Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis.

Macrophage-to-foam cell transition is an integral part of atherosclerotic plaque progression. Particularly, oxidized low-density lipoprotein (oxLDL) is a driving factor in foam cell formation, altering macrophage function and metabolism. The aim of our research was to understand the impact of oxLDL-induced mitochondrial reactive oxygen species on macrophage-to-foam cell differentiation.

CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.

Mechanical forces acting on ligand-engaged T-cell receptors (TCR) have previously been implicated in T-cell antigen recognition and ligand discrimination, yet their magnitude, frequency, and impact remain unclear. Here, we quantitatively assess forces across various TCR:pMHC pairs with different bond lifetimes at single-molecule resolution, both before and during T-cell activation, on platforms that either include or exclude tangential force registration. For this purpose, we use glass-supported lipid bilayers presenting pMHC conjugated to a molecular force sensor unit at its base, adhesion factors and costimulatory molecules to the approaching T-cells.

IL-2 Complex Therapy Mitigates Humoral Rejection of Fully Mismatched Skin Allografts by Inhibiting IgG Alloantibody Formation.

Antibody-mediated rejection (ABMR) caused by donor-specific Abs (DSAs) is still the leading cause of late graft loss following clinical organ transplantation, and effective strategies to combat ABMR are still elusive. We previously showed that rIL-2 complexed with anti-IL-2 mAb clone JES6-1A12 (IL-2 cplx) leads to the selective expansion of regulatory T cells (Tregs) and the prolonged survival of MHC-mismatched skin allografts. Although the grafts were eventually rejected, mice failed to develop DSAs.

Molecular features of TNBC govern heterogeneity in the response to radiation and autophagy inhibition.

Triple negative breast cancer (TNBC) is a heterogeneous and a highly aggressive type of breast cancer. Standard of care for TNBC patients includes surgery, radio-, chemo- and immunotherapy, depending on the stage of the disease. Immunotherapy is ineffective as monotherapy but can be enhanced with taxane chemotherapy or radiotherapy.

Molecular Typing of Tick-Borne Pathogens in Ixodids of Bosnia and Herzegovina.

Ticks are key vectors of zoonotic pathogens, and their expanding distribution in Europe heightens public health concerns. In Bosnia and Herzegovina, while tick distribution is well documented, molecular data on tick-borne pathogens remain limited. This study aimed to illustrate the presence and diversity of these pathogens, focusing on areas with high human activity.

Epidemic-induced local awareness behavior inferred from surveys and genetic sequence data.

Behavior-disease models suggest that pandemics can be contained cost-effectively if individuals take preventive actions when disease prevalence rises among their close contacts. However, assessing local awareness behavior in real-world datasets remains a challenge. Through the analysis of mutation patterns in clinical genetic sequence data, we propose an efficient approach to quantify the impact of local awareness by identifying superspreading events and assigning containment scores to them.

Ticks' tricks: immunomodulatory effects of ixodid tick saliva at the cutaneous tick-host interface.

Due to changes in global climate, the geographic distribution of ticks and tick-borne infections is increasing and represents a growing global health concern for humans. Ticks of the genus Ixodidae are globally abundant and transmit a wide variety of pathogens that cause human infections, including tick-borne encephalitis and Lyme borreliosis. The transmission of pathogens into human skin while blood feeding causes changes in the local immune cell network and has various effects on structural skin cells, including sensory neurons.

The choice of study designs of diagnostic accuracy using Borrelia specific IgG and IgM antibodies for the diagnosis of Lyme borreliosis.

Background: Laboratory diagnosis of Lyme borreliosis (LB) is used in a variety of clinical settings where a range of other diagnoses may be considered. Therefore, it is essential that diagnostic accuracy studies and literature reviews consider information from different types of studies and choices of sample groups. The quality of patient selection is important to minimize the risk of misclassification.

Seasonally recurring patterns of dominant Crenothrix spp. in a European alluvial drinking water well: Significance and potential indicator role.

Iron and manganese (Fe/Mn) often lead to aesthetic quality issues in water supply. Strong and problematic black-brown particle formation was persistently observed in an alluvial drinking water well, even though oxygen enrichment probes, intended for in situ i.e.

24-Nor-ursodeoxycholic acid improves intestinal inflammation by targeting T17 pathogenicity and transdifferentiation.

Background: 24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC).

Objective: Since PSC strongly associates with T helper-type-like 17 (T17)-mediated intestinal inflammation, we explored NorUDCA's immunomodulatory potential on T17 cells.

Design: NorUDCA's impact on T17 differentiation was assessed using a CD4T adoptive transfer mouse model, and on intraepithelial T17 pathogenicity and transdifferentiation using an αCD3 stimulation model combined with interleukin-17A-fate-mapping.

Cyclophilin-CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8.

Monocytes and macrophages, as important constituents of the innate immune system, are equipped with multiple Toll-like-receptors (TLRs) to recognize invading pathogens, such as SARS-CoV-2, and mount an antiviral response. Nevertheless, their uncontrolled activation can lead to hyperinflammation seen in severe COVID-19. Surprisingly, we observed that recombinant SARS-CoV-2 Spike (S) and Nucleocapsid (N) proteins triggered only a weak proinflammatory response in human peripheral blood monocytes.

Using a harmonised study design and quantitative tool-box reveals major inconsistencies when investigating the main drivers of water and biofilm antibiotic resistomes in different rivers.

The spread of antibiotic resistance (ABR) via surface waters is of increasing concern. Large-scale studies investigating ABR drivers in different water bodies and habitats with uniform quantitative methods are largely missing. Here, we present a comprehensive investigation on ABR occurrence and drivers in water and biofilms of four Austrian rivers over a one-year-cycle using a harmonised quantitative tool-box and study-design.

Gauging antigen recognition by human primary T-cells featuring orthotopically exchanged TCRs of choice.

Understanding human T-cell antigen recognition in health and disease is becoming increasingly instrumental for monitoring T-cell responses to pathogen challenge and for the rational design of T-cell-based therapies targeting cancer, autoimmunity and organ transplant rejection. Here we showcase a quantitative imaging platform which is based on the use of planar glass-supported lipid bilayers (SLBs). The latter are functionalized with antigen (peptide-loaded HLA) as adhesion and costimulatory molecules (ICAM-1, B7-1) to serve as surrogate antigen presenting cell for antigen recognition by T-cells, which are equipped with T-cell antigen receptors (TCRs) sequenced from antigen-specific patient T-cells.

The bronchoalveolar lavage fluid as a marker for pulmonary fibrosis in diffuse parenchymal lung diseases.

Introduction: Diffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition.

In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus.

Background: Topical antiseptics are crucial for preventing infections and reducing transmission of pathogens. However, commonly used antiseptic agents have been reported to cause cross-resistance to other antimicrobials in bacteria, which has not yet been described in yeasts. This study aims to assess the in vitro efficacy of antiseptics against clinical and reference isolates of Candida albicans and Nakaseomyces glabratus, and whether prolonged exposure to antiseptics promotes the development of antifungal (cross)resistance.

Equivalent reduction of Escherichia coli by rinsing hands with cold and warm water.

Objective: Hand washing is considered an important public health intervention to reduce the burden of communicable diseases such as gastrointestinal and respiratory tract infections. Washbasins in public restrooms are often only equipped with cold water and it can be observed that people only rinse their hands briefly after using the toilet instead of washing them properly with soap. As there are no recommendations on the optimal water temperature for efficacy, we measured the efficacy of simple hand rinsing with cold (4°C) and warm (40°C) water for 10 and 20 seconds compared to the European Norm EN 1499 reference hand wash.

Zoonotic Tick-Borne Pathogens in Ixodes ricinus Complex (Acari: Ixodidae) From Urban and Peri-Urban Areas of Kosovo.

Introduction: Ixodes ricinus, the castor bean tick, is the most prevalent tick species in Europe. It favours habitats such as shrubs, deciduous and mixed forests, but can also be found in urban environments. Due to its high vector competence, it is of enormous veterinary as well as medical importance, transmitting tick-borne encephalitis (TBE) virus, Borrelia burgdorferi s.

Optimising Transformation Efficiency in Unravelling the Role of the Restriction-Modification System of and .

spp. are transmitted to humans by the bite of an infected tick. In Europe, and are the main causative agents of Lyme borreliosis, one of the most prevalent tick-borne diseases in the northern hemisphere.

Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function.

FOXP3 regulatory T cells (Treg cells) are key for immune homeostasis. Here, we reveal that nuclear receptor corepressor 1 (NCOR1) controls naïve and effector Treg cell states. Upon NCOR1 deletion in T cells, effector Treg cell frequencies were elevated in mice and in in vitro-generated human Treg cells.

SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis.

The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera.

TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation.

Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)-modified T cells and call for alternative antigen receptor designs for effective T cell-based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR-T cells, and did not depend-unlike sensitized peptide/MHC detection by conventional T cells-on CD4 or CD8 coreceptor engagement.

Advanced Quantification of Receptor-Ligand Interaction Lifetimes via Single-Molecule FRET Microscopy.

Receptor-ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR-pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists.