Secretory immunoglobulin A (sIgA) plays an important role in gut barrier protection by shaping the resident microbiota community, restricting the growth of bacterial pathogens and enhancing host ...protective immunity via immunological exclusion. Here, we found that a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi. Analysis of the human gut mycobiota bound by sIgA revealed a preference for hyphae, a fungal morphotype associated with virulence. Candida albicans was a potent inducer of IgA class-switch recombination among plasma cells, via an interaction dependent on intestinal phagocytes and hyphal programming. Characterization of sIgA affinity and polyreactivity showed that hyphae-associated virulence factors were bound by these antibodies and that sIgA influenced C. albicans morphotypes in the murine gut. Furthermore, an increase in granular hyphal morphologies in patients with Crohn's disease compared with healthy controls correlated with a decrease in antifungal sIgA antibody titre with affinity to two hyphae-associated virulence factors. Thus, in addition to its importance in gut bacterial regulation, sIgA targets the uniquely fungal phenomenon of hyphal formation. Our findings indicate that antifungal sIgA produced in the gut can play a role in regulating intestinal fungal commensalism by coating fungal morphotypes linked to virulence, thereby providing a protective mechanism that might be dysregulated in patients with Crohn's disease.
IMPORTANCE Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. ...OBJECTIVE To describe 10-year progression rates to intermediate or advanced AMD. DESIGN, SETTING, AND PARTICIPANTS We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years. EXPOSURE Treatment with antioxidant vitamins and minerals. MAIN OUTCOMES AND MEASURES Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits. RESULTS The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200. CONCLUSIONS AND RELEVANCE The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.
Abstract
Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An ...unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise,
n
= 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX
n
= 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control;
n
= 35, MOD-EX;
n
= 31, and VIG-EX;
n
= 31). We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6 ml; Δ MOD-EX: −15.5 ± 62.1 ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or
18
F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1 ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1;
p
= 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.
Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. In this 6-month randomized, multicenter trial involving such patients, a closed-loop ...system led to a greater percentage of time with the glucose level in a target range than did a sensor-augmented insulin pump.
The 2017–2027 National Academies' Decadal Survey, Thriving on Our Changing Planet, recommended Surface Biology and Geology (SBG) as a “Designated Targeted Observable” (DO). The SBG DO is based on the ...need for capabilities to acquire global, high spatial resolution, visible to shortwave infrared (VSWIR; 380–2500 nm; ~30 m pixel resolution) hyperspectral (imaging spectroscopy) and multispectral midwave and thermal infrared (MWIR: 3–5 μm; TIR: 8–12 μm; ~60 m pixel resolution) measurements with sub-monthly temporal revisits over terrestrial, freshwater, and coastal marine habitats. To address the various mission design needs, an SBG Algorithms Working Group of multidisciplinary researchers has been formed to review and evaluate the algorithms applicable to the SBG DO across a wide range of Earth science disciplines, including terrestrial and aquatic ecology, atmospheric science, geology, and hydrology. Here, we summarize current state-of-the-practice VSWIR and TIR algorithms that use airborne or orbital spectral imaging observations to address the SBG DO priorities identified by the Decadal Survey: (i) terrestrial vegetation physiology, functional traits, and health; (ii) inland and coastal aquatic ecosystems physiology, functional traits, and health; (iii) snow and ice accumulation, melting, and albedo; (iv) active surface composition (eruptions, landslides, evolving landscapes, hazard risks); (v) effects of changing land use on surface energy, water, momentum, and carbon fluxes; and (vi) managing agriculture, natural habitats, water use/quality, and urban development. We review existing algorithms in the following categories: snow/ice, aquatic environments, geology, and terrestrial vegetation, and summarize the community-state-of-practice in each category. This effort synthesizes the findings of more than 130 scientists.
•The 2017 Decadal Survey recommended Surface Biology and Geology mission•Visible to shortwave infrared hyperspectral and multi-band thermal data•Global high resolution measurements at sub-monthly temporal resolution•Applications in snow/ice, aquatic environment, geology, and terrestrial vegetation•We review existing relevant algorithms and community-state-of-practice
Sea surface temperature anomalies in mid‐latitude north Pacific Ocean are compared with a cyclo‐stationary stochastic model in which the anomalies are forced by atmospheric “weather” disturbances. ...The results show that the model explains the observed two‐time auto‐covariances of the anomalies for almost all (98%) of the studied region.
The genus Salix (willows), with 33 species, represents the most diverse genus of woody plants in the European Alps. Many species dominate subalpine and alpine types of vegetation. Despite a long ...history of research on willows, the evolutionary and ecological factors for this species richness are poorly known. Here we will review recent progress in research on phylogenetic relationships, evolution, ecology, and speciation in alpine willows. Phylogenomic reconstructions suggest multiple colonization of the Alps, probably from the late Miocene onward, and reject hypotheses of a single radiation. Relatives occur in the Arctic and in temperate Eurasia. Most species are widespread in the European mountain systems or in the European lowlands. Within the Alps, species differ ecologically according to different elevational zones and habitat preferences. Homoploid hybridization is a frequent process in willows and happens mostly after climatic fluctuations and secondary contact. Breakdown of the ecological crossing barriers of species is followed by introgressive hybridization. Polyploidy is an important speciation mechanism, as 40% of species are polyploid, including the four endemic species of the Alps. Phylogenomic data suggest an allopolyploid origin for all taxa analyzed so far. Further studies are needed to specifically analyze biogeographical history, character evolution, and genome evolution of polyploids.
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