ABSTRACT
The recently discovered colliding-wind binary (CWB) Apep has been shown to emit luminously from radio to X-rays, with the emission driven by a binary composed of two Wolf–Rayet (WR) stars of ...one carbon-sequence (WC8) and one nitrogen-sequence (WN4–6b). Mid-infrared imaging revealed a giant spiral dust plume that is reminiscent of a pinwheel nebula but with additional features that suggest Apep is a unique system. We have conducted observations with the Australian Long Baseline Array to resolve Apep’s radio emission on milliarcsecond scales, allowing us to relate the geometry of the wind-collision region to that of the spiral plume. The observed radio emission shows a bow-shaped structure, confirming its origin as a wind-collision region. The shape and orientation of this region is consistent with being originated by the two stars and with being likely dominated by the stronger wind of the WN4–6b star. This shape allowed us to provide a rough estimation of the opening angle of ∼150○ assuming ideal conditions. The orientation and opening angle of the emission also confirms it as the basis for the spiral dust plume. We also provide estimations for the two stars in the system to milliarcsecond precision. The observed radio emission, one order of magnitude brighter and more luminous than any other known non-thermal radio-emitting CWB, confirms it is produced by an extremely powerful wind collision. Such a powerful wind-collision region is consistent with Apep being a binary composed of two WR stars, so far the first unambiguously confirmed system of its kind.
Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases including neurodegenerative ones, particularly Alzheimer's ...disease (AD). These compounds, known as nutraceuticals, differ structurally, act therefore at different biochemical and metabolic levels and have shown different types of neuroprotective properties. The aim of this review is to summarize data from observational studies, clinical trials, and randomized clinical trials (RCTs) in humans on the effects of selected nutraceuticals against age-related cognitive impairment and dementia. We report results from studies on flavonoids, some vitamins and other natural substances that have been studied in AD and that might be beneficial for the maintenance of a good cognitive performance. Due to the substantial lack of high-level evidence studies there is no possibility for recommendation of nutraceuticals in dementia-related therapeutic guidelines. Nevertheless, the strong potential for their neuroprotective action warrants further studies in the field.
For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this ...recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH).
We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH.
The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH.
http://www.clinicaltrials.gov. Unique identifier: NCT01347216.
Aims. The Spectral and Photometric Imaging REceiver (SPIRE) onboard the Herschel space telescope has provided confusion limited maps of deep fields at 250 μm, 350 μm, and 500 μm, as part of the ...Herschel Multi-tiered Extragalactic Survey (HerMES). Unfortunately, due to confusion, only a small fraction of the cosmic infrared background (CIB) can be resolved into individually-detected sources. Our goal is to produce deep galaxy number counts and redshift distributions below the confusion limit at SPIRE wavelengths (~20 mJy), which we then use to place strong constraints on the origins of the cosmic infrared background and on models of galaxy evolution. Methods. We individually extracted the bright SPIRE sources (>20 mJy) in the COSMOS field with a method using the positions, the flux densities, and the redshifts of the 24 μm sources as a prior, and derived the number counts and redshift distributions of the bright SPIRE sources. For fainter SPIRE sources (<20 mJy), we reconstructed the number counts and the redshift distribution below the confusion limit using the deep 24 μm catalogs associated with photometric redshift and information provided by the stacking of these sources into the deep SPIRE maps of the GOODS-N and COSMOS fields. Finally, by integrating all these counts, we studied the contribution of the galaxies to the CIB as a function of their flux density and redshift. Results. Through stacking, we managed to reconstruct the source counts per redshift slice down to ~2 mJy in the three SPIRE bands, which lies about a factor 10 below the 5σ confusion limit. Our measurements place tight constraints on source population models. None of the pre-existing models are able to reproduce our results at better than 3-σ. Finally, we extrapolate our counts to zero flux density in order to derive an estimate of the total contribution of galaxies to the CIB, finding 10.1-2.3+2.6 nW m-2 sr-1, 6.5-1.6+1.7 nW m-2 sr-1, and 2.8-0.8+0.9 nW m-2 sr-1 at 250 μm, 350 μm, and 500 μm, respectively. These values agree well with FIRAS absolute measurements, suggesting our number counts and their extrapolation are sufficient to explain the CIB. We find that half of the CIB is emitted at z = 1.04, 1.20, and 1.25, respectively. Finally, combining our results with other works, we estimate the energy budget contained in the CIB between 8 μm and 1000 μm: 26-3+7 nW m-2 sr-1.
Plants and insects often use the same compounds for chemical communication, but not much is known about the genetics of convergent evolution of chemical signals. The terpene (E)-β-ocimene is a common ...component of floral scent and is also used by the butterfly Heliconius melpomene as an anti-aphrodisiac pheromone. While the biosynthesis of terpenes has been described in plants and microorganisms, few terpene synthases (TPSs) have been identified in insects. Here, we study the recent divergence of 2 species, H. melpomene and Heliconius cydno, which differ in the presence of (E)-β-ocimene; combining linkage mapping, gene expression, and functional analyses, we identify 2 novel TPSs. Furthermore, we demonstrate that one, HmelOS, is able to synthesise (E)-β-ocimene in vitro. We find no evidence for TPS activity in HcydOS (HmelOS ortholog of H. cydno), suggesting that the loss of (E)-β-ocimene in this species is the result of coding, not regulatory, differences. The TPS enzymes we discovered are unrelated to previously described plant and insect TPSs, demonstrating that chemical convergence has independent evolutionary origins.
Silver–Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and ...several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately, half of all patients exhibit DNA hypomethylation at the
H19/IGF2
imprinted domain, and around 10 % have maternal uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel bioinformatics methodology specifically designed to identify subsets of patients with a shared epimutation, we analysed methylation changes genome-wide as well as at known imprinted regions to identify SRS-associated epimutations. Our analysis identifies epimutations at the previously characterised domains of
H19/IGF2
and at imprinted regions on chromosome 7, providing proof of principle that our methodology can detect DNA methylation changes at imprinted loci. In addition, we discovered two novel epimutations associated with SRS and located at imprinted loci previously linked to relevant mouse and human phenotypes. We identify
RB1
as an additional imprinted locus associated with SRS, with a region near the
RB1
differentially methylated region hypermethylated in 13/18 (~70 %) patients. We also report 6/18 (~33 %) patients were hypermethylated at a CpG island near the
ANKRD11
gene. We do not observe consistent co-occurrence of epimutations at multiple imprinted loci in single SRS individuals. SRS is clinically heterogeneous and the absence of multiple imprinted loci epimutations reflects the heterogeneity at the molecular level. Further stratification of SRS patients by molecular phenotypes might aid the identification of disease causes.
The effect of window material on electron beam induced phenomena in liquid phase electron microscopy (LPEM) is an interesting yet under-explored subject. We have studied the differences of electron ...beam induced gold nanoparticle (AuNP) growth subject to three encapsulation materials: Silicon Nitride (Si3N4), carbon and formvar. We find Si3N4 liquid cells (LCs) to result in significantly higher AuNP growth yield as compared to LCs employing the other two materials. In all cases, an electrical bias of the entire LC structures significantly affected particle growth. We demonstrate an inverse correlation of the AuNP growth rate with secondary electron (SE) emission from the windows. We attribute these differences at least in part to variations in SE emission dynamics, which is seen as a combination of material and bias dependent SE escape flux (SEEF) and SE return flux (SERF). Furthermore, our model predictions qualitatively match electrochemistry expectations.
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The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates ...and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.
Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease ...progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA.
200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers.
Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression.
ClinicalTrails.gov Identifier: NCT04349514.
Objective
The progression of Alzheimer’s disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the ...progression of AD. DBS is an approved method in the treatment of Parkinson’s disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.
Design
A 1-year phase I proof-of-concept study.
Setting
The Department of Psychiatry and Psychotherapy at the University of Cologne.
Participants
We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. Intervention: Bilateral low-frequency DBS of the nucleus basalis of Meynert.
Measurements
Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.
Results
With a normal body mass index (BMI) at baseline (mean 23.75 kg/m
2
) and after 1 year (mean 24.59 kg/m
2
), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = −0.829, p = 0.042).
Conclusion
Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.
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