726 research outputs found
ON THE ORIGIN OF THE NEAR-INFRARED EMISSION FROM THE NEUTRON-STAR LOW-MASS X-RAY BINARY GX 9+1
We have determined an improved position for the luminous persistent neutron-star low-mass X-ray binary and atoll source GX 9+1 from archival Chandra X-ray Observatory data. The new position significantly differs from a previously published Chandra position for this source. Based on the revised X-ray position we have identified a new near-infrared (NIR) counterpart to GX 9+1 in K[subscript s]-band images obtained with the PANIC and FourStar cameras on the Magellan Baade Telescope. NIR spectra of this K[subscript s]=16.5 ± 0.1 mag star, taken with the FIRE spectrograph on the Baade Telescope, show a strong Br γ emission line, which is a clear signature that we discovered the true NIR counterpart to GX 9+1. The mass donor in GX 9+1 cannot be a late-type giant, as such a star would be brighter than the estimated absolute Ks magnitude of the NIR counterpart. The slope of the dereddened NIR spectrum is poorly constrained due to uncertainties in the column density NH and NIR extinction. Considering the source's distance and X-ray luminosity, we argue that NH likely lies near the high end of the previously suggested range. If this is indeed the case, the NIR spectrum is consistent with thermal emission from a heated accretion disk, possibly with a contribution from the secondary. In this respect, GX 9+1 is similar to other bright atolls and the Z sources, whose NIR spectra do not show the slope that is expected for a dominant contribution from optically thin synchrotron emission from the inner regions of a jet
Discovery of the near-infrared counterpart to the luminous neutron-star low-mass X-ray binary GX 3+1
Using the High Resolution Camera onboard the Chandra X-ray Observatory, we
have measured an accurate position for the bright persistent neutron-star X-ray
binary and atoll source GX 3+1. At a location that is consistent with this new
position we have discovered the near-infrared (NIR) counterpart to GX 3+1 in
images taken with the PANIC and FourStar cameras on the Magellan Baade
Telescope. The identification of this K_s=15.8+-0.1 mag star as the counterpart
is based on the presence of a Br-gamma emission line in a NIR spectrum taken
with the FIRE spectrograph on the Baade Telescope. The absolute magnitude
derived from the best available distance estimate to GX 3+1 indicates that the
mass donor in the system is not a late-type giant. We find that the NIR light
in GX 3+1 is likely dominated by the contribution from a heated outer accretion
disk. This is similar to what has been found for the NIR flux from the brighter
class of Z sources, but unlike the behavior of atolls fainter (Lx ~ 1e36 to
1e37 erg/s) than GX 3+1, where optically-thin synchrotron emission from a jet
probably dominates the NIR flux.Comment: Accepted for publication in Ap
Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats
rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability
Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways
Amyotrophic lateral sclerosis (ALS) is a devastating
neurological disease with no effective treatment
available. An increasing number of genetic causes of ALS
are being identified, but how these genetic defects lead to
motor neuron degeneration and to which extent they affect
common cellular pathways remains incompletely understood.
To address these questions, we performed an interactomic
analysis to identify binding partners of wild-type
(WT) and ALS-associated mutant versions of ATXN2,
C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal
cells. This analysis identified several known but also many
novel binding partners of these proteins
Willingness to participate in a lifestyle intervention program of patients with type 2 diabetes mellitus: a conjoint analysis
Background: Several studies suggest that lifestyle interventions can be effective for people with, or at risk for, diabetes. The participation in lifestyle interventions is generally low. Financial incentives may encourage participation in lifestyle intervention programs. Objetive: The main aim of this exploratory analysis is to study empirically potential effects of financial incentives on diabetes patients' willingness to participate in lifestyle interventions. One financial incentive is negative ("copayment") and the other incentive is positive ("bonus"). The key part of this research is to contrast both incentives. The second aim is to investigate the factors that influence participation in a lifestyle intervention program. Methods: Conjoint analysis techniques were used to empirically identify factors that influence willingness to participate in a lifestyle intervention. For this purpose diabetic patients received a questionnaire with descriptions of various forms of hypothetical lifestyle interventions. They were asked if they would be willing to participate in these hypothetical programs. Results: In total, 174 observations were rated by 46 respondents. Analysis showed that money was an important factor independently associated with respondents' willingness to participate. Receiving a bonus seemed to be associated with a higher willingness to participate, but having to pay was negatively associated with participation in the lifestyle intervention. Conclusion: Conjoint analysis results suggest that financial considerations may influence willingness to participate in lifestyle intervention programs. Financial disincentives in the form of copayments might discourage participation. Although the positive impact of bonuses is smaller than the negative impact of copayments, bonuses could still be used to encourage willingness to participate
Genetics of Amyotrophic Lateral Sclerosis
La sclĂ©rose latĂ©rale amyotrophique (SLA) est la maladie des neurones moteurs la plus frĂ©quente, affectant 4-6 individus par 100,000 habitants Ă lâĂ©chelle mondiale. La maladie se caractĂ©rise par une faiblesse et une atrophie musculaire suite Ă la dĂ©gĂ©nĂ©rescence des neurones du cortex moteur, tronc cĂ©rĂ©bral et moelle Ă©piniĂšre. Les personnes atteintes dĂ©veloppent les premiers symptĂŽmes Ă lâĂąge adulte et la maladie progresse sur une pĂ©riode de trois Ă cinq ans. Il a Ă©tĂ© rĂ©pertoriĂ© quâenviron 10% des patients ont une histoire familiale de SLA; 90% des gens affectĂ©s le sont donc de façon sporadique. La dĂ©couverte il y a 19 ans de mutations dans le gĂšne zinc/copper superoxide dismutase (SOD1), prĂ©sentes dans 15-20% des cas familiaux de SLA et environ 2% du total des individus affectĂ©s, a Ă©tĂ© lâĂ©vĂ©nement dĂ©clencheur pour la dĂ©couverte de variations gĂ©nĂ©tiques responsables de la maladie. La recherche sur la gĂ©nĂ©tique de la SLA a connu une progression rapide ces quatre derniĂšres annĂ©es avec lâidentification de mutations dans de nouveaux gĂšnes. Toutefois, mĂȘme si certains de ces gĂšnes ont Ă©tĂ© dĂ©montrĂ©s comme rĂ©ellement liĂ©s Ă la maladie, la contribution dâautres gĂšnes demeure incertaine puisque les rĂ©sultats publiĂ©s de ceux-ci nâont pas, Ă ce jour, Ă©tĂ© rĂ©pliquĂ©s. Une portion substantielle de cas reste cependant Ă ĂȘtre gĂ©nĂ©tiquement expliquĂ©e, et aucun traitement Ă ce jour nâa Ă©tĂ© dĂ©montrĂ© comme Ă©tant efficace pour remĂ©dier, attĂ©nuer ou prĂ©venir la maladie.
Le but du projet de recherche de doctorat Ă©tait dâidentifier de nouveaux gĂšnes mutĂ©s dans la SLA, tout en Ă©valuant la contribution de gĂšnes nouvellement identifiĂ©s chez une importante cohorte multiethnique de cas familiaux et sporadiques. Les rĂ©sultats prĂ©sentĂ©s sont organisĂ©s en trois sections diffĂ©rentes. Dans un premier temps, la contribution de mutations prĂ©sentes dans le gĂšne FUS est Ă©valuĂ©e chez les patients familiaux, sporadiques et juvĂ©niles de SLA. PrĂ©cisĂ©ment, de nouvelles mutations sont rapportĂ©es et la proportion de mutations retrouvĂ©es chez les cas familiaux et sporadiques de SLA est Ă©valuĂ©e. De plus, une nouvelle mutation est rapportĂ©e dans un cas juvĂ©nile de SLA; cette Ă©tude de cas est discutĂ©e. Dans un deuxiĂšme temps, de nouvelles avenues gĂ©nĂ©tiques sont explorĂ©es concernant le gĂšne SOD1. En effet, une nouvelle mutation complexe est rapportĂ©e chez une famille française de SLA. De plus, la possibilitĂ© quâune mutation prĂ©sente dans un autre gĂšne impliquĂ© dans la SLA ait un impact sur lâĂ©pissage du gĂšne SOD1 est Ă©valuĂ©e. Finalement, la derniĂšre section explique la contribution de nouveaux gĂšnes candidats chez les patients atteints de SLA. SpĂ©cifiquement, le rĂŽle des gĂšnes OPTN, SIGMAR1 et SORT1 dans le phĂ©notype de SLA est Ă©valuĂ©.
Il est souhaitĂ© que nos rĂ©sultats combinĂ©s avec les rĂ©cents dĂ©veloppements en gĂ©nĂ©tique et biologie molĂ©culaire permettent une meilleure comprĂ©hension du mĂ©canisme pathologique responsable de cette terrible maladie tout en guidant le dĂ©ploiement de thĂ©rapies suite Ă lâidentification des cibles appropriĂ©es.Amyotrophic lateral sclerosis (ALS) is the most common of motor neuron diseases, affecting 4-6 individuals per 100,000 individuals worldwide. ALS is characterized by muscle weakness and atrophy caused by the degeneration of neurons located in the motor cortex, brain stem and spinal cord. This fatal disease generally has an adult onset and progresses over a three to five year period. While 10% of patients affected have a family history of the disease, 90% of cases do not and are considered sporadic. The finding of mutations in the zinc/copper superoxide dismutase gene (SOD1) gene 19 years ago in about 15-20% of familial ALS (FALS) patients and approximately 2% of overall cases developed the interest of identifying rare genetics variants causing the disease. The ALS research field experienced a rapid progression during the last four years as mutations in new genes have been identified. While mutations in some of those new genes have been clearly linked to ALS, the role of others is still questionable and so far has not been positively replicated in other populations. Importantly, a significant portion of cases still need to be genetically explained and, unfortunately, there is still no effective treatment to cure, attenuate or prevent the disease.
The aim of this Ph.D research project was to identify new ALS mutated genes while analysing the causative role of other newly identified genes in a large familial and sporadic ALS cohort of different origins. The results presented here are categorized into three different sections. First, the contribution of FUS mutations to familial, sporadic and juvenile ALS is analysed. Specifically, new FUS mutations are reported in ALS cases and the proportions of variants present in the tested familial and sporadic ALS cohorts are assessed. In addition, a new mutation is reported in a juvenile ALS patient, and this interesting case is discussed. Second, new genetic avenues are explored for the SOD1 gene. Precisely, a new and complex SOD1 mutation is reported in a French ALS family. Moreover, the possibility that other ALS mutated genes influence SOD1 splicing events is evaluated. Third, the contribution of new candidate genes is evaluated. Precisely, the contribution of OPTN, SIGMAR1 and SORT1 genes to the ALS phenotype is assessed.
Hopefully, our different findings combined with recent developments in genetics and molecular biology will permit a better understanding of the pathological mechanisms involved in the disease and will lead to the identification of the right targets in order to develop appropriate therapeutics for ALS patients
De EnergyBarn:publiekscentrum energy transitie center
De EnergyBarn is een lokaal duurzaam multidisciplinair project tussen educatie, overheid en het bedrijfsleven. De EnergyBarn is bedoeld als publiekspunt waar ontwikkelingen kunnen worden getoond aan de maatschappij. De burger kan deze ontwikkelingen ontmoeten en aanraken. De Energy Barn wordt in opdracht van EnTranCe gebouwd met bijdragen van de partners
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