Serum amyloid A inhibits RANKL-induced osteoclast formation

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.open

Out of Their Depth? Isolated Deep Populations of the Cosmopolitan Coral Desmophyllum dianthus May Be Highly Vulnerable to Environmental Change

Deep sea scleractinian corals will be particularly vulnerable to the effects of climate change, facing loss of up to 70% of their habitat as the Aragonite Saturation Horizon (below which corals are unable to form calcium carbonate skeletons) rises. Persistence of deep sea scleractinian corals will therefore rely on the ability of larvae to disperse to, and colonise, suitable shallow-water habitat. We used DNA sequence data of the internal transcribed spacer (ITS), the mitochondrial ribosomal subunit (16S) and mitochondrial control region (MtC) to determine levels of gene flow both within and among populations of the deep sea coral Desmophyllum dianthus in SE Australia, New Zealand and Chile to assess the ability of corals to disperse into different regions and habitats. We found significant genetic subdivision among the three widely separated geographic regions consistent with isolation and limited contemporary gene flow. Furthermore, corals from different depth strata (shallow <600 m, mid 1000–1500 m, deep >1500 m) even on the same or nearby seamounts were strongly differentiated, indicating limited vertical larval dispersal. Genetic differentiation with depth is consistent with the stratification of the Subantarctic Mode Water, Antarctic Intermediate Water, the Circumpolar Deep and North Pacific Deep Waters in the Southern Ocean, and we propose that coral larvae will be retained within, and rarely migrate among, these water masses. The apparent absence of vertical larval dispersal suggests deep populations of D. dianthus are unlikely to colonise shallow water as the aragonite saturation horizon rises and deep waters become uninhabitable. Similarly, assumptions that deep populations will act as refuges for shallow populations that are impacted by activities such as fishing or mining are also unlikely to hold true. Clearly future environmental management strategies must consider both regional and depth-related isolation of deep-sea coral populations

The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi

<p>Abstract</p> <p>Background</p> <p>Chronic chagasic cardiomyopathy is a debilitating and frequently fatal outcome of human infection with the protozoan parasite, <it>Trypanosoma cruzi</it>. Microarray analysis of gene expression during the <it>T. cruzi </it>life-cycle could be a valuable means of identifying drug and vaccine targets based on their appropriate expression patterns, but results from previous microarray studies in <it>T. cruzi </it>and related kinetoplastid parasites have suggested that the transcript abundances of most genes in these organisms do not vary significantly between life-cycle stages.</p> <p>Results</p> <p>In this study, we used whole genome, oligonucleotide microarrays to globally determine the extent to which <it>T. cruzi </it>regulates mRNA relative abundances over the course of its complete life-cycle. In contrast to previous microarray studies in kinetoplastids, we observed that relative transcript abundances for over 50% of the genes detected on the <it>T. cruzi </it>microarrays were significantly regulated during the <it>T. cruzi </it>life-cycle. The significant regulation of 25 of these genes was confirmed by quantitative reverse-transcriptase PCR (qRT-PCR). The <it>T. cruzi </it>transcriptome also mirrored published protein expression data for several functional groups. Among the differentially regulated genes were members of paralog clusters, nearly 10% of which showed divergent expression patterns between cluster members.</p> <p>Conclusion</p> <p>Taken together, these data support the conclusion that transcript abundance is an important level of gene expression regulation in <it>T. cruzi</it>. Thus, microarray analysis is a valuable screening tool for identifying stage-regulated <it>T. cruzi </it>genes and metabolic pathways.</p

Chagas Cardiomyopathy Manifestations and Trypanosoma cruzi Genotypes Circulating in Chronic Chagasic Patients

Chagas disease caused by Trypanosoma cruzi is a complex disease that is endemic and an important problem in public health in Latin America. The T. cruzi parasite is classified into six discrete taxonomic units (DTUs) based on the recently proposed nomenclature (TcI, TcII, TcIII, TcIV, TcV and TcVI). The discovery of genetic variability within TcI showed the presence of five genotypes (Ia, Ib, Ic, Id and Ie) related to the transmission cycle of Chagas disease. In Colombia, TcI is more prevalent but TcII has also been reported, as has mixed infection by both TcI and TcII in the same Chagasic patient. The objectives of this study were to determine the T. cruzi DTUs that are circulating in Colombian chronic Chagasic patients and to obtain more information about the molecular epidemiology of Chagas disease in Colombia. We also assessed the presence of electrocardiographic, radiologic and echocardiographic abnormalities with the purpose of correlating T. cruzi genetic variability and cardiac disease. Molecular characterization was performed in Colombian adult chronic Chagasic patients based on the intergenic region of the mini-exon gene, the 24Sα and 18S regions of rDNA and the variable region of satellite DNA, whereby the presence of T.cruzi I, II, III and IV was detected. In our population, mixed infections also occurred, with TcI-TcII, TcI-TcIII and TcI-TcIV, as well as the existence of the TcI genotypes showing the presence of genotypes Ia and Id. Patients infected with TcI demonstrated a higher prevalence of cardiac alterations than those infected with TcII. These results corroborate the predominance of TcI in Colombia and show the first report of TcIII and TcIV in Colombian Chagasic patients. Findings also indicate that Chagas cardiomyopathy manifestations are more correlated with TcI than with TcII in Colombia

Dark Energy Survey Year 3 results: Constraints on extensions to ΛcDM with weak lensing and galaxy clustering

We constrain six possible extensions to the Λ cold dark matter (CDM) model using measurements from the Dark Energy Survey's first three years of observations, alone and in combination with external cosmological probes. The DES data are the two-point correlation functions of weak gravitational lensing, galaxy clustering, and their cross-correlation. We use simulated data vectors and blind analyses of real data to validate the robustness of our results to astrophysical and modeling systematic errors. In many cases, constraining power is limited by the absence of theoretical predictions beyond the linear regime that are reliable at our required precision. The ΛCDM extensions are dark energy with a time-dependent equation of state, nonzero spatial curvature, additional relativistic degrees of freedom, sterile neutrinos with eV-scale mass, modifications of gravitational physics, and a binned σ8(z) model which serves as a phenomenological probe of structure growth. For the time-varying dark energy equation of state evaluated at the pivot redshift we find (wp,wa)=(-0.99-0.17+0.28,-0.9±1.2) at 68% confidence with zp=0.24 from the DES measurements alone, and (wp,wa)=(-1.03-0.03+0.04,-0.4-0.3+0.4) with zp=0.21 for the combination of all data considered. Curvature constraints of ωk=0.0009±0.0017 and effective relativistic species Neff=3.10-0.16+0.15 are dominated by external data, though adding DES information to external low-redshift probes tightens the ωk constraints that can be made without cosmic microwave background observables by 20%. For massive sterile neutrinos, DES combined with external data improves the upper bound on the mass meff by a factor of 3 compared to previous analyses, giving 95% limits of (ΔNeff,meff)≤(0.28,0.20 eV) when using priors matching a comparable Planck analysis. For modified gravity, we constrain changes to the lensing and Poisson equations controlled by functions ς(k,z)=ς0ωΛ(z)/ωΛ,0 and μ(k,z)=μ0ωΛ(z)/ωΛ,0, respectively, to ς0=0.6-0.5+0.4 from DES alone and (ς0,μ0)=(0.04±0.05,0.08-0.19+0.21) for the combination of all data, both at 68% confidence. Overall, we find no significant evidence for physics beyond ΛCDM

Search for CP violating top quark couplings in pp collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2205.07434v2 [hep-ex], https://arxiv.org/abs/2205.07434. It has not been certified by peer review.Results are presented from a search for CP violation in top quark pair production, using proton-proton collisions at a center-of-mass energy of 13 TeV. The data used for this analysis consist of final states with two charged leptons collected by the CMS experiment, and correspond to an integrated luminosity of 35.9 fb−1. The search uses two observables, O1 and O3, which are Lorentz scalars. The observable O1 is constructed from the four-momenta of the charged leptons and the reconstructed top quarks, while O3 consists of the four-momenta of the charged leptons and the b quarks originating from the top quarks. Asymmetries in these observables are sensitive to CP violation, and their measurement is used to determine the chromoelectric dipole moment of the top quark. The results are consistent with the expectation from the standard model. [Figure not available: see fulltext.].SCOAP

Search for nonresonant Higgs boson pair production in the four leptons plus two b jets final state in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.10657v2 [hep-ex], https://arxiv.org/abs/2206.10657 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at this http URL (CMS Public Pages). Report number: CMS-HIG-20-004, CERN-EP-2022-114.The first search for nonresonant production of Higgs boson pairs (HH) with one H decaying into four leptons and the other into a pair of b quarks is presented, using proton-proton collisions recorded at a center-of-mass energy of s = 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 138 fb−1. A 95% confidence level upper limit of 32.4 is set on the signal strength modifier μ, defined as the ratio of the observed HH production rate in the HH→ ZZ∗b b ¯ → 4 ℓb b ¯ decay channel to the standard model (SM) expectation. Possible modifications of the H trilinear coupling λ HHH with respect to the SM value are investigated. The coupling modifier κλ, defined as λ HHH divided by its SM prediction, is constrained to be within the observed (expected) range −8.8 (−9.8) < κλ < 13.4 (15.0) at 95% confidence level. [Figure not available: see fulltext.].SCOAP3

Search for long-lived particles decaying to a pair of muons in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2205.08582v2 [hep-ex], https://arxiv.org/abs/2205.08582 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures and tables, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-006 (CMS Public Pages).An inclusive search for long-lived exotic particles decaying to a pair of muons is presented. The search uses data collected by the CMS experiment at the CERN LHC in proton-proton collisions at s = 13 TeV in 2016 and 2018 and corresponding to an integrated luminosity of 97.6 fb−1. The experimental signature is a pair of oppositely charged muons originating from a common secondary vertex spatially separated from the pp interaction point by distances ranging from several hundred μm to several meters. The results are interpreted in the frameworks of the hidden Abelian Higgs model, in which the Higgs boson decays to a pair of long-lived dark photons ZD, and of a simplified model, in which long-lived particles are produced in decays of an exotic heavy neutral scalar boson. For the hidden Abelian Higgs model with m(ZD) greater than 20 GeV and less than half the mass of the Higgs boson, they provide the best limits to date on the branching fraction of the Higgs boson to dark photons for cτ(ZD) (varying with m(ZD)) between 0.03 and ≈0.5 mm, and above ≈0.5 m. Our results also yield the best constraints on long-lived particles with masses larger than 10 GeV produced in decays of an exotic scalar boson heavier than the Higgs boson and decaying to a pair of muons. [Figure not available: see fulltext.].SCOAP3

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2301.08096v2 [hep-ex], https://arxiv.org/abs/2301.08096 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-003 (CMS Public Pages).A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (t ~1), is presented. The search targets the four-body decay of the t ~1 , which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (χ~10), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(t ~1) and m(χ~10). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(t ~1) − m(χ~10) = 10 and 80 GeV, respectively. [Figure not available: see fulltext.].SCOAP3

Dark Energy Survey Year 3 Results: Cosmology from Cosmic Shear and Robustness to Modeling Uncertainty

This work and its companion paper, Amon et al. [Phys. Rev. D 105, 023514 (2022)], present cosmic shear measurements and cosmological constraints from over 100 million source galaxies in the Dark Energy Survey (DES) Year 3 data. We constrain the lensing amplitude parameter S 8 ≡ σ 8 √ Ω m / 0.3 at the 3% level in Λ CDM : S 8 = 0.75 9 + 0.025 − 0.023 (68% CL). Our constraint is at the 2% level when using angular scale cuts that are optimized for the Λ CDM analysis: S 8 = 0.77 2 + 0.018 − 0.017 (68% CL). With cosmic shear alone, we find no statistically significant constraint on the dark energy equation-of-state parameter at our present statistical power. We carry out our analysis blind, and compare our measurement with constraints from two other contemporary weak lensing experiments: the Kilo-Degree Survey (KiDS) and Hyper-Suprime Camera Subaru Strategic Program (HSC). We additionally quantify the agreement between our data and external constraints from the Cosmic Microwave Background (CMB). Our DES Y3 result under the assumption of Λ CDM is found to be in statistical agreement with Planck 2018, although favors a lower S 8 than the CMB-inferred value by 2.3 σ (a p -value of 0.02). This paper explores the robustness of these cosmic shear results to modeling of intrinsic alignments, the matter power spectrum and baryonic physics. We additionally explore the statistical preference of our data for intrinsic alignment models of different complexity. The fiducial cosmic shear model is tested using synthetic data, and we report no biases greater than 0.3 σ in the plane of S 8 × Ω m caused by uncertainties in the theoretical models