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Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a nove

Prediction of High Nodal Burden in Patients With Sentinel Node-Positive Luminal ERBB2-Negative Breast Cancer

IMPORTANCE: In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment.OBJECTIVE: To develop a

Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se

Immunization with heat-killed Mycobacterium bovis bacille Calmette-Guerin (BCG) in Eurocine L3 adjuvant protects against tuberculosis

The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromised subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) chall

The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1 + precursors.

The intestinal lamina propria contains a diverse network of fibroblasts that provide key support functions to cells within their local environment. Despite this, our understanding of the diversity, location and ontogeny of fibroblasts within and along the length of the intestine remains incomplete. Here we show that the small and large intestinal lamina propria contain similar fibroblast subsets t

Boosted production of antibodies which neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following mRNA vaccination - a case study

Vaccinated convalescents do not develop severe COVID-19 after infection with new SARS-CoV-2 variants. We questioned how mRNA vaccination of convalescents provides protection from emerging virus variant. From the cohort of 71 convalescent plasma donors, we identified a patient who developed immune response to infection with SARS-CoV-2 variant of 20A clade and who subsequently received mRNA vaccine

Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis

Background: Dysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the abi

The Cherenkov Telescope Array: layout, design and performance

The Cherenkov Telescope Array (CTA) will be the next generation very-high-energy gamma-ray observatory. CTA is expected to provide substantial improvement in accuracy and sensitivity with respect to existing instruments thanks to a tenfold increase in the number of telescopes and their state-of-the-art design. Detailed Monte Carlo simulations are used to further optimise the number of telescopes a

The crystal structure of human adenylate kinase 6 : An adenylate kinase localized to the cell nucleus

Adenylate kinases (AKs) play important roles in nucleotide metabolism in all organisms and in cellular energetics by means of phosphotransfer networks in eukaryotes. The crystal structure of a human AK named AK6 was determined by in-house sulfur single-wavelength anomalous dispersion phasing methods and refined to 2.0-A resolution with a free R factor of 21.8%. Sequence analyses revealed that huma

Enhanced expression of iNOS intratumorally and at the immunization site after immunization with IFNgamma-secreting rat glioma cells

Nitric oxide (NO) can modulate both tumor growth and antitumor immune responses. In order to elucidate the mechanism of curative therapeutic immunization with IFNgamma-producing glioma cells, we examined the expression of inducible nitric oxide synthase (iNOS) in tissue sections from immunized animals. There was a significantly enhanced iNOS expression both intratumorally and at the immunization s

Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus

Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%

Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.

OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential ro

Providing flexibility in a convolutional encoder

In future radio systems, flexible coding and decoding architectures will be required. In case of the latter, implementing architectural flexibility with regard to low power issues is a challenging task. The flexible encoding platform in this paper is a first step toward this envisioned decoder. It generates a wide class of codes, starting with convolutional codes. As an extension to this, turbo co

Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both inn

Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8(+) T cells (i.e., tumor or unrelated virus-spe

Synthesis and characterization of cobalt silicide films on silicon

Cobalt silicide has emerged as a leading contact material in silicon technology due to its low resistivity, high stability and small lattice mismatch. In this study, 0.2-0.4 mu m thick Co films were deposited on Si(100) wafers by RF magnetron sputtering at room temperature, and annealed at temperatures from 600 to 900 degrees C in vacuum. As-deposited and annealed samples were characterized by Rut

Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons

Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We r

Series summation of fractal fluctuations in electron billiard arrays

We fabricate a single billiard, a double billiard array, and a triple billiard array by etching a GaInAs/InP heterostructure, and perform a fractal analysis of the low-temperature magneto-conductance fluctuations measured in the billiards to facilitate an empirical study of how fractals combine in a physical system. We compare our results to simulated fractal traces, and find for both experiment a

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjogren's syndrome and hepatitis C in Swedish patients

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjogren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmo University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (accor