This resistance mechanism was confirmed in primary CLL cells from patients. In addition, pharmacological inhibition of actin dynamics in combination with blocking antibodies increased conjugation frequency and improved CLL cell elimination by NK cells. Together our results highlight the critical role of CLL cell actin cytoskeleton in driving resistance against NK cell cytotoxicity and provide new potential therapeutic point of intervention to target CLL immune escape.The function of mucosal-associated invariant T (MAIT) cells highly depends on the mode of activation, either by recognition of bacterial metabolites via their T cell receptor (TCR) or in a TCR-independent manner via cytokines. PI3K inhibitor The underlying molecular mechanisms are not entirely understood. To define the activation of MAIT cells on the molecular level, we applied a multi-omics approach with untargeted transcriptomics, proteomics and metabolomics. Transcriptomic analysis of E. coli- and TCR-activated MAIT cells showed a distinct transcriptional reprogramming, including altered pathways, transcription factors and effector molecules. We validated the consequences of this reprogramming on the phenotype by proteomics and metabolomics. Thus, and to distinguish between TCR-dependent and -independent activation, MAIT cells were stimulated with IL12/IL18, anti-CD3/CD28 or both. Only a combination of both led to full activation of MAIT cells, comparable to activation by E. coli. Using an integrated network-based approach, we identified key drivers of the distinct modes of activation, including cytokines and transcription factors, as well as negative feedback regulators like TWIST1 or LAG3. Taken together, we present novel insights into the biological function of MAIT cells, which may represent a basis for therapeutic approaches to target MAIT cells in pathological conditions.Fcγ receptors (FcγR), cell-surface glycoproteins that bind antigen-IgG complexes, control both humoral and cellular immune responses. The FCGR locus on chromosome 1q23.3 comprises five homologous genes encoding low-affinity FcγRII and FcγRIII, and displays functionally relevant polymorphism that impacts on human health. Recurrent events of non-allelic homologous recombination across the FCGR locus result in copy-number variation of ~82.5 kbp-long fragments known as copy-number regions (CNR). Here, we characterize a recently described deletion that we name CNR5, which results in loss of FCGR3A, FCGR3B, and FCGR2C, and generation of a recombinant FCGR3B/A gene. We show that the CNR5 recombination spot lies at the beginning of the third FCGR3 intron. Although the FCGR3B/A-encoded hybrid protein CD16B/A reaches the plasma membrane in transfected cells, its possible natural expression, predictably restricted to neutrophils, could not be demonstrated in resting or interferon γ-stimulated cells. As the CNR5-deletionl genetic variations in the locus and warrants additional studies on their putative clinical impact. In conclusion, our study confirms important ethnic variation at the FCGR locus; it shows a distinctive FCGR polymorphism distribution in Ecuador highlands; provides a molecular characterization of a novel CNR5-deletion associated with CD16A and CD16B deficiency; and confirms its presence in that population.The pink-red color of traditional sausages (cured meat) is the result of nitrite addition and the formation of nitrosomyoglobin. However, the pleasant color of processed meat products is a side effect of nitrite addition while the main anticipated goal is to suppress the germination of clostridial spores. The fungus Monascus is known as a producer of oligoketide pigments, which are used in Asian countries, especially in China, for coloring foods, including meat products. Although, different biological activities of Monascus pigments have been tested and confirmed in many studies, their effect on germination of bacterial spores has never been investigated. This study is focused on testing the activity of red yeast rice (RYR) extract, containing monascin, rubropunctatin, rubropunctamine complexes and monascuspiloin as the main pigments, on germination of Clostridium and Bacillus spores. It was found that addition of nitrite alone, at the permitted concentration, had no effect on spore germination. However, the combined effects of nitrite with NaCl, tested after addition of pickling salt, was efficient in inhibiting the germination of C. beijerinckii spores but had no effect on B. subtilis spores. In contrast, total suppression of C. beijerinckii spore germination was reached after addition of RYR extract to the medium at a concentration of 2% v/v. For B. subtilis, total inhibition of spore germination was observed only after addition of 4% v/v RYR extract to the medium containing 1.3% w/w NaCl.We review the role of signaling pathways in regulation of the key processes of merozoite egress and red blood cell invasion by Plasmodium falciparum and, in particular, the importance of the second messengers, cAMP and Ca2+, and cyclic nucleotide dependent kinases. cAMP-dependent protein kinase (PKA) is comprised of cAMP-binding regulatory, and catalytic subunits. The less well conserved cAMP-binding pockets should make cAMP analogs attractive drug leads, but this approach is compromised by the poor membrane permeability of cyclic nucleotides. We discuss how the conserved nature of ATP-binding pockets makes ATP analogs inherently prone to off-target effects and how ATP analogs and genetic manipulation can be useful research tools to examine this. We suggest that targeting PKA interaction partners as well as substrates, or developing inhibitors based on PKA interaction sites or phosphorylation sites in PKA substrates, may provide viable alternative approaches for the development of anti-malarial drugs. Proximies.Soil microorganisms play important roles in crop production and sustainable agricultural management. However, soil conditions and crop selection are key determining factors for soil microbial communities. This study investigated the effect of plant types and soil salinity on the microbial community of interspecific interaction zone (II) based on the sorghum/peanut intercropping system. Microbial community diversity and composition were determined through PacBio single molecule, real-time sequencing of 16S rDNA and internal transcribed spacer (ITS) genes. Results showed Proteobacteria, Bacteroidota, and Acidobacteriota to be the dominant bacterial phyla in IP, II, and IS, whereas Ascomycota, Basidiomycota, and Mucoromycota were the dominant fungal phyla. Under salt-treated soil conditions, the plants-specific response altered the composition of the microbial community (diversity and abundance). Additionally, the interspecific interactions were also helpful for maintaining the stability and ecological functions of microbial communities by restructuring the otherwise stable core microbiome.