Down\u27s syndrome, neroinflammation, and Alzheimer neuropathogenesis

Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21) and is the prevailing cause of mental retardation. In addition to the mental deficiencies and physical anomalies noted at birth, triplication of chromosome 21 gene products results in the neuropathological and cognitive changes of Alzheimer\u27s disease (AD). Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that this chromosome 21 gene product was a principal neuropathogenic culprit in AD as well as DS. The discovery of neuroinflammatory changes, including dramatic proliferation of activated glia overexpressing a chromosome 2 gene product--the pluripotent immune cytokine interleukin-1 (IL-1)--and a chromosome 21 gene product--S100B--in the brains of fetuses, neonates, and children with DS opened the possibility that early events in Alzheimer pathogenesis were driven by cytokines. The specific chromosome 21 gene products and the complexity of the mechanisms they engender that give rise to the neuroinflammatory responses noted in fetal development of the DS brain and their potential as accelerators of Alzheimer neuropathogenesis in DS are topics of this review, particularly as they relate to development and propagation of neuroinflammation, the consequences of which are recognized clinically and neuropathologically as Alzheimer\u27s disease

Partial Transport of a Sand-Gravel Sediment

Grains of a single size within a mixed-size bed are entrained over a range of flows. Within this range some grains exposed on the bed surface are active (entrained at least once over the duration of a transport event), while the remaining surface grains are immobile, a condition we define as partial transport. We demonstrate the existence and domain of partial transport using observations of grain entrainment on time series of bed photographs of flume experiments with a widely sorted sand/gravel mixture. The active proportion of the bed surface increases with bed shear stress τ0. At a given τ0, 90% of the active grains are entrained when the cumulative mass transported exceeds approximately 4 times the active mass on the bed. Mobilization of grains in a size fraction increases from 10% to 90% over a range of τ0 of a factor of 2. The bounds of this range increase with grain size Di so that at a given τ0, sizes over a range of a factor of 4 are in a state of partial transport. Fractional transport rates are independent of Di for fully mobilized fractions and decrease rapidly with Di for partially mobile fractions. Partial transport is associated with substantial transport rates of finer, fully mobile sizes, limits both the rate and size distribution of grain exchange with the bed subsurface, and may be the dominant transport condition in many gravel-bed rivers

Next-generation seismic experiments – II: wide-angle, multi-azimuth, 3-D, full-waveform inversion of sparse field data

3-D full-waveform inversion (FWI) is an advanced seismic imaging technique that has been widely adopted by the oil and gas industry to obtain high-fidelity models of P-wave velocity that lead to improvements in migrated images of the reservoir. Most industrial applications of 3-D FWI model the acoustic wavefield, often account for the kinematic effect of anisotropy, and focus on matching the low-frequency component of the early arriving refractions that are most sensitive to P-wave velocity structure. Here, we have adopted the same approach in an application of 3-D acoustic, anisotropic FWI to an ocean-bottom-seismometer (OBS) field data set acquired across the Endeavour oceanic spreading centre in the northeastern Pacific. Starting models for P-wave velocity and anisotropy were obtained from traveltime tomography; during FWI, velocity is updated whereas anisotropy is kept fixed. We demonstrate that, for the Endeavour field data set, 3-D FWI is able to recover fine-scale velocity structure with a resolution that is 2–4 times better than conventional traveltime tomography. Quality assurance procedures have been employed to monitor each step of the workflow; these are time consuming but critical to the development of a successful inversion strategy. Finally, a suite of checkerboard tests has been performed which shows that the full potential resolution of FWI can be obtained if we acquire a 3-D survey with a slightly denser shot and receiver spacing than is usual for an academic experiment. We anticipate that this exciting development will encourage future seismic investigations of earth science targets that would benefit from the superior resolution offered by 3-D FWI

Lithium Treatment of APPSwDI/NOS2−/− Mice Leads to Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition and Altered Inflammatory Phenotype

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2−/− mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2−/− mice for a period of eight months, followed by water maze testing at 12 months of age, immediately prior to sacrifice. We found that lithium significantly lowered hyperphosphorylated tau levels as measured by Western blot and immunocytochemistry. However, we found no apparent neuroprotection, no effect on spatial memory deficits and an increase in histological amyloid deposition. Aβ levels measured biochemically were unaltered. We also found that lithium significantly altered the neuroinflammatory phenotype of the brain, resulting in enhanced alternative inflammatory response while concurrently lowering the classical inflammatory response. Our data suggest that lithium may be beneficial for the treatment of tauopathies but may not be beneficial for the treatment of Alzheimer's disease

Occupational balance: What tips the scales for new students?

The open question, ‘What prevents you from reaching occupational balance?’, was posed within a questionnaire aimed at exploring the meanings of occupation, health and wellbeing with a cohort of first-year occupational therapy students during their initial few weeks at university. Their written responses to the question about occupational balance were analysed and are discussed in this paper. Not surprisingly, occupational balance appeared to be achieved by only a few and more by chance than design. People, time and money factors were identified as the main impediments to achieving occupational balance, with psychological and emotional pressures being at the forefront. Interestingly, despite these barriers, the overall educational benefit of considering the occupational balance question in this way raised the students’ awareness of its relationship to health and wellbeing. This increased awareness might have longer-term health benefits, both personally and professionally, which would be worthy of further research

Motor neuron disease due to neuropathy target esterase gene mutation: Clinical features of the index families

Recently, we reported that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive motor neuron disease (NTE-MND). We describe clinical, neurophysiologic, and neuroimaging features of affected subjects in the index families. NTE-MND subjects exhibited progressive lower extremity spastic weakness that began in childhood and was later associated with atrophy of distal leg and intrinsic hand muscles. NTE-MND resembles Troyer syndrome, except that short stature, cognitive impairment, and dysmorphic features, which often accompany Troyer syndrome, are not features of NTE-MND. Early onset, symmetry, and slow progression distinguish NTE-MND from typical amyotrophic lateral sclerosis. NTE is implicated in organophosphorus compound–induced delayed neurotoxicity (OPIDN). NTE-MND patients have upper and lower motor neuron deficits that are similar to OPIDN. Motor neuron degeneration in subjects with NTE mutations supports the role of NTE and its biochemical cascade in the molecular pathogenesis of OPIDN and possibly other degenerative neurologic disorders. Muscle Nerve, 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78477/1/21777_ftp.pd

Social inclusion and valued roles : a supportive framework

The aim of this paper is to examine the concepts of social exclusion, social inclusion and their relevance to health, well-being and valued social roles. The article presents a framework, based on Social Role Valorization (SRV), which was developed initially to support and sustain socially valued roles for those who are, or are at risk of, being devalued within our society. The framework incorporates these principles and can be used by health professionals across a range of practice, as a legitimate starting point from which to support the acquisition of socially valued roles which are integral to inclusio