Revealing novel protein interaction partners of glyphosate in Escherichia coli.

Despite all debates about its safe use, glyphosate remains the most widely applied active ingredient in herbicide products, with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea.

Heat Treatment of Hazelnut Allergens Monitored by Polyclonal Sera and Epitope Fingerprinting.

Hazelnuts are frequently involved in IgE-mediated reactions and are the main cause of nut allergies in Europe. Most food products are processed before human consumption. Food processing can modify the structure, properties, and function of proteins, and as a result, the IgE-binding capacity of allergens can be affected.

Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways.

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case.

Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function.

Background: The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors indicating the need for adequately tuning CAR T cell functionality.

Methods: We leveraged a translational pipeline including biophysical characterization and structural prediction of the CAR binding moiety, evaluation of cellular avidity, synapse formation, T cell motility, and functional capacities under repetitive target challenge and in sustained tumor control.

Results: As an example of clinical relevance, we derived a panel of anti-Her2 CARs covering a 4-log affinity range, all expected to target the same Her2 epitope.

Meta-analysis of proteomics data from osteoblasts, bone, and blood: Insights into druggable targets, active factors, and potential biomarkers for bone biomaterial design.

Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%-10% of fractures.

"Tumor immunology meets oncology" (TIMO), 18 April-20 April 2024, in Brandenburg an der Havel, Germany.

The TIMO meeting XVIII 2024 covered both basic and translational tumor immunological topics, which were presented by national and international scientists and clinicians.

Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma.

Establishing a strategy for sequencing of T cell-redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunologic impact of bispecific T cell-engaging antibodies (BsAb) as bridging therapy (BT) to subsequent B-cell maturation antigen-directed chimeric antigen receptor T (CAR-T) cell therapies in 52 patients with RRMM. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared with chemotherapy, anti-CD38, or anti-SLAMF7 antibody-based regimens (46%).

Enhancing Colorimetric Detection of Nucleic Acids on Nitrocellulose Membranes: Cutting-Edge Applications in Diagnostics and Forensics.

This study re-introduces a protein-free rapid test method for nucleic acids on paper based lateral flow assays utilizing special multichannel nitrocellulose membranes and DNA-Gold conjugates, achieving significantly enhanced sensitivity, easier protocols, reduced time of detection, reduced costs of production and advanced multiplexing possibilities. A protein-free nucleic acid-based lateral flow assay (NALFA) with a limit of detection of 1 pmol of DNA is shown for the first time. The total production duration of such an assay was successfully reduced from the currently known several days to just a few hours.

Linker-specific monoclonal antibodies present a simple and reliable detection method for scFv-based CAR NK cells.

Chimeric antigen receptor (CAR) T cell therapies have demonstrated significant successes in treating cancer. Currently, there are six approved CAR T cell products available on the market that target different malignancies of the B cell lineage. However, to overcome the limitations of CAR T cell therapies, other immune cells are being investigated for CAR-based cell therapies.

The N terminus-only (trans) function of the adhesion G protein-coupled receptor latrophilin-1 controls multiple processes in reproduction of Caenorhabditis elegans.

Adhesion G protein-coupled receptors are unique molecules. They are able to transmit classical signals via G protein activation as well as mediate functions solely through their extracellular N termini, completely independently of the seven transmembrane helices domain and the C terminus. This dual mode of action is highly unusual for G protein-coupled receptors and allows for a plethora of possible cellular consequences.

Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy.

The importance of the immune system in regulating tumor growth by inducing immune cell-mediated cytotoxicity associated with patients' outcomes has been highlighted in the past years by an increasing life expectancy in patients with cancer on treatment with different immunotherapeutics. However, tumors often escape immune surveillance, which is accomplished by different mechanisms. Recent studies demonstrated an essential role of small non-coding RNAs, such as microRNAs (miRNAs), in the post-transcriptional control of immune modulatory molecules.

Adeno-Associated Virus Vectors-a Target of Cellular and Humoral Immunity-are Expanding Their Reach Toward Hematopoietic Stem Cell Modification and Immunotherapies.

All current market-approved gene therapy medical products for gene therapy of monogenic diseases rely on adeno-associated virus (AAV) vectors. Advances in gene editing technologies and vector engineering have expanded the spectrum of target cells and, thus, diseases that can be addressed. Consequently, AAV vectors are now being explored to modify cells of the hematopoietic system, including hematopoietic stem and progenitor cells (HSPCs), to develop novel strategies to treat monogenic diseases, but also to generate cell- and vaccine-based immunotherapies.

Cognitive performance in adults with post-COVID syndrome: Results from a German case-control study.

Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany.

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking.

Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model.

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection , we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant.

Laccase-Treated Polystyrene Surfaces with Caffeic Acid, Dopamine, and L-3,4-Dihydroxyphenylalanine Substrates Facilitate the Proliferation of Melanocytes and Embryonal Carcinoma Cells NTERA-2.

This study presents the effects of treating polystyrene (PS) cell culture plastic with oxidoreductase enzyme laccase and the catechol substrates caffeic acid (CA), L-DOPA, and dopamine on the culturing of normal human epidermal melanocytes (NHEMs) and human embryonal carcinoma cells (NTERA-2). The laccase-substrate treatment improved PS hydrophilicity and roughness, increasing NHEM and NTERA-2 adherence, proliferation, and NHEM melanogenesis to a level comparable with conventional plasma treatment. Cell adherence dynamics and proliferation were evaluated.

Synthesis and Characterization of DHODH Inhibitors Based on the Vidofludimus Scaffold with Pronounced Anti-SARS-CoV-2 Activity.

New strategies for the rapid development of broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Host-directed antivirals that target universal cellular metabolic pathways necessary for viral replication present a promising approach with broad-spectrum activity and low potential for development of viral resistance. Dihydroorotate dehydrogenase (DHODH) was identified as one of those universal host factors essential for the replication of many clinically relevant human pathogenic viruses.

A Spatial Transcriptomics Browser for Discovering Gene Expression Landscapes across Microscopic Tissue Sections.

A crucial feature of life is its spatial organization and compartmentalization on the molecular, cellular, and tissue levels. Spatial transcriptomics (ST) technology has opened a new chapter of the sequencing revolution, emerging rapidly with transformative effects across biology. This technique produces extensive and complex sequencing data, raising the need for computational methods for their comprehensive analysis and interpretation.

Deciphering the role of alternative splicing in neoplastic diseases for immune-oncological therapies.

Alternative splicing (AS) is an important molecular biological mechanism regulated by complex mechanisms involving a plethora of cis and trans-acting elements. Furthermore, AS is tissue specific and altered in various pathologies, including infectious, inflammatory, and neoplastic diseases. Recently developed immuno-oncological therapies include monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells targeting, among others, immune checkpoint (ICP) molecules.