Scope. Milk provides a natural means of nutrient supply to infants. Exosomes are an important component of milk that are not only being studied for their promise in translational medicine but also in ...infant nutrition. They also play important roles in intercellular communication and immune function in mammary glands and are able to transfer their materials to the recipient. Therefore, the isolation of high-quality exosomes is an important aspect of exosome research. Methods and Results. This study is a technical study, which provides a detailed methodology for the isolation and enrichment of exosomes from milk. In this study, we evaluate the suitability of using the exosome enrichment method that we have recently published for bovine milk, on human milk. We initially isolated extracellular vesicles from human and bovine milk on a fresh set of samples, using ultracentrifugation, and then exosomes were subsequently enriched via size exclusion chromatography (SEC). Following isolation and enrichment, exosomes from both species were characterized by particle concentration (nanoparticle tracking analysis, NTA), morphology (transmission electron microscopy, TEM), and the presence of exosomal markers (immunoblotting and mass spectrometry using information dependant acquisition (IDA)). The key exosomal characteristics of spherical/donut-shaped morphology, the presence of exosomal markers, e.g., FLOT-1 and the tetraspanins, CD9 and CD81), and particle concentration were confirmed in both human and bovine milk exosomes. Conclusion. We conclude that our robust exosome enrichment method, previously published for bovine milk, is suitable for use on human milk.
Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the ...degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.
We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.
Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.
Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.
The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ).
The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.
Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation.
To assess efficacy of fecal microbiome ...transfer (FMT) to treat adolescent obesity and improve metabolism.
This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020.
Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo.
Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition.
Eighty-seven participants (59% female adolescents, mean SD age 17.2 1.4 years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference aMD -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial.
In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.
Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
New detections of debris discs at submillimetre wavelengths present highly valuable complementary information to prior observations of these sources at shorter wavelengths. Characterization of discs ...through spectral energy distribution modelling including the submillimetre fluxes is essential for our basic understanding of disc mass and temperature, and presents a starting point for further studies using millimetre interferometric observations. In the framework of the ongoing SCUBA-2 Observations of Nearby Stars, the instrument SCUBA-2 on the James Clerk Maxwell Telescope was used to provide measurements of 450 and 850 μm fluxes towards a large sample of nearby main-sequence stars with debris discs detected previously at shorter wavelengths. We present the first results from the ongoing survey, concerning 850 μm detections and 450 μm upper limits towards 10 stars, the majority of which are detected at submillimetre wavelengths for the first time. One, or possibly two, of these new detections is likely a background source. We fit the spectral energy distributions of the star+disc systems with a blackbody emission approach and derive characteristic disc temperatures. We use these temperatures to convert the observed fluxes to disc masses. We obtain a range of disc masses from 0.001 to 0.1 M⊕, values similar to the prior dust mass measurements towards debris discs. There is no evidence for evolution in dust mass with age on the main sequence, and indeed the upper envelope remains relatively flat at 0.5 M⊕ at all ages. The inferred disc masses are lower than those from disc detections around pre-main-sequence stars, which may indicate a depletion of solid mass. This may also be due to a change in disc opacity, though limited sensitivity means that it is not yet known what fraction of pre-main-sequence stars have discs with dust masses similar to debris disc levels. New, high-sensitivity detections are a path towards investigating the trends in dust mass evolution.
τ Ceti is a nearby, mature G-type star very similar to our Sun, with a massive Kuiper Belt analogue and possible multiplanet system that has been compared to our Solar system. We present Herschel ...Space Observatory images of the debris disc, finding the disc is resolved at 70 μm and 160 μm, and marginally resolved at 250 μm. The Herschel images and infrared photometry from the literature are best modelled using a wide dust annulus with an inner edge between 1 and 10 au and an outer edge at ∼55 au, inclined from face-on by 35° ± 10°, and with no significant azimuthal structure. We model the proposed tightly packed planetary system of five super-Earths and find that the innermost dynamically stable disc orbits are consistent with the inner edge found by the observations. The photometric modelling, however, cannot rule out a disc inner edge as close to the star as 1 au, though larger distances produce a better fit to the data. Dynamical modelling shows that the five-planet system is stable with the addition of a Neptune or smaller mass planet on an orbit outside 5 au, where the radial velocity data analysis would not have detected a planet of this mass.
Abstract
The presence of dusty debris around main-sequence stars denotes the existence of planetary systems. Such debris discs are often identified by the presence of excess continuum emission at ...infrared and (sub-)millimetre wavelengths, with measurements at longer wavelengths tracing larger and cooler dust grains. The exponent of the slope of the disc emission at submillimetre wavelengths, ‘q’, defines the size distribution of dust grains in the disc. This size distribution is a function of the rigid strength of the dust producing parent planetesimals. As a part of the survey ‘PLAnetesimals around TYpical Pre-main seqUence Stars’, we observed six debris discs at 9 mm using the Australian Telescope Compact Array. We obtain marginal (∼3σ) detections of three targets: HD 105, HD 61005 and HD 131835. Upper limits for the three remaining discs, HD 20807, HD 109573 and HD 109085 provide further constraint of the (sub-)millimetre slope of their spectral energy distributions. The values of q (or their limits) derived from our observations are all smaller than the oft-assumed steady-state collisional cascade model (q = 3.5), but lie well within the theoretically expected range for debris discs q ∼ 3–4. The measured q values for our targets are all <3.3, consistent with both collisional modelling results and theoretical predictions for parent planetesimal bodies being ‘rubble piles’ held together loosely by their self-gravity.
To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2.
Adaptive optics ...scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss.
Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units au) increased with increasing eccentricity (slope = 0.054 au/degree, r(2) = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT.
Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.).
Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets. Collisions between such bodies produce small dust particles, the spectral features of which reveal ...their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg(2-2x)Fe(2x)SiO(4)) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids (x ≈ 0.29). In the cold outskirts of the β Pictoris system, an analogue to the young Solar System, olivine crystals were detected but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets. Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of β Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 ± 0.001) and show that they make up 3.6 ± 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System, even though β Pictoris is more massive and more luminous and has a different planetary system architecture.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SCUBA, the Submillimetre Common-User Bolometer Array, built by the Royal Observatory Edinburgh for the James Clerk Maxwell Telescope, is the most versatile and powerful of a new generation of ...submillimetre cameras. It combines a sensitive dual-waveband imaging array with a three-band photometer, and is sky-background-limited by the emission from the Mauna Kea atmosphere at all observing wavelengths from 350 μμto 2 mm. The increased sensitivity and array size mean that SCUBA maps close to 10 000 times faster than its single-pixel predecessor (UKT14). SCUBA is a facility instrument, open to the world community of users, and is provided with a high level of user support. We give an overview of the instrument, describe the observing modes, user interface and performance figures on the telescope, and present a sample of the exciting new results that have revolutionized submillimetre astronomy.
We present high spatial resolution mid- and far-infrared images of the Vega debris disk obtained with the Multiband Imaging Photometer for Spitzer (MIPS). The disk is well resolved, and its angular ...size is much larger than found previously. The radius of the disk is at least 43" (330 AU), 70" (543 AU), and 105" (815 AU) in extent at 24, 70, and 160 km, respectively. The disk images are circular, smooth, and without clumpiness at all three wavelengths. The radial surface brightness profiles follow radial power laws of r super(-3) or r super(-4) and imply an inner boundary at a radius of 11" c 2" (86 AU). Assuming an amalgam of amorphous silicate and carbonaceous grains, the disk can be modeled as an axially symmetric and geometrically thin disk, viewed face-on, with the surface particle number density following an inverse radial power law. The disk radiometric properties are consistent with a range of models using grains of sizes 61 to 650 km. The exact minimum and maximum grain size limits depend on the adopted grain composition. However, all of these models require an r super(-1) surface number density profile and a total mass of (3 c 1.5) x 10 super(-3) M sub( )in grains. We find that a ring, containing grains larger than 180 km and at radii of 86-200 AU from the star, can reproduce the observed 850 km flux, while its emission does not violate the observed MIPS profiles. This ring could be associated with a population of larger asteroidal bodies analogous to our own Kuiper Belt. Cascades of collisions starting with encounters among these large bodies in the ring produce the small debris that is blown outward by radiation pressure to much larger distances, where we detect its thermal emission. The relatively short lifetime (<1000 yr) of these small grains and the observed total mass, 63 x 10 super(-3) M sub( ), set a lower limit on the dust production rate, 610 super(15) g s super(-1). This rate would require a very massive asteroidal reservoir for the dust to be produced in a steady state throughout Vega's life. Instead, we suggest that the disk we imaged is ephemeral and that we are witnessing the aftermath of a large and relatively recent collisional event, and a subsequent collisional cascade.
PDF
