496 research outputs found
Bronchopulmonary Dysplasia
Hospitalizations for respiratory syncytial virus bronchioliti
RACE-OC Project: Rotation and variability in the open cluster M11 (NGC6705)
Rotation and magnetic activity are intimately linked in main-sequence stars
of G or later spectral types. The presence and level of magnetic activity
depend on stellar rotation, and rotation itself is strongly influenced by
strength and topology of the magnetic fields. Open clusters represent
especially useful targets to investigate the rotation/activity/age connection.
The open cluster M11 has been studied as a part of the RACE-OC project
(Rotation and ACtivity Evolution in Open Clusters), which is aimed at exploring
the evolution of rotation and magnetic activity in the late-type members of
open clusters with different ages. Photometric observations of the open cluster
M11 were carried out in June 2004 using LOAO 1m telescope. The rotation periods
of the cluster members are determined by Fourier analysis of photometric data
time series. We further investigated the relations between the surface
activity, characterized by the light curve amplitude, and rotation. We have
discovered a total of 75 periodic variables in the M11 FoV, of which 38 are
candidate cluster members. Specifically, among cluster members we discovered 6
early-type, 2 eclipsing binaries and 30 bona-fide single periodic late-type
variables. Considering the rotation periods of 16 G-type members of the almost
coeval 200-Myr M34 cluster, we could determine the rotation period distribution
from a more numerous sample of 46 single G stars at an age of about 200-230 Myr
and determine a median rotation period P=4.8d. A comparison with the younger
M35 cluster (~150 Myr) and with the older M37 cluster (~550 Myr) shows that G
stars rotate slower than younger M35 stars and faster than older M37 stars. The
measured variation of the median rotation period is consistent with the
scenario of rotational braking of main-sequence spotted stars as they age.Comment: Accepted by Astronomy and Astrophysics on Dec 15, 200
Altruism can proliferate through group/kin selection despite high random gene flow
The ways in which natural selection can allow the proliferation of
cooperative behavior have long been seen as a central problem in evolutionary
biology. Most of the literature has focused on interactions between pairs of
individuals and on linear public goods games. This emphasis led to the
conclusion that even modest levels of migration would pose a serious problem to
the spread of altruism in group structured populations. Here we challenge this
conclusion, by analyzing evolution in a framework which allows for complex
group interactions and random migration among groups. We conclude that
contingent forms of strong altruism can spread when rare under realistic group
sizes and levels of migration. Our analysis combines group-centric and
gene-centric perspectives, allows for arbitrary strength of selection, and
leads to extensions of Hamilton's rule for the spread of altruistic alleles,
applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26
figure
Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin
AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA(1c) changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA(1c), blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA(1c) and change in HbA(1c) on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA(1c) and higher diastolic BP at baseline. There was a larger reduction in HbA(1c) at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA(1c) (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA(1c) at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA(1c). Progression of diabetic retinopathy over 3 years was not associated with a change in HbA(1c). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05456-w
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Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens
Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae
A Quantitative Test of Hamilton's Rule for the Evolution of Altruism
A study of experimental evolution in simulated groups of foraging robots demonstrates that their propensity to behave altruistically depends on their genetic relatedness (similarity), and the costs and benefits associated with altruistic behavior
Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators
<p>Abstract</p> <p>Background</p> <p>Tetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD) demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (<it>Neurology </it>2006;66:366-372). The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD.</p> <p>Methods</p> <p>Subjects who completed the 13-week, double blind protocol were invited to participate in this open label extension study for up to 80 weeks. Subjects were titrated to the best individual dose or a maximum of 200 mg/day. Chorea was assessed using the Total Maximal Chorea (TMC) score from the Unified Huntington Disease Rating Scale.</p> <p>Results</p> <p>Of the 75 participants, 45 subjects completed 80 weeks. Three participants terminated due to adverse events (AEs) including depression, delusions with associated previous suicidal behavior, and vocal tics. One subject died due to breast cancer. The other 26 subjects chose not to continue on with each ensuing extension for various reasons. When mild and unrelated AEs were excluded, the most commonly reported AEs (number of subjects) were sedation/somnolence (18), depressed mood (17), anxiety (13), insomnia (10), and akathisia (9). Parkinsonism and dysphagia scores were significantly increased at week 80 compared to baseline. At week 80, chorea had significantly improved from baseline with a mean reduction in the TMC score of 4.6 (SD 5.5) units. The mean dosage at week 80 was 63.4 mg (range 12.5-175 mg).</p> <p>Conclusions</p> <p>TBZ effectively suppresses HD-related chorea for up to 80 weeks. Patients treated chronically with TBZ should be monitored for parkinsonism, dysphagia and other side effects including sleep disturbance, depression, anxiety, and akathisia.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov registration number (initial study): NCT00219804</p
FOXL2 and TERT promoter mutation detection in circulating tumor DNA of adult granulosa cell tumors as biomarker for disease monitoring
OBJECTIVE: Adult granulosa cell tumors (aGCTs) represent a rare, hormonally active subtype of ovarian cancer that has a tendency to relapse late and repeatedly. Current serum hormone markers are inaccurate in reflecting tumor burden in a subset of aGCT patients, indicating the need for a novel biomarker. We investigated the presence of circulating tumor DNA (ctDNA) harboring a FOXL2 or TERT promoter mutation in serial plasma samples of aGCT patients to determine its clinical value for monitoring disease. METHODS: In a national multicenter study, plasma samples (n = 110) were prospectively collected from 21 patients with primary (n = 3) or recurrent (n = 18) aGCT harboring a FOXL2 402C > G and/or TERT (C228T or C250T) promoter mutation. Circulating cell-free DNA was extracted and assessed for ctDNA containing one of either mutations using droplet digital PCR (ddPCR). Fractional abundance of FOXL2 mutant and TERT mutant ctDNA was correlated with clinical parameters. RESULTS: FOXL2 mutant ctDNA was found in plasma of 11 out of 14 patients (78.6%) with aGCT with a confirmed FOXL2 mutation. TERT C228T or TERT C250T mutant ctDNA was detected in plasma of 4 of 10 (40%) and 1 of 2 patients, respectively. Both FOXL2 mutant ctDNA and TERT promoter mutant ctDNA levels correlated with disease progression and treatment response in the majority of patients. CONCLUSIONS: FOXL2 mutant ctDNA was present in the majority of aGCT patients and TERT promoter mutant ctDNA has been identified in a smaller subset of patients. Both FOXL2 and TERT mutant ctDNA detection may have clinical value in disease monitoring
A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism
Background: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy‐to‐use clinical screening tool to help recognize movement disorders.
Objective: The aim is to develop a user‐friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.
Methods: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter‐rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.
Results: A movement disorder was rated as present in 80% of the patients, with a moderate inter‐rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter‐rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool.
Conclusions: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder.
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus
During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease
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