple Sclerosis Severity Score: Fluctuations and prognostic ability in a longitudinal cohort of patients with MS authored by RH Gross et al.

We agree with the authors that the MSSS was devised as a descriptor of disease severity for groups of patients and was intended to be used for statistical comparisons between such groups, and thence also to be useful for stratification in clinical trials or just as a population disease severity descriptor. Other researchers have made claims for it as a prognostic measure for individuals

Regarding the publication The Multiple Sclerosis Severity Score: Fluctuations and prognostic ability in a longitudinal cohort of patients with MS authored by RH Gross <i>et al</i>.

We agree with the authors that the MSSS was devised as a descriptor of disease severity for groups of patients and was intended to be used for statistical comparisons between such groups, and thence also to be useful for stratification in clinical trials or just as a population disease severity descriptor. Other researchers have made claims for it as a prognostic measure for individuals

Multiple Sclerosis

Multiple sclerosis (MS) is a complex disorder of the central nervous system (CNS) in which scattered patches of inflammation occur repeatedly over the course of years in the brain and spinal cord, producing damage of variable severity to major motor and sensory pathways. It is the most common disability-producing disease of the CNS in young adults in Europe and North America. The cause is unknown, and the clinical presentation and course are highly variable. This chapter gives an overview of the pathology, epidemiology, effects, assessment, and management of this disease. We conclude by outlining some issues concerning MS, the resolution of which would improve assessment and treatment practices

NACA Research Memorandums

Report presenting an analysis of an investigation of a simple altitude control based on static-pressure and rate-of-climb sensing is combined with a supersonic missile as a servomechanism to yield the closed-loop behavior of the entire system. The control system was found to function successfully at a low-altitude missile of the boost-guide type and would likely perform well at high altitude