852 research outputs found
Decay times of transitionally dense specularly reflecting meteor trails and potential chemical impact on trail lifetimes
Studies of transitionally dense meteor trails using radars which employ specularly reflecting interferometric techniques are used to show that measurable high-temperature chemistry exists at timescales of a few tenths of a second after the formation of these trails. This is a process which is distinct from the ambient-temperature chemistry that is already known to exist at timescales of tens of seconds and longer in long-lived trails. As a consequence, these transitionally dense trails have smaller lifetimes than might be expected if diffusion were the only mechanism for reducing the mean trail electron density. The process has been studied with four SKiYMET radars at latitudes varying from 10 to 75° N, over a period of more than 10 years, 24 h per day. In this paper we present the best parameters to use to represent this behaviour and demonstrate the characteristics of the temporal and latitudinal variability in these parameters. The seasonal, day-night and latitudinal variations correlate reasonably closely with the corresponding variations of ozone in the upper mesosphere. Possible reasons for these effects are discussed, but further investigations of any causative relation are still the subject of ongoing studies
Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer
ADN tumoral circulant; Medicina de precisiĂł; CĂ ncer de prĂČstataADN tumoral circulante; Medicina de precisiĂłn; CĂĄncer de prĂłstataCirculating tumor DNA; Precision medicine; Prostate cancerContext
Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative.
Objective
To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine.
Evidence acquisition
A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC.
Evidence synthesis
Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers).
Conclusions
Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation
Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.
In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles
New Insights into the Lake Chad Basin Population Structure Revealed by High-Throughput Genotyping of Mitochondrial DNA Coding SNPs
BACKGROUND: Located in the Sudan belt, the Chad Basin forms a remarkable ecosystem, where several unique agricultural and pastoral techniques have been developed. Both from an archaeological and a genetic point of view, this region has been interpreted to be the center of a bidirectional corridor connecting West and East Africa, as well as a meeting point for populations coming from North Africa through the Saharan desert. METHODOLOGY/PRINCIPAL FINDINGS: Samples from twelve ethnic groups from the Chad Basin (nâ=â542) have been high-throughput genotyped for 230 coding region mitochondrial DNA (mtDNA) Single Nucleotide Polymorphisms (mtSNPs) using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. This set of mtSNPs allowed for much better phylogenetic resolution than previous studies of this geographic region, enabling new insights into its population history. Notable haplogroup (hg) heterogeneity has been observed in the Chad Basin mirroring the different demographic histories of these ethnic groups. As estimated using a Bayesian framework, nomadic populations showed negative growth which was not always correlated to their estimated effective population sizes. Nomads also showed lower diversity values than sedentary groups. CONCLUSIONS/SIGNIFICANCE: Compared to sedentary population, nomads showed signals of stronger genetic drift occurring in their ancestral populations. These populations, however, retained more haplotype diversity in their hypervariable segments I (HVS-I), but not their mtSNPs, suggesting a more ancestral ethnogenesis. Whereas the nomadic population showed a higher Mediterranean influence signaled mainly by sub-lineages of M1, R0, U6, and U5, the other populations showed a more consistent sub-Saharan pattern. Although lifestyle may have an influence on diversity patterns and hg composition, analysis of molecular variance has not identified these differences. The present study indicates that analysis of mtSNPs at high resolution could be a fast and extensive approach for screening variation in population studies where labor-intensive techniques such as entire genome sequencing remain unfeasible
Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar
More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself
Selecting cash management models from a multiobjective perspective
[EN] This paper addresses the problem of selecting cash management models under different operating conditions from a multiobjective perspective considering not only cost but also risk. A number of models have been proposed to optimize corporate cash management policies. The impact on model performance of different operating conditions becomes an important issue. Here, we provide a range of visual and quantitative tools imported from Receiver Operating Characteristic (ROC) analysis. More precisely, we show the utility of ROC analysis from a triple perspective as a tool for: (1) showing model performance; (2) choosingmodels; and (3) assessing the impact of operating conditions on model performance. We illustrate the selection of cash management models by means of a numerical example.Work partially funded by projects Collectiveware TIN2015-66863-C2-1-R (MINECO/FEDER) and 2014 SGR 118.Salas-Molina, F.; RodrĂguez-Aguilar, JA.; DĂaz-GarcĂa, P. (2018). 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Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use
Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the worldâs most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1â2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian PerĂč
Self-Organization of Anastral Spindles by Synergy of Dynamic Instability, Autocatalytic Microtubule Production, and a Spatial Signaling Gradient
Assembly of the mitotic spindle is a classic example of macromolecular self-organization. During spindle assembly, microtubules (MTs) accumulate around chromatin. In centrosomal spindles, centrosomes at the spindle poles are the dominating source of MT production. However, many systems assemble anastral spindles, i.e., spindles without centrosomes at the poles. How anastral spindles produce and maintain a high concentration of MTs in the absence of centrosome-catalyzed MT production is unknown. With a combined biochemistry-computer simulation approach, we show that the concerted activity of three components can efficiently concentrate microtubules (MTs) at chromatin: (1) an external stimulus in form of a RanGTP gradient centered on chromatin, (2) a feed-back loop where MTs induce production of new MTs, and (3) continuous re-organization of MT structures by dynamic instability. The mechanism proposed here can generate and maintain a dissipative MT super-structure within a RanGTP gradient
Reward devaluation disrupts latent inhibition in fear conditioning
Three experiments explored the link between
reward shifts and latent inhibition (LI). Using consummatory
procedures, rewards were either downshifted
from 32% to 4% sucrose (Experiments 1â2), or
upshifted from 4% to 32% sucrose (Experiment 3). In
both cases, appropriate unshifted controls were also included.
LI was implemented in terms of fear conditioning
involving a single tone-shock pairing after extensive
tone-only preexposure. Nonpreexposed controls were also
included. Experiment 1 demonstrated a typical LI effect
(i.e., disruption of fear conditioning after preexposure to the
tone) in animals previously exposed only to 4% sucrose.
However, the LI effect was eliminated by preexposure to a
32%-to-4% sucrose devaluation. Experiment 2 replicated
this effect when the LI protocol was administered immediately
after the reward devaluation event. However, LI was
restored when preexposure was administered after a 60-
min retention interval. Finally, Experiment 3 showed that
a reward upshift did not affect LI. These results point to a
significant role of negative emotion related to reward devaluation
in the enhancement of stimulus processing despite
extensive nonreinforced preexposure experience
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