69 research outputs found
High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity
Planet formation studies are often focused on solar-type stars, implicitly
considering our Sun as reference point. This approach overlooks, however, that
Herbig Ae/Be stars are in some sense much better targets to study planet
formation processes empirically, with their disks generally being larger,
brighter and simply easier to observe across a large wavelength range. In
addition, massive gas giant planets have been found on wide orbits around early
type stars, triggering the question if these objects did indeed form there and,
if so, by what process. In the following I briefly review what we currently
know about the occurrence rate of planets around intermediate mass stars,
before discussing recent results from Herbig Ae/Be stars in the context of
planet formation. The main emphasis is put on spatially resolved polarized
light images of potentially planet forming disks and how these images - in
combination with other data - can be used to empirically constrain (parts of)
the planet formation process. Of particular interest are two objects, HD100546
and HD169142, where, in addition to intriguing morphological structures in the
disks, direct observational evidence for (very) young planets has been
reported. I conclude with an outlook, what further progress we can expect in
the very near future with the next generation of high-contrast imagers at 8-m
class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in
special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables
and reference
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 Δ4 allele
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 Δ4 allele
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased AÎČ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
CM-352 Efficacy in a mouse model of anticoagulant-associated intracranial hemorrhage
Background: Intracranial hemorrhage (ICH) is one of the major devastating complications of anticoagulation. Matrix metalloproteinase (MMP) inhibition has been proposed as a novel pharmacological approach for ICH treatment.
Objectives: We evaluated the effects of CM-352 (MMP-fibrinolysis inhibitor) in an experimental ICH model associated with oral anticoagulants as compared with clinically used prothrombin complex concentrate (PCC).
Methods: ICH was induced by collagenase injection into the striatum of wild type (C57BL/6J) anticoagulated mice (warfarin or rivaroxaban) and Mmp10 -/- mice. Hematoma volume and neurological deficits were measured 24 hours later by diaminobenzidine staining and different behavioral tests. Circulating plasminogen activator inhibitor-1 (PAI-1) activity and interleukin-6 (IL-6) were measured in plasma samples and local inflammation was assessed by neutrophil infiltration. Finally, fibrinolytic effects of MMP-10 and rivaroxaban were evaluated by thromboelastometry and thrombin-activatable fibrinolysis inhibitor (TAFI) activation assays.
Results: Only PCC reduced hemorrhage volume and improved functional outcome in warfarin-ICH, but both PCC and CM-352 treatments diminished hemorrhage volume (46%, p < 0.01 and 64%, p < 0.001, respectively) and ameliorated functional outcome in rivaroxaban-ICH. We further demonstrated that CM-352, but not PCC, decreased neutrophil infiltration in the hemorrhage area at 24 hours. The effect of CM-352 could be related to MMP-10 inhibition since Mmp10 -/- mice showed lower hemorrhage volume, better neurological score, reduced IL-6 levels and neutrophil infiltration, and increased PAI-1 after experimental ICH. Finally, we found that CM-352 reduced MMP-10 and rivaroxaban-related fibrinolytic effects in thromboelastometry and TAFI activation.
Conclusion: CM-352 treatment, by diminishing MMPs and rivaroxaban-associated fibrinolytic effects, might be a novel antihemorrhagic strategy for rivaroxaban-associated ICH
Superparamagnetic maghemite loaded poly ([epsilon]- caprolactone) nanocapsules: characterization and synthesis optimization
Iron oxide nanoparticles (ION) have been studied for essential applications, like detection of biological constituents
(virus, bacterials, cell, nucleic acids, protein, enzyme, etc.), magnetic bioseparation and clinic therapy
and diagnosis (such as MRI magnetic fluid and hyperthermia). In this work, Îł-Fe2O3 has been synthetized
by a adapted sol-gel method and entraped in poly Δ-caprolactone (PCL) nanocapsules. The superparamagnetic
nanocapsules have been formulated by double emulsion evaporation method. Some variables affecting the
polydispersity index, zeta potential surface and size of nanocapsules were studied aiming optimize the formulation
process of maghemite-loaded PCL nanocapsules. The following parameters were selected: sonication
time, PCL concentration in organic phase, PVA concentration in external aqueous phase and maghemite/PCL
weight ratio. Under these experimental conditions, the resulting nanocapsules displayed a mean size of about
346 nm and a maghemite content of about 7.5 ÎŒg/mg of nanocapsules and superparamagnetic behaviour at
room temperature
Superparamagnetic maghemite loaded poly ([epsilon]- caprolactone) nanocapsules: characterization and synthesis optimization
Iron oxide nanoparticles (ION) have been studied for essential applications, like detection of biological constituents
(virus, bacterials, cell, nucleic acids, protein, enzyme, etc.), magnetic bioseparation and clinic therapy
and diagnosis (such as MRI magnetic fluid and hyperthermia). In this work, Îł-Fe2O3 has been synthetized
by a adapted sol-gel method and entraped in poly Δ-caprolactone (PCL) nanocapsules. The superparamagnetic
nanocapsules have been formulated by double emulsion evaporation method. Some variables affecting the
polydispersity index, zeta potential surface and size of nanocapsules were studied aiming optimize the formulation
process of maghemite-loaded PCL nanocapsules. The following parameters were selected: sonication
time, PCL concentration in organic phase, PVA concentration in external aqueous phase and maghemite/PCL
weight ratio. Under these experimental conditions, the resulting nanocapsules displayed a mean size of about
346 nm and a maghemite content of about 7.5 ÎŒg/mg of nanocapsules and superparamagnetic behaviour at
room temperature
Optimization of the molecular diagnosis of the acute hepatitis E virus infection
To evaluate the diagnostic value of the combination of two broad-range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV-IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four-hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV-IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad-range PCR assays significantly increased the performance of the molecular diagnosis of HEV
Increasing importance of European lineages in seeding the hepatitis C virus subtype 1a epidemic in Spain
Reducing the burden of the hepatitis C
virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the
dynamic pattern of HCV spread. In Spain, ongoing
transmission of HCV is mostly fuelled by people who
inject drugs (PWID) infected with subtype 1a (HCV1a).
Aim: Our aim was to map how infections spread within
and between populations, which could help formulate
more effective intervention programmes to halt the
HCV1a epidemic in Spain. Methods: Epidemiological
links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected
between 2014 and 2016, and 1,317, 1,291 and 1,009
samples collected abroad between 1989 and 2016
were reconstructed using sequences covering the NS3,
NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to
a flexible Bayesian discrete phylogeographic inference
method. Results: The transmission network structure
of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively
from North America and European countries. The latter
became increasingly relevant and have dominated in
recent times. Export from Spain to other countries in
Europe was also strongly supported, although Spain
was a net sink for European HCV1a lineages. Spatial
reconstructions showed that the epidemic in Spain
is diffuse, without large, dominant within-country
networks. Conclusion: To boost the effectiveness of
local intervention efforts, concerted supra-national
strategies to control HCV1a transmission are needed,
with a strong focus on the most important drivers of
ongoing transmission, i.e. PWID and other high-risk
population
Increasing importance of European lineages in seeding the hepatitis C virus subtype 1a epidemic in Spain
Reducing the burden of the hepatitis C
virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the
dynamic pattern of HCV spread. In Spain, ongoing
transmission of HCV is mostly fuelled by people who
inject drugs (PWID) infected with subtype 1a (HCV1a).
Aim: Our aim was to map how infections spread within
and between populations, which could help formulate
more effective intervention programmes to halt the
HCV1a epidemic in Spain. Methods: Epidemiological
links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected
between 2014 and 2016, and 1,317, 1,291 and 1,009
samples collected abroad between 1989 and 2016
were reconstructed using sequences covering the NS3,
NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to
a flexible Bayesian discrete phylogeographic inference
method. Results: The transmission network structure
of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively
from North America and European countries. The latter
became increasingly relevant and have dominated in
recent times. Export from Spain to other countries in
Europe was also strongly supported, although Spain
was a net sink for European HCV1a lineages. Spatial
reconstructions showed that the epidemic in Spain
is diffuse, without large, dominant within-country
networks. Conclusion: To boost the effectiveness of
local intervention efforts, concerted supra-national
strategies to control HCV1a transmission are needed,
with a strong focus on the most important drivers of
ongoing transmission, i.e. PWID and other high-risk
population
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