Summary
The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and ...man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper‐like ILCs with functional distinctions as seen by T‐helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology.
The earliest modern humans outside Africa Hershkovitz, Israel; Weber, Gerhard W; Quam, Rolf ...
Science (American Association for the Advancement of Science),
01/2018, Letnik:
359, Številka:
6374
Journal Article
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To date, the earliest modern human fossils found outside of Africa are dated to around 90,000 to 120,000 years ago at the Levantine sites of Skhul and Qafzeh. A maxilla and associated dentition ...recently discovered at Misliya Cave, Israel, was dated to 177,000 to 194,000 years ago, suggesting that members of the
clade left Africa earlier than previously thought. This finding changes our view on modern human dispersal and is consistent with recent genetic studies, which have posited the possibility of an earlier dispersal of
around 220,000 years ago. The Misliya maxilla is associated with full-fledged Levallois technology in the Levant, suggesting that the emergence of this technology is linked to the appearance of
in the region, as has been documented in Africa.
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed ...patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T
) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T
1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T
responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
Cardiac differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic gene regulatory networks during stepwise fate transitions but often generates immature cell types ...that do not fully recapitulate properties of their adult counterparts, suggesting incomplete activation of key transcriptional networks. We performed extensive single-cell transcriptomic analyses to map fate choices and gene expression programs during cardiac differentiation of hPSCs and identified strategies to improve in vitro cardiomyocyte differentiation. Utilizing genetic gain- and loss-of-function approaches, we found that hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation. This study therefore provides a key transcriptional roadmap of in vitro cardiac differentiation at single-cell resolution, revealing fundamental mechanisms underlying heart development and differentiation of hPSC-derived cardiomyocytes.
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•Single-cell RNA-seq during cardiac hPSC differentiation reveals cellular heterogeneity•A key cardiac regulatory gene, HOPX, is rarely expressed during in vitro differentiation•HOPX is a key in vitro regulator of cardiomyocyte hypertrophy and maturation
Friedman et al. performed single-cell transcriptional analysis over a time course of in vitro cardiac differentiation from human pluripotent stem cells. They utilized these data to identify the requirement of hypertrophic stimuli for expression of a cardiac regulatory gene, HOPX, to generate cardiomyocytes more accurately reflecting in vivo heart development.
Qafzeh Cave, the burial grounds of several anatomically modern humans, producers of Mousterian industry, yielded archaeological evidence reflecting their modern behavior. Dated to 92
ka
BP, the lower ...layers at the site contained a series of hearths, several human graves, flint artifacts, animal bones, a collection of sea shells, lumps of red ochre, and an incised cortical flake. The marine shells were recovered from layers earlier than most of the graves except for one burial. The shells were collected and brought from the Mediterranean Sea shore some 35
km away, and are complete
Glycymeris bivalves, naturally perforated. Several valves bear traces of having been strung, and a few had ochre stains on them.
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ...ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.
The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 ...acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300-1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.
We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g-2 Experiment for the positive muon magnetic anomaly a_{μ}≡(g_{μ}-2)/2. The anomaly is determined from the ...precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ω_{a} between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ωover ˜_{p}^{'} in a spherical water sample at 34.7 °C. The ratio ω_{a}/ωover ˜_{p}^{'}, together with known fundamental constants, determines a_{μ}(FNAL)=116 592 040(54)×10^{-11} (0.46 ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both μ^{+} and μ^{-}, the new experimental average of a_{μ}(Exp)=116 592 061(41)×10^{-11} (0.35 ppm) increases the tension between experiment and theory to 4.2 standard deviations.
BASS. XXII. The BASS DR2 AGN Catalog and Data Koss, Michael J.; Ricci, Claudio; Trakhtenbrot, Benny ...
The Astrophysical journal. Supplement series,
07/2022, Letnik:
261, Številka:
1
Journal Article
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Abstract We present the active galactic nucleus (AGN) catalog and optical spectroscopy for the second data release of the Swift BAT AGN Spectroscopic Survey (BASS DR2). With this DR2 release we ...provide 1449 optical spectra, of which 1182 are released for the first time, for the 858 hard-X-ray-selected AGNs in the Swift BAT 70-month sample. The majority of the spectra (801/1449, 55%) are newly obtained from Very Large Telescope (VLT)/X-shooter or Palomar/Doublespec. Many of the spectra have both higher resolution ( R > 2500, N ∼ 450) and/or very wide wavelength coverage (3200–10000 Å, N ∼ 600) that are important for a variety of AGN and host galaxy studies. We include newly revised AGN counterparts for the full sample and review important issues for population studies, with 47 AGN redshifts determined for the first time and 790 black hole mass and accretion rate estimates. This release is spectroscopically complete for all AGNs (100%, 858/858), with 99.8% having redshift measurements (857/858) and 96% completion in black hole mass estimates of unbeamed AGNs (722/752). This AGN sample represents a unique census of the brightest hard-X-ray-selected AGNs in the sky, spanning many orders of magnitude in Eddington ratio ( L / L Edd = 10 −5 –100), black hole mass ( M BH = 10 5 –10 10 M ⊙ ), and AGN bolometric luminosity ( L bol = 10 40 –10 47 erg s −1 ).
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