IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.

Background: Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).

Methods: To determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.

CO-induced drastic decharging of dielectric surfaces in aqueous suspensions.

We study the influence of airborne CO on the charge state of carboxylate stabilized polymer latex particles suspended in aqueous electrolytes. We combine conductometric experiments interpreted in terms of Hessinger's conductivity model with Poisson-Boltzmann cell (PBC) model calculations with charge regulation boundary conditions. Without CO, a minority of the weakly acidic surface groups are dissociated and only a fraction of the total number of counter-ions actually contribute to conductivity.

The Ashkenazi-Centric G334R Variant of is Severely Impaired for Transactivation but Retains Tumor Suppressor Function in a Mouse Model.

Mutations in the tumor suppressor gene are the most abundant genetic occurrences in cancer. Some of these mutations lead to loss of function of p53 protein, some are gain of function, and some variants are hypomorphic (partially functional). Currently, there is no clinical distinction between different p53 mutations and cancer therapy or prognosis.

Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy.

Epigenetic reinforcement of T cell exhaustion is known to be a major barrier limiting T cell responses during immunotherapy. However, the core epigenetic regulators restricting antitumor immunity during prolonged antigen exposure are not clear. We investigated three commonly mutated epigenetic regulators that promote clonal hematopoiesis to determine whether they affect T cell stemness and response to checkpoint blockade immunotherapy.

Computationally accelerated identification of P-glycoprotein inhibitors.

Overexpression of the polyspecific efflux transporter, P-glycoprotein (P-gp, MDR1, ), is a major mechanism by which cancer cells acquire multidrug resistance (MDR), the resistance to diverse chemotherapeutic drugs. Inhibiting drug transport by P-gp can resensitize cancer cells to chemotherapy, but there are no P-gp inhibitors available to patients. Clinically unsuccessful P-gp inhibitors tend to bind at the pump's transmembrane drug binding domains and are often P-gp transport substrates, resulting in lowered intracellular concentration of the drug and altered pharmacokinetics.

Something has sort of opened up for me: psychology students' reflections after participating in an apprenticeship training model.

Typically, psychotherapy training comprises of didactic approaches and clinical practice under supervision, with students rarely having the opportunity to observe other therapists' work in real time. Many trades and professions employ apprenticeship to teach new skills. However, it is rarely employed in psychotherapist training.

Synergy of the mirror neuron system and the mentalizing system in a single brain and between brains during joint actions.

Cooperative action involves the simulation of actions and their co-representation by two or more people. This requires the involvement of two complex brain systems: the mirror neuron system (MNS) and the mentalizing system (MENT), both of critical importance for successful social interaction. However, their internal organization and the potential synergy of both systems during joint actions (JA) are yet to be determined.

An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification.

RNA base editing relies on the introduction of adenosine-to-inosine changes into target RNAs in a highly programmable manner in order to repair disease-causing mutations. Here, we propose that RNA base editing could be broadly applied to perturb protein function by removal of regulatory phosphorylation and acetylation sites. We demonstrate the feasibility on more than 70 sites in various signaling proteins and identify key determinants for high editing efficiency and potent down-stream effects.

bites promote allergic skin inflammation and intestinal tuft and mast cell expansion in mice.

Background: Tick bites often promote local allergic reactions in the skin and predispose to red meat allergy. The mechanisms involved in these processes are not fully understood. Here we investigated the local changes to the skin and intestine induced by tick bites.

Multiple transatlantic incursions of highly pathogenic avian influenza clade 2.3.4.4b A(H5N5) virus into North America and spillover to mammals.

Highly pathogenic avian influenza (HPAI) viruses have spread at an unprecedented scale, leading to mass mortalities in birds and mammals. In 2023, a transatlantic incursion of HPAI A(H5N5) viruses into North America was detected, followed shortly thereafter by a mammalian detection. As these A(H5N5) viruses were similar to contemporary viruses described in Eurasia, the transatlantic spread of A(H5N5) viruses was most likely facilitated by pelagic seabirds.

NLRC5 senses NAD depletion, forming a PANoptosome and driving PANoptosis and inflammation.

NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5's role in response to infections, PAMPs, DAMPs, and cytokines.

Mice Lacking Mrs2 Magnesium Transporter are Hypophagic and Thin When Maintained on a High-Fat Diet.

Genes regulating body fat are shared with high fidelity by mice and humans, indicating that mouse knockout (KO) phenotyping might identify valuable antiobesity drug targets. Male Mrs2 magnesium transporter (Mrs2) KO mice were recently reported as thin when fed a high-fat diet (HFD). They also exhibited increased energy expenditure (EE)/body weight and had beiged adipocytes that, along with isolated hepatocytes, demonstrated increased oxygen consumption, suggesting that increased EE drove the thin phenotype.

Characterization of the clinically approved MRI tracer resotran for magnetic particle imaging in a comparison study.

The availability of magnetic nanoparticles (MNPs) with medical approval for human intervention is fundamental to the clinical translation of magnetic particle imaging (MPI). In this work, we thoroughly evaluate and compare the magnetic properties of an magnetic resonance imaging (MRI) approved tracer to validate its performance for MPI in future human trials.We analyze whether the recently approved MRI tracer Resotran is suitable for MPI.

Cross-species spill-over potential of the H9N2 bat influenza A virus.

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2).

Genetic ablation of induces a lethal disruption of the MICOS complex.

The mitochondrial contact site and cristae organizing system (MICOS) is important for crista junction formation and for maintaining inner mitochondrial membrane architecture. A key component of the MICOS complex is MIC60, which has been well studied in yeast and cell culture models. However, only one recent study has demonstrated the embryonic lethality of losing (the gene encoding MIC60) expression.

Optogenetic action potentials and intrinsic pacemaker interplay in retrogradely identified midbrain dopamine neurons.

Dissecting the diversity of midbrain dopamine (DA) neurons by optotagging is a promising addition to better identify their functional properties and contribution to motivated behavior. Retrograde molecular targeting of DA neurons with specific axonal projection allows further refinement of this approach. Here, we focus on adult mouse DA neurons in the substantia nigra pars compacta (SNc) projecting to dorsal striatum (DS) by demonstrating the selectivity of a floxed AAV9-based retrograde channelrhodopsin-eYFP (ChR-eYFP) labeling approach in DAT-cre mice.

Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling.

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor.

Electrokinetic effects of ambient and excess carbonization of dielectric surfaces in aqueous environments.

The charge state of surfaces in contact with aqueous electrolytes is crucial for the performance and stability of dielectric surfaces in general and lyophobic colloids in particular. Thus far the role of adsorbed molecular CO remained largely unexplored. The aim of the present investigation is to study the de-charging and re-charging for two model surfaces upon addition of CO and/or 1:1 electrolytes (NaCl, HCl) under precisely controlled boundary conditions up to millimolar concentrations of additives.

CAR T-cell Design-dependent Remodeling of the Brain Tumor Immune Microenvironment Modulates Tumor-associated Macrophages and Anti-glioma Activity.

Unlabelled: Understanding the intricate dynamics between adoptively transferred immune cells and the brain tumor immune microenvironment (TIME) is crucial for the development of effective T cell-based immunotherapies. In this study, we investigated the influence of the TIME and chimeric antigen receptor (CAR) design on the anti-glioma activity of B7-H3-specific CAR T-cells. Using an immunocompetent glioma model, we evaluated a panel of seven fully murine B7-H3 CARs with variations in transmembrane, costimulatory, and activation domains.

A Meta-Analysis of the Efficacy of Pomalidomide-Based Regimens for the Treatment of Relapsed/Refractory Multiple Myeloma After Lenalidomide Exposure.

Introduction: The objective was to assess the benefit of pomalidomide-based combination regimens in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide. A pooled estimate was obtained for efficacy outcomes including overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS) based on multiple trials conducted in this patient population.

Patients And Methods: A literature search was conducted on March 22, 2022 for relevant trials published between January 1, 2016 and the search date.

CXCR6 orchestrates brain CD8 T cell residency and limits mouse Alzheimer's disease pathology.

Neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8 T cells that coexpress CXCR6 and PD-1 and are in proximity to plaque-associated microglia in human and mouse AD brains. We also establish that CD8 T cells restrict AD pathologies, including β-amyloid deposition and cognitive decline.

(plastid starch phosphorylase) is duplicated and essential for normal starch granule phenotype in tubers of L.

Reserve starch from seeds and tubers is a crucial plant product for human survival. Much research has been devoted to quantitative and qualitative aspects of starch synthesis and its relation to abiotic factors of importance in agriculture. Certain aspects of genetic factors and enzymes influencing carbon assimilation into starch granules remain elusive after many decades of research.