[Hemophilia A in a male cat with intermittent lameness].

A 3-month-old domestic shorthair tomcat born on a farm was unsuccessfully treated with meloxicam for alternating lameness, fever and inappetence. On presentation, there was lameness (grade 2/4) of the right forelimb with mild swelling of the soft tissue. Rectal temperature was 39.

AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or AlphaFold-Multimer predictions.

AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays and AlphaFold-Multimer predictions.

CellFIE: CRISPR- and Cell Fusion-based Two-hybrid Interaction Mapping of Endogenous Proteins.

Numerous genetic methods facilitate the detection of binary protein-protein interactions (PPIs) by exogenous overexpression, which can lead to false results. Here, we describe CellFIE, a CRISPR- and cell fusion-based PPI detection method, which enables the mapping of interactions between endogenously tagged two-hybrid proteins. We demonstrate the specificity and reproducibility of CellFIE in a matrix mapping approach, validating the interactions of VCP with ASPL and UBXD1, and the self-interaction of TDP-43 under endogenous conditions.

High emissions of greenhouse gases from grasslands on peat and other organic soils.

Drainage has turned peatlands from a carbon sink into one of the world's largest greenhouse gas (GHG) sources from cultivated soils. We analyzed a unique data set (12 peatlands, 48 sites and 122 annual budgets) of mainly unpublished GHG emissions from grasslands on bog and fen peat as well as other soils rich in soil organic carbon (SOC) in Germany. Emissions and environmental variables were measured with identical methods.

Human NK cells require caspases for activation-induced proliferation and cytokine release but not for cytotoxicity.

Natural killer (NK) cells are innate immune cells involved in antiviral defence and tumour surveillance. To fulfil these tasks, NK cells make use of two major effector functions, cytokine and chemokine release and cytotoxicity. In addition, NK cells proliferate in response to cytokines such as IL-2.

Cannabis use at a young age is associated with psychotic experiences.

Background: Cannabis use is associated with psychosis and a range of subclinical psychiatric symptoms. The strength of this association depends on dosage and age at first use. The current study investigates whether level of cannabis exposure and starting age are associated with specific profiles of subclinical symptoms.

Toll-like receptor expression and function in subsets of human gammadelta T lymphocytes.

Two subsets of human gammadelta T cells can be identified by T cell receptor (TCR) V gene usage. Vdelta2Vgamma9 T cells dominate in peripheral blood and recognize microbe- or tumour-derived phosphoantigens. Vdelta1 T cells are abundant in mucosal tissue and recognize stress-induced MHC-related molecules.

Innate immune functions of human gammadelta T cells.

gammadelta T cells expressing the Vgamma9Vdelta2 T cell receptor (TCR) account for 1-10% of CD3(+) peripheral blood T lymphocytes. Vgamma9Vdelta2 T cells use their TCR as a pattern recognition receptor to sense the presence of infection through specific recognition of intermediates of the microbial non-mevalonate pathway of isoprenoid biosynthesis. Such phosphoantigens rapidly and selectively activate human gammadelta T cells to produce proinflammatory cytokines, notably interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha).

Correlation of hemocyte counts with different developmental parameters during the last larval instar of the tobacco hornworm, Manduca sexta.

We determined the changes in hemocyte titer and in the abundance of hemocyte types of the tobacco hornworm Manduca sexta during the fourth and fifth larval stadium and the beginning of the pupal stadium. As we analyzed the samples of individual insects at daily intervals, we were able to correlate phenotypical features, body weight, as well as total protein content and lysozyme activity in the hemolymph with the observations on hemocytes. In the course of the fifth larval stadium, the hemocyte titer decreased slightly and declined further after pupation.

Characterization of terminal deoxynucleotidyl transferase and polymerase mu in zebrafish.

Terminal deoxynucleotidyl transferase (TdT) contributes to the junctional diversity of immunoglobulin and T-cell receptors by incorporating nucleotides in a template-independent manner. A closely related enzyme, polymerase mu (polmu), a template-directed polymerase, plays a role in general end-joining double-strand break repair. We cloned zebrafish TdT and polmu and found them to be 43% identical in amino acid sequence.

Human gamma delta T cells: candidates for the development of immunotherapeutic strategies.

A numerically small subset of human T lymphocytes expresses a gamma delta T cell receptor (TCR). These gamma delta T cells share certain effector functions with alpha beta T cells as well as with NK cells and NKT cells. The major peripheral blood gamma delta T cell subset in healthy adults expresses a Vgamma9Vdelta2 TCR, which recognizes small phosphorylated metabolites referred to as phosphoantigens.

Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T lymphocytes.

TLR3 recognizes viral dsRNA and its synthetic mimetic polyinosinic-polycytidylic acid (poly(I:C)). TLR3 expression is commonly considered to be restricted to dendritic cells, NK cells, and fibroblasts. In this study we report that human gammadelta and alphabeta T lymphocytes also express TLR3, as shown by quantitative real-time PCR, flow cytometry, and confocal microscopy.

Differences between larval and pupal hemocytes of the tobacco hornworm, Manduca sexta, determined by monoclonal antibodies and density centrifugation.

Insect hemocytes play a major role in developmental processes where they disassociate and rebuild metamorphosing tissues while undergoing physiological changes themselves. We identified hemocyte changes from the last larval to the beginning of the pupal stage of the tobacco hornworm, Manduca sexta. Larval and pupal hemocytes behaved differently in a 40% Percoll density gradient.

Non-selective signal loss in the 13C CPMAS NMR spectra of soil organic matter. Investigations of particle size fractions.

In 13C cross-polarisation magic angle spinning (CPMAS) spectra of soil samples, the paramagnetic soil constituents partially discriminate against the signal intensity of the 13C atoms. The aim of the present study was to check to what extent this signal depression depends on the paramagnetic ion content and if it is selective for a certain kind of carbon species. The spectra of a variety of particle size fractions of five quite different soils were recorded.