To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD).
The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian ...family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis.
A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb.
A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
The most common form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn Superoxide ...dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.
Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI may be a useful biomarker for bleeding-prone small vessel diseases, with potential relevance for diagnosis, prognosis (especially ...for antithrombotic-related bleeding risk), and understanding mechanisms of symptoms, including cognitive impairment. To address these questions, it is necessary to reliably measure their presence and distribution in the brain. We designed and systematically validated the Microbleed Anatomical Rating Scale (MARS). We measured intrarater and interrater agreement for presence, number, and anatomical distribution of microbleeds using MARS across different MRI sequences and levels of observer experience.
We studied a population of 301 unselected consecutive patients admitted to our stroke unit using 2 GRE T2*-weighted MRI sequences (echo time TE 40 and 26 ms). Two independent raters with different MRI rating expertise identified, counted, and anatomically categorized microbleeds.
At TE = 40 ms, agreement for microbleed presence in any brain location was good to very good (intrarater kappa = 0.85 95% confidence interval (CI) 0.77-0.93; interrater kappa = 0.68 95% CI 0.58-0.78). Good to very good agreement was reached for the presence of microbleeds in each anatomical region and in individual cerebral lobes. Intrarater and interrater reliability for the number of microbleeds was excellent (intraclass correlation coefficient ICC = 0.98 95% CI 0.97-0.99 and ICC = 0.93 0.91-0.94). Very good interrater reliability was obtained at TE = 26 ms (kappa = 0.87 95% CI 0.61-1) for definite microbleeds in any location.
The Microbleed Anatomical Rating Scale has good intrarater and interrater reliability for the presence of definite microbleeds in all brain locations when applied to different MRI sequences and levels of observer experience.
Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in ...sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.
HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the ...brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.
The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.
The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.
The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and ...cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.
The generation of pancreatic cell types from renewable cell sources holds promise for cell replacement therapies for diabetes. Although most effort has focused on generating pancreatic beta cells, ...considerable evidence indicates that glucagon secreting alpha cells are critically involved in disease progression and proper glucose control. Here we report on the generation of stem cell-derived human pancreatic alpha (SC-alpha) cells from pluripotent stem cells via a transient pre-alpha cell intermediate. These pre-alpha cells exhibit a transcriptional profile similar to mature alpha cells and although they produce proinsulin protein, they do not secrete significant amounts of processed insulin. Compound screening identified a protein kinase c activator that promotes maturation of pre-alpha cells into SC-alpha cells. The resulting SC-alpha cells do not express insulin, share an ultrastructure similar to cadaveric alpha cells, express and secrete glucagon in response to glucose and some glucagon secretagogues, and elevate blood glucose upon transplantation in mice.
Background
The degradation of forests in developing countries, particularly those within tropical and subtropical latitudes, is perceived to be an important contributor to global greenhouse gas ...emissions. However, the impacts of forest degradation are understudied and poorly understood, largely because international emission reduction programs have focused on deforestation, which is easier to detect and thus more readily monitored. To better understand and seize opportunities for addressing climate change it will be essential to improve knowledge of greenhouse gas emissions from forest degradation.
Results
Here we provide a consistent estimation of forest degradation emissions between 2005 and 2010 across 74 developing countries covering 2.2 billion hectares of forests. We estimated annual emissions of 2.1 billion tons of carbon dioxide, of which 53% were derived from timber harvest, 30% from woodfuel harvest and 17% from forest fire. These percentages differed by region: timber harvest was as high as 69% in South and Central America and just 31% in Africa; woodfuel harvest was 35% in Asia, and just 10% in South and Central America; and fire ranged from 33% in Africa to only 5% in Asia. Of the total emissions from deforestation and forest degradation, forest degradation accounted for 25%. In 28 of the 74 countries, emissions from forest degradation exceeded those from deforestation.
Conclusions
The results of this study clearly demonstrate the importance of accounting greenhouse gases from forest degradation by human activities. The scale of emissions presented indicates that the exclusion of forest degradation from national and international GHG accounting is distorting. This work helps identify where emissions are likely significant, but policy developments are needed to guide when and how accounting should be undertaken. Furthermore, ongoing research is needed to create and enhance cost-effective accounting approaches.
Galaxy And Mass Assembly (GAMA): stellar mass estimates Taylor, Edward N.; Hopkins, Andrew M.; Baldry, Ivan K. ...
Monthly notices of the Royal Astronomical Society,
December 2011, Letnik:
418, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper describes the first catalogue of photometrically derived stellar mass estimates for intermediate-redshift (z < 0.65; median z= 0.2) galaxies in the Galaxy And Mass Assembly (GAMA) ...spectroscopic redshift survey. These masses, as well as the full set of ancillary stellar population parameters, will be made public as part of GAMA data release 2. Although the GAMA database does include near-infrared (NIR) photometry, we show that the quality of our stellar population synthesis fits is significantly poorer when these NIR data are included. Further, for a large fraction of galaxies, the stellar population parameters inferred from the optical-plus-NIR photometry are formally inconsistent with those inferred from the optical data alone. This may indicate problems in our stellar population library, or NIR data issues, or both; these issues will be addressed for future versions of the catalogue. For now, we have chosen to base our stellar mass estimates on optical photometry only. In light of our decision to ignore the available NIR data, we examine how well stellar mass can be constrained based on optical data alone. We use generic properties of stellar population synthesis models to demonstrate that restframe colour alone is in principle a very good estimator of stellar mass-to-light ratio, M
*/Li
. Further, we use the observed relation between restframe (g−i) and M
*/Li
for real GAMA galaxies to argue that, modulo uncertainties in the stellar evolution models themselves, (g−i) colour can in practice be used to estimate M
*/Li
to an accuracy of ≲0.1 dex (1σ). This 'empirically calibrated' (g−i)-M
*/Li
relation offers a simple and transparent means for estimating galaxies' stellar masses based on minimal data, and so provides a solid basis for other surveys to compare their results to z≲0.4 measurements from GAMA.
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