85 research outputs found
Modeling oscillatory Microtubule--Polymerization
Polymerization of microtubules is ubiquitous in biological cells and under
certain conditions it becomes oscillatory in time. Here simple reaction models
are analyzed that capture such oscillations as well as the length distribution
of microtubules. We assume reaction conditions that are stationary over many
oscillation periods, and it is a Hopf bifurcation that leads to a persistent
oscillatory microtubule polymerization in these models. Analytical expressions
are derived for the threshold of the bifurcation and the oscillation frequency
in terms of reaction rates as well as typical trends of their parameter
dependence are presented. Both, a catastrophe rate that depends on the density
of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay
reaction, such as the depolymerization of shrinking microtubules or the decay
of oligomers, support oscillations. For a tubulin dimer concentration below the
threshold oscillatory microtubule polymerization occurs transiently on the
route to a stationary state, as shown by numerical solutions of the model
equations. Close to threshold a so--called amplitude equation is derived and it
is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Rare genetic variants explain missing heritability in smoking
Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability (hSNP2) was estimated from 0.13 to 0.28 (s.e., 0.10–0.13) in European ancestries, with 35–74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5–4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability (hped2, 0.18–0.34). In the African ancestry samples, hSNP2 was estimated from 0.03 to 0.33 (s.e., 0.09–0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking
Identificando sitios candidatos para implementar la estrategia de cultivos biofortificados en Latinoamérica y el Caribe
Avances en la identificación de sitios candidatos para implementar la estrategia de cultivos biofortificados en Latinoamérica y el Caribe
Development implementation and evaluation of a methodology to identify populations at risk for nutritional deficiency
Combination of Antitachycardia Pacemaker and Automatic Implantable Cardioverter/Defibrillator for Ventricular Tachycardia
Zoeal morphology of Pachygrapsus transversus (Gibbes) (Decapoda, Grapsidae) reared in the laboratory
Ovigerous females of Pachygrapsus transversus (Gibbes, 1850) were collected on the Praia Dura and Saco da Ribeira beaches, Ubatuba, São Paulo, Brazil. Larvae were individually reared in a climatic room at 25ºC temperature, salinities of 28, 32 and 35‰ and under natural photoperiod conditions. The best rearing results were observed at 35%o salinity. Seven zoeal instars were observed, drawing and described in detail. The data are compared with those obtained for P. gracilis (Saussure, 1858)
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