208 research outputs found
A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure-activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors
Measurement of airborne fission products in Chapel Hill, NC, USA from the Fukushima Dai-ichi reactor accident
We present measurements of airborne fission products in Chapel Hill, NC, USA,
from 62 days following the March 11, 2011, accident at the Fukushima Dai-ichi
nuclear power plant. Airborne particle samples were collected daily in air
filters and radio-assayed with two high-purity germanium (HPGe) detectors. The
fission products I-131 and Cs-137 were measured with maximum activities of 4.2
+/- 0.6 mBq/m^3 and 0.42 +/- 0.07 mBq/m^3 respectively. Additional activity
from I-131, I-132, Cs-134, Cs-136, Cs-137 and Te-132 were measured in the same
air filters using a low-background HPGe detector at the Kimballton Underground
Research Facility (KURF).Comment: 10 pages, 4 figure
Confined granular packings: structure, stress, and forces
The structure and stresses of static granular packs in cylindrical containers
are studied using large-scale discrete element molecular dynamics simulations
in three dimensions. We generate packings by both pouring and sedimentation and
examine how the final state depends on the method of construction. The vertical
stress becomes depth-independent for deep piles and we compare these stress
depth-profiles to the classical Janssen theory. The majority of the tangential
forces for particle-wall contacts are found to be close to the Coulomb failure
criterion, in agreement with the theory of Janssen, while particle-particle
contacts in the bulk are far from the Coulomb criterion. In addition, we show
that a linear hydrostatic-like region at the top of the packings unexplained by
the Janssen theory arises because most of the particle-wall tangential forces
in this region are far from the Coulomb yield criterion. The distributions of
particle-particle and particle-wall contact forces exhibit
exponential-like decay at large forces in agreement with previous studies.Comment: 11 pages, 11 figures, submitted to PRE (v2) added new references,
fixed typo
Studies of Dense Cores with ALMA
Dense cores are the simplest star-forming sites that we know, but despite
their simplicity, they still hold a number of mysteries that limit our
understanding of how solar-type stars form. ALMA promises to revolutionize our
knowledge of every stage in the life of a core, from the pre-stellar phase to
the final disruption by the newly born star. This contribution presents a brief
review of the evolution of dense cores and illustrates particular questions
that will greatly benefit from the increase in resolution and sensitivity
expected from ALMAComment: 6 pages, 2 figures, to appear in Astrophysics and Space Science,
special issue of "Science with ALMA: a new era for Astrophysics" conference,
ed. Dr. Bachille
Ideal cardiovascular health and inflammation in European adolescents: The HELENA study
Background and aims
Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents.
Methods and results
As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls.
Conclusion
Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention
Associations of autozygosity with a broad range of human phenotypes
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe
EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial
More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men
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