Attenuated effector T cells are linked to control of chronic HBV infection.

Hepatitis B virus (HBV)-specific CD8 T cells play a dominant role during acute-resolving HBV infection but are functionally impaired during chronic HBV infection in humans. These functional deficits have been linked with metabolic and phenotypic heterogeneity, but it has remained unclear to what extent different subsets of HBV-specific CD8 T cells still suppress viral replication. We addressed this issue by deep profiling, functional testing and perturbation of HBV-specific CD8 T cells during different phases of chronic HBV infection.

Peptide-Loaded HLA Class I Tetramer-Associated Magnetic Bead-Based Enrichment of HBV-Specific CD8+ T Cells.

HBV-specific CD8+ T cells are only present at the low frequency during chronic infection. Thus, they are often undetectable by conventional ex vivo staining methods using peptide-loaded HLA class I tetramers. Detection sensitivity can be increased by magnetic bead-based enrichment strategies following staining with peptide-loaded HLA class I tetramers.

Bioaccessibility of Metallic Nickel and Nickel Oxide Nanoparticles in Four Simulated Biological Fluids.

Bioaccessibility of metals from substances and alloys is increasingly used as part of the assessment to predict potential toxicity. However, data are sparse on the metal bioaccessibility from nanoparticle (NP) size metal substances. This study examines nickel ion release from metallic nickel and nickel oxide micron particles (MPs) and NPs in simulated biological fluids at various timepoints including those relevant for specific routes of exposure.

Unraveling the Np(V) sorption on ZrO: A batch, spectroscopic and modeling combined approach.

The interactions of the long-lived actinide neptunium with the corrosion product zirconia (ZrO) have to be considered in the safety assessment of a repository for radioactive waste. The sorption of Np(V) on ZrO was investigated in the absence of carbonate at the macroscopic and molecular scale. At the macroscopic level, the Np(V) uptake was independent of ionic strength and the isoelectric point of the pristine zirconia was increased, both suggesting the presence of inner-sphere Np(V) surface complexes.

Post-treatment haemolysis is common following oral artemisinin combination therapy of uncomplicated malaria in travellers.

Background: Artemisinin-based combination therapy (ACT) for the treatment of malaria is highly effective, well tolerated and safe. Episodes of delayed haemolysis occur in up to 57.9% of patients with severe malaria treated with intravenous artesunate, mainly caused by 'pitting' of infected red blood cells in the spleen and the delayed loss of these once-infected RBCs (oiRBCs).

Impact of dietary vitamin D on immunoregulation and disease pathology in lupus-prone NZB/W F1 mice.

Vitamin D (VD) deficiency is a highly prevalent worldwide phenomenon and is extensively discussed as a risk factor for the development of systemic lupus erythematosus (SLE) and other immune-mediated diseases. In addition, it is now appreciated that VD possesses multiple immunomodulatory effects. This study aims to explore the impact of dietary VD intake on lupus manifestation and pathology in lupus-prone NZB/W F1 mice and identify the underlying immunological mechanisms modulated by VD.

Preparing for patients with high-consequence infectious diseases: Example of a high-level isolation unit.

Introduction: Patients with high-consequence infectious diseases (HCID) are rare in Western Europe. However, high-level isolation units (HLIU) must always be prepared for patient admission. Case fatality rates of HCID can be reduced by providing optimal intensive care management.

Neoantigens as potential vaccines in hepatocellular carcinoma.

Background: Neoantigens, new immunogenic sequences arising from tumor mutations, have been associated with response to immunotherapy and are considered potential targets for vaccination. Hepatocellular carcinoma (HCC) is a moderately mutated tumor, where the neoantigen repertoire has not been investigated. Our aim was to analyze whether tumors in HCC patients contain immunogenic neoantigens suitable for future use in therapeutic vaccination.

Complexation of Np(V) with the Dicarboxylates, Malonate, and Succinate: Complex Stoichiometry, Thermodynamic Data, and Structural Information.

The complexation of Np(V) with malonate and succinate is studied by different spectroscopic techniques, namely, attenuated total reflection Fourier transform infrared (ATR FT-IR) and extended X-ray absorption fine-structure (EXAFS) spectroscopy, as well as by quantum chemistry to determine the speciation, thermodynamic data, and structural information of the formed complexes. For complex stoichiometries and the thermodynamic functions (log β(Θ), ΔH, ΔS), near infrared absorption spectroscopy (vis/NIR) is applied. The complexation reactions are investigated as a function of the total concentration of malonate ([Mal]) and succinate ([Succ]), ionic strength [ = 0.

Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a global health burden with increasing incidence, poor prognosis and limited therapeutic options. Natural killer (NK) cells exhibit potent anti-tumoral activity and therefore represent potential targets for immunotherapeutic approaches in HCC treatment. However, the anti-tumoral activity of NK cells in HCC associated with different etiologies, and the impact of the heterogeneous NK cell subset, e.

Heart failure with preserved ejection fraction according to the HFA-PEFF score in COVID-19 patients: clinical correlates and echocardiographic findings.

Aims: Viral-induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)-like syndromes. COVID-19 can lead to myocardial damage and vascular injury. We hypothesised that COVID-19 patients frequently develop a HFpEF-like syndrome, and designed this study to explore this.

CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity.

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection.

Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion.

Human cytomegalovirus (HCMV) causes congenital disease with long-term morbidity. HCMV glycoprotein B (gB) transitions irreversibly from a metastable prefusion to a stable postfusion conformation to fuse the viral envelope with a host cell membrane during entry. We stabilized prefusion gB on the virion with a fusion inhibitor and a chemical cross-linker, extracted and purified it, and then determined its structure to 3.

A comparison of subadult skeletal and dental development based on living and deceased samples.

Objectives: A fundamental assumption in biological anthropology is that living individuals will present with different growth than non-survivors of the same population. The aim is to address the question of whether growth and development data of non-survivors are reflective of the biological consequences of selective mortality and/or stress.

Materials And Methods: The study compares dental development and skeletal growth collected from radiographic images of contemporary samples of living and deceased individuals from the United States (birth to 20 years) and South Africa (birth to 12 years).

TOX defines the degree of CD8+ T cell dysfunction in distinct phases of chronic HBV infection.

Objective: Chronic hepatitis B virus (HBV) infection is characterised by HBV-specific CD8+ T cell dysfunction that has been linked to Tcell exhaustion, a distinct differentiation programme associated with persisting antigen recognition. Recently, Thymocyte Selection-Associated High Mobility Group Box (TOX) was identified as master regulator of CD8+ T cell exhaustion. Here, we addressed the role of TOX in HBV-specific CD8+ T cell dysfunction associated with different clinical phases of infection.

SARS-CoV-2-specific T cell responses and correlations with COVID-19 patient predisposition.

Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So far, viral targets of cellular immunity and factors determining successful mounting of T cell responses are poorly defined. We therefore analyzed cellular responses to membrane, nucleocapsid, and spike proteins in individuals suffering from moderate or severe infection and in individuals who recovered from mild disease.

Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time.

Gene-Dose Effect of Gain-of-Function Mutations Determines Neutrophil Activation in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is caused by mutations within the Mediterranean fever () gene. Disease severity depends on genotype and gene dose with most serious clinical courses observed in patients with M694V homozygosity. Neutrophils are thought to play an important role in the initiation and perpetuation of inflammatory processes in FMF, but little is known about the specific characteristics of these cells in FMF patients.

Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19).

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions.

Methods: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin.

Bioaccessibility of nickel and cobalt in synthetic gastric and lung fluids and its potential use in alloy classification.

This study investigated nickel and cobalt ion release from the metals and several alloys in synthetic gastric, as well as interstitial and lysosomal lung fluids. Results were used to calculate the relative bioaccessible concentrations (RBCs) of the metals. Nickel release from SS 316L powder in gastric fluid was >300-fold lower than from a simple mixture of powders of the same bulk composition.

Heterogeneity of HBV-Specific CD8 T-Cell Failure: Implications for Immunotherapy.

Chronic hepatitis B virus (HBV) infection is a major global health burden affecting around 257 million people worldwide. The consequences of chronic HBV infection include progressive liver damage, liver cirrhosis, and hepatocellular carcinoma. Although current direct antiviral therapies successfully lead to suppression of viral replication and deceleration of liver cirrhosis progression, these treatments are rarely curative and patients often require a life-long therapy.

Complex formation between UO and α-isosaccharinic acid: insights on a molecular level.

Cellulosic materials present as tissue, paper, wood, or filter materials in low and intermediate level waste will degrade under alkaline conditions if water ingresses in a cementitious backfilled repository. The main degradation product is isosaccharinic acid. Complex formation with isosaccharinic acid may adversely affect the retention of radionuclides by the sorption or formation of solid phases.