2,857 research outputs found
Generalized Species Sampling Priors with Latent Beta reinforcements
Many popular Bayesian nonparametric priors can be characterized in terms of
exchangeable species sampling sequences. However, in some applications,
exchangeability may not be appropriate. We introduce a {novel and
probabilistically coherent family of non-exchangeable species sampling
sequences characterized by a tractable predictive probability function with
weights driven by a sequence of independent Beta random variables. We compare
their theoretical clustering properties with those of the Dirichlet Process and
the two parameters Poisson-Dirichlet process. The proposed construction
provides a complete characterization of the joint process, differently from
existing work. We then propose the use of such process as prior distribution in
a hierarchical Bayes modeling framework, and we describe a Markov Chain Monte
Carlo sampler for posterior inference. We evaluate the performance of the prior
and the robustness of the resulting inference in a simulation study, providing
a comparison with popular Dirichlet Processes mixtures and Hidden Markov
Models. Finally, we develop an application to the detection of chromosomal
aberrations in breast cancer by leveraging array CGH data.Comment: For correspondence purposes, Edoardo M. Airoldi's email is
[email protected]; Federico Bassetti's email is
[email protected]; Michele Guindani's email is
[email protected] ; Fabrizo Leisen's email is
[email protected]. To appear in the Journal of the American
Statistical Associatio
STAR FORMATION HISTORY OF THE SMALL MAGELLANIC CLOUD: SIX HUBBLE SPACE TELESCOPE/ADVANCED CAMERA FOR SURVEY FIELDS
We observed six fields of the Small Magellanic Cloud (SMC) with the Advanced Camera for Survey on board the Hubble Space Telescope in the F555W and F814W filters. These fields sample regions characterized by very different star and gas densities, and, possibly, by different evolutionary histories. We find that the SMC was already forming stars similar to 12 Gyr ago, even if the lack of a clear horizontal branch suggests that in the first few billion years the star formation activity was low. Within the uncertainties of our two-band photometry, we find evidence of a radial variation in chemical enrichment, with the SMC outskirts characterized by lower metallicity than the central zones. From our color-magnitude diagrams, we also infer that the SMC formed stars over a long interval of time until similar to 2-3 Gyr ago. After a period of modest activity, star formation increased again in the recent past, especially in the bar and the wing of the SMC, where we see an enhancement in the star-formation activity starting from similar to 500 Myr ago. The inhomogeneous distribution of stars younger than similar to 100 Myr indicates that recent star formation has mainly developed locally
Structural basis of synaptic vesicle assembly promoted by α-synuclein.
α-synuclein (αS) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson's disease. Although the specific function of αS is still unclear, a general consensus is forming that it has a key role in regulating the process of neurotransmitter release, which is associated with the mediation of synaptic vesicle interactions and assembly. Here we report the analysis of wild-type αS and two mutational variants linked to familial Parkinson's disease to describe the structural basis of a molecular mechanism enabling αS to induce the clustering of synaptic vesicles. We provide support for this 'double-anchor' mechanism by rationally designing and experimentally testing a further mutational variant of αS engineered to promote stronger interactions between synaptic vesicles. Our results characterize the nature of the active conformations of αS that mediate the clustering of synaptic vesicles, and indicate their relevance in both functional and pathological contexts
Is the association between precarious employment and mental health mediated by economic difficulties in males? Results from two Italian studies
Flexible employment is increasing across Europe and recent studies show an association with poor mental health. The goal of the current study is to examine this association in the Italian population to assess the possible mediating role of financial strain. Methods: Data were obtained by two Italian cross-sectional studies (PASSI and HIS) aimed at monitoring the general population health status, health behaviours and determinants. Mental health status was assessed using alternatively two validated questionnaires (the PHQ-2 and the MCS-12 score) and Poisson regression models were performed to assess if precarious work was associated with poor mental health. A formal mediation analysis was conducted to evaluate if the association between precarious work and mental health was mediated by financial strain. Results: The analyses were performed on 31,948 subjects in PASSI and on 21,894 subjects in HIS. A nearly two-fold risk of depression and poor mental health was found among precarious workers, compared to workers with a permanent contract, which was strongly mediated by financial strain. Conclusions: Even with the limitations of a cross-sectional design, this research supports that precarious employment contributes through financial strain to reduce the mental health related quality of life and to increase mental disorders such as symptoms of depression or dysthymia. This suggests that when stability in work cannot be guaranteed, it would be appropriate to intervene on the wages of precarious jobs and to provide social safety nets for ensuring adequate income
Proboscis Morphology and Its Relationship to Feeding Habits in Noctuid Moths
This study describes proboscis morphology and identifies morphometric differences among five species of noctuid moths with different feeding habits (fruit versus nectar-feeding). Morphological and morphometric parameters were analyzed using scanning electron microscopy and light microscopy. Measurements included: galea height in ten sites from base to tip, total proboscis length, and length of the distal region that contains large sensilla styloconica and / or tearing hooks and erectible barbs. Both morphometric and morphological differences were identified among species within and between feeding guilds, and these results are discussed in light of the feeding habits of each species
The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study
Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity
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Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies
The N-Terminal Domain of ERK1 Accounts for the Functional Differences with ERK2
The Extracellular Regulated Kinase 1 and 2 transduce a variety of extracellular stimuli regulating processes as diverse as proliferation, differentiation and synaptic plasticity. Once activated in the cytoplasm, ERK1 and ERK2 translocate into the nucleus and interact with nuclear substrates to induce specific programs of gene expression. ERK1/2 share 85% of aminoacid identity and all known functional domains and thence they have been considered functionally equivalent until recent studies found that the ablation of either ERK1 or ERK2 causes dramatically different phenotypes. To search a molecular justification of this dichotomy we investigated whether the different functions of ERK1 and 2 might depend on the properties of their cytoplasmic-nuclear trafficking. Since in the nucleus ERK1/2 is predominantly inactivated, the maintenance of a constant level of nuclear activity requires continuous shuttling of activated protein from the cytoplasm. For this reason, different nuclear-cytoplasmic trafficking of ERK1 and 2 would cause a differential signalling capability. We have characterised the trafficking of fluorescently tagged ERK1 and ERK2 by means of time-lapse imaging in living cells. Surprisingly, we found that ERK1 shuttles between the nucleus and cytoplasm at a much slower rate than ERK2. This difference is caused by a domain of ERK1 located at its N-terminus since the progressive deletion of these residues converted the shuttling features of ERK1 into those of ERK2. Conversely, the fusion of this ERK1 sequence at the N-terminus of ERK2 slowed down its shuttling to a similar value found for ERK1. Finally, computational, biochemical and cellular studies indicated that the reduced nuclear shuttling of ERK1 causes a strong reduction of its nuclear phosphorylation compared to ERK2, leading to a reduced capability of ERK1 to carry proliferative signals to the nucleus. This mechanism significantly contributes to the differential ability of ERK1 and 2 to generate an overall signalling output
Convergence of marine megafauna movement patterns in coastal and open oceans
Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115 (2018): 3072-3077, doi:10.1073/pnas.1716137115.The extent of increasing anthropogenic impacts on large marine
vertebrates partly depends on the animals’ movement patterns.
Effective conservation requires identification of the key drivers of
movement including intrinsic properties and extrinsic constraints
associated with the dynamic nature of the environments the animals
inhabit. However, the relative importance of intrinsic versus
extrinsic factors remains elusive. We analyse a global dataset of
2.8 million locations from > 2,600 tracked individuals across 50
marine vertebrates evolutionarily separated by millions of years
and using different locomotion modes (fly, swim, walk/paddle).
Strikingly, movement patterns show a remarkable convergence,
being strongly conserved across species and independent of body
length and mass, despite these traits ranging over 10 orders of
magnitude among the species studied. This represents a fundamental
difference between marine and terrestrial vertebrates not
previously identified, likely linked to the reduced costs of locomotion
in water. Movement patterns were primarily explained by the
interaction between species-specific traits and the habitat(s) they
move through, resulting in complex movement patterns when
moving close to coasts compared to more predictable patterns
when moving in open oceans. This distinct difference may be
associated with greater complexity within coastal micro-habitats,
highlighting a critical role of preferred habitat in shaping marine
vertebrate global movements. Efforts to develop understanding
of the characteristics of vertebrate movement should consider the
habitat(s) through which they move to identify how movement
patterns will alter with forecasted severe ocean changes, such as
reduced Arctic sea ice cover, sea level rise and declining oxygen
content.Workshops funding granted by the UWA Oceans Institute, AIMS, and
KAUST. AMMS was supported by an ARC Grant DE170100841 and an IOMRC
(UWA, AIMS, CSIRO) fellowship; JPR by MEDC (FPU program, Spain); DWS by
UK NERC and Save Our Seas Foundation; NQ by FCT (Portugal); MMCM by
a CAPES fellowship (Ministry of Education)
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