Excessive adipose tissue macrophage accumulation in obesity has been implicated in mediating inflammatory responses that impair glucose homeostasis and promote insulin resistance. Colony-stimulating ...factor 1 (CSF1) controls macrophage differentiation, and here we sought to determine the effect of a CSF1 receptor inhibitor, PLX3397, on adipose tissue macrophage levels and understand the impact on glucose homeostasis in mice.
A Ten-week-old mice were fed a chow or high-fat diet for 10 weeks and then treated with PLX3397 via oral gavage (50 mg/kg) every second day for 3 weeks, with subsequent monitoring of glucose tolerance, insulin sensitivity and assessment of adipose tissue immune cells.
PLX3397 treatment substantially reduced macrophage numbers in adipose tissue of both chow and high-fat diet fed mice without affecting total myeloid cell levels. Despite this, PLX3397 did not greatly alter glucose homeostasis, did not affect high-fat diet-induced increases in visceral fat cytokine expression (Il-6 and Tnfa) and had limited effect on the phosphorylation of the stress kinases JNK and ERK and macrophage polarization.
Our results indicate that macrophage infiltration of adipose tissue induced by a high-fat diet may not be the trigger for impairments in whole body glucose homeostasis, and that anti-CSF1 therapies are not likely to be useful as treatments for insulin resistance.
ABSTRACT
Determining the distribution of redshifts of galaxies observed by wide-field photometric experiments like the Dark Energy Survey (DES) is an essential component to mapping the matter density ...field with gravitational lensing. In this work we describe the methods used to assign individual weak lensing source galaxies from the DES Year 3 Weak Lensing Source Catalogue to four tomographic bins and to estimate the redshift distributions in these bins. As the first application of these methods to data, we validate that the assumptions made apply to the DES Y3 weak lensing source galaxies and develop a full treatment of systematic uncertainties. Our method consists of combining information from three independent likelihood functions: self-organizing map p(z) (sompz), a method for constraining redshifts from galaxy photometry; clustering redshifts (WZ), constraints on redshifts from cross-correlations of galaxy density functions; and shear ratios (SRs), which provide constraints on redshifts from the ratios of the galaxy-shear correlation functions at small scales. Finally, we describe how these independent probes are combined to yield an ensemble of redshift distributions encapsulating our full uncertainty. We calibrate redshifts with combined effective uncertainties of σ〈z〉 ∼ 0.01 on the mean redshift in each tomographic bin.
Abstract
We describe the Dark Energy Survey (DES) photometric data set assembled from the first three years of science operations to support DES Year 3 cosmologic analyses, and provide usage notes ...aimed at the broad astrophysics community.
Y3
GOLD
improves on previous releases from DES,
Y1
GOLD
, and Data Release 1 (DES DR1), presenting an expanded and curated data set that incorporates algorithmic developments in image detrending and processing, photometric calibration, and object classification.
Y3
GOLD
comprises nearly 5000 deg
2
of
grizY
imaging in the south Galactic cap, including nearly 390 million objects, with depth reaching a signal-to-noise ratio ∼10 for extended objects up to
i
AB
∼ 23.0, and top-of-the-atmosphere photometric uniformity <3 mmag. Compared to DR1, photometric residuals with respect to Gaia are reduced by 50%, and per-object chromatic corrections are introduced.
Y3
GOLD
augments DES DR1 with simultaneous fits to multi-epoch photometry for more robust galactic color measurements and corresponding photometric redshift estimates.
Y3
GOLD
features improved morphological star–galaxy classification with efficiency >98% and purity >99% for galaxies with 19 <
i
AB
< 22.5. Additionally, it includes per-object quality information, and accompanying maps of the footprint coverage, masked regions, imaging depth, survey conditions, and astrophysical foregrounds that are used to select the cosmologic analysis samples.
We constrain cosmological parameters and galaxy-bias parameters using the combination of galaxy clustering and galaxy-galaxy lensing measurements from the Dark Energy Survey (DES) year-3 data. We ...describe our modeling framework and choice of scales analyzed, validating their robustness to theoretical uncertainties in small-scale clustering by analyzing simulated data. Using a linear galaxy-bias model and redMaGiC galaxy sample, we obtain 10% constraints on the matter density of the Universe. We also implement a nonlinear galaxy-bias model to probe smaller scales that includes parametrization based on hybrid perturbation theory and find that it leads to a 17% gain in cosmological constraining power. We perform robustness tests of our methodology pipeline and demonstrate stability of the constraints to changes in the theory model. Using the redMaGiC galaxy sample as foreground lens galaxies and adopting the best-fitting cosmological parameters from DES year-1 data, we find the galaxy clustering and galaxy-galaxy lensing measurements to exhibit significant signals akin to decorrelation between galaxies and mass on large scales, which is not expected in any current models. This likely systematic measurement error biases our constraints on galaxy bias and the S8 parameter. We find that a scale-, redshift- and sky-area-independent phenomenological decorrelation parameter can effectively capture this inconsistency between the galaxy clustering and galaxy-galaxy lensing. We trace the source of this correlation to a color-dependent photometric issue and minimize its impact on our result by changing the selection criteria of redMaGiC galaxies. Using this new sample, our constraints on the S8 parameter are consistent with previous studies and we find a small shift in the Ωm constraints compared to the fiducial redMaGiC sample. We infer the constraints on the mean host-halo mass of the redMaGiC galaxies in this new sample from the large-scale bias constraints, finding the galaxies occupy halos of mass approximately 1.6×1013 M⊙/h.
COVID-19 has had a calamitous effect on the global community. Despite intense study, the immunologic response to the infection is only partially understood. In addition to older age and ethnicity, ...patients with comorbidities including obesity, diabetes, hypertension, coronary artery disease, malignancy, renal, and pulmonary disease may experience severe outcomes. Some patients with primary immunodeficiency (PID) and secondary immunodeficiency also appear to be at increased risk from COVID-19. In addition to vulnerability to SARS-CoV-2, patients with PIDs often have chronic pulmonary disease and may not respond to vaccines, which exacerbates their long-term risk. Patients with common variable immunodeficiency disorders, the most frequent symptomatic PID in adults and children, have a spectrum of B- and T-cell defects. It may be possible to stratify their risk for severe COVID-19 based on age, ethnicity, the severity of the T-cell defect, and the presence of other comorbidities. Patients with common variable immunodeficiency disorders and other immunodeficiencies are at risk for Chronic COVID-19, a dangerous stalemate between a suboptimal immune response and SARS-CoV-2. Intra-host viral evolution could result in the rapid emergence of vaccine-resistant mutants and variants of high consequence; it is a public health emergency. Vaccination and prevention of Chronic COVID-19 in immunodeficient patients is therefore of the utmost priority. Having a reliable diagnostic assay for T-cell immunity to SARS-CoV-2 is critical for evaluating responses to vaccines in these patients. New treatments for SARS-CoV-2 such as NZACE2-Pātari are likely to be particularly beneficial for immunodeficient patients, especially those who fail to mount a robust T-cell response to COVID-19 vaccines.
We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by ...optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.
Trichomoniasis, a prevalent sexually transmitted infection, is commonly symptomatic in women. The causative agent is
, an extracellular protozoan parasite. The host-protective mechanisms and ...molecules of vaginal lactobacilli that counteract this pathogen are largely unknown. This study examines the inhibition promoted by
against the adhesion of
to host cells, a critical virulence aspect of this pathogen. We observed that the vaginal strain
ATCC 9857 is highly inhibitory by various contact-dependent mechanisms and that surface proteins are largely responsible for this inhibitory phenotype. We found that the aggregation-promoting factor APF-2 from these bacteria significantly contributes to inhibition of the adhesion of
to human vaginal ectocervical cells. Understanding the molecules and mechanisms used by lactobacilli to protect the host against
might help in the development of novel and specific therapeutic strategies that take advantage of the natural microbiota.
A radical lipidation: Application of a novel thiol–ene lipidation enables the one‐step synthesis of self‐adjuvanting antigenic peptides as vaccine candidates. The resultant monoacyl lipopeptides are ...shown to activate monocytes in a robust manner.
ABSTRACT
The Cold Spot is a puzzling large-scale feature in the Cosmic Microwave Background temperature maps and its origin has been subject to active debate. As an important foreground structure at ...low redshift, the Eridanus supervoid was recently detected, but it was subsequently determined that, assuming the standard ΛCDM model, only about 10–20 per cent of the observed temperature depression can be accounted for via its Integrated Sachs–Wolfe imprint. However, R ≳ 100 h−1Mpc supervoids elsewhere in the sky have shown ISW imprints AISW ≈ 5.2 ± 1.6 times stronger than expected from ΛCDM (AISW = 1), which warrants further inspection. Using the Year-3 redMaGiC catalogue of luminous red galaxies from the Dark Energy Survey, here we confirm the detection of the Eridanus supervoid as a significant underdensity in the Cold Spot’s direction at z < 0.2. We also show, with S/N ≳ 5 significance, that the Eridanus supervoid appears as the most prominent large-scale underdensity in the dark matter mass maps that we reconstructed from DES Year-3 gravitational lensing data. While we report no significant anomalies, an interesting aspect is that the amplitude of the lensing signal from the Eridanus supervoid at the Cold Spot centre is about 30 per cent lower than expected from similar peaks found in N-body simulations based on the standard ΛCDM model with parameters Ωm = 0.279 and σ8 = 0.82. Overall, our results confirm the causal relation between these individually rare structures in the cosmic web and in the CMB, motivating more detailed future surveys in the Cold Spot region.
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