B Cells With Complementary B Cell Receptors Can Kill Each Other.

B cells differentiate from hematopoietic stem cells in the bone marrow (BM) and migrate as transitional cells to the spleen where final maturation takes place. Due to the enormous diversity in variable (V) regions of B cell receptors for antigen (BCR), B cells with complementary BCRs are likely to be generated. These could encounter each other in the BM or in secondary lymphoid organs.

The Atlantic Cod MHC I compartment has the properties needed for cross-presentation in the absence of MHC II.

Atlantic cod has a peculiar immune system, characterized by the loss of Major Histocompatibility Complex (MHC) class II pathway, and an extreme expansion of the MHC class I gene repertoire. This has led to the hypothesis that some of the MHC I variants have replaced MHC II by presenting exogenous-peptides in a process similar to cross-presentation. In mammals, MHC I loads endogenous antigens in the endoplasmic reticulum, but we recently found that different Atlantic cod MHC I gene variants traffic to endolysosomes.

Differential Talin cleavage in transformed and non-transformed cells and its consequences.

This study investigates differences in focal adhesion (FA) morphology and Talin cleavage levels between transformed and non-transformed cell lines. Utilizing fluorescently tagged wild-type Talin and Talin mutants with calpain cleavage site mutations, FA structures were visualized. Mutations in different Talin cleavage sites showed varying impacts on FA morphology and distribution across melanoma cell lines (Meljuso, A375P, A2058) and a non-transformed cell line (HFF).

Clean air in Europe for all! Taking stock of the proposed revision to the ambient air quality directives: a joint ERS, HEI and ISEE workshop report.

Ambient air pollution is a major public health concern and comprehensive new legislation is currently being considered to improve air quality in Europe. The European Respiratory Society (ERS), Health Effects Institute (HEI), and International Society for Environmental Epidemiology (ISEE) organised a joint meeting on May 24, 2023 in Brussels, Belgium, to review and critically evaluate the latest evidence on the health effects of air pollution and discuss ongoing revisions of the European Ambient Air Quality Directives (AAQDs). A multi-disciplinary expert group of air pollution and health researchers, patient and medical societies, and policy representatives participated.

Rai14 is a novel interactor of Invariant chain that regulates macropinocytosis.

Invariant chain (Ii, CD74) is a type II transmembrane glycoprotein that acts as a chaperone and facilitates the folding and transport of MHC II chains. By assisting the assembly and subcellular targeting of MHC II complexes, Ii has a wide impact on the functions of antigen-presenting cells such as antigen processing, endocytic maturation, signal transduction, cell migration, and macropinocytosis. Ii is a multifunctional molecule that can alter endocytic traffic and has several interacting molecules.

Saddlepoint approximations to score test statistics in logistic regression for analyzing genome-wide association studies.

We investigate saddlepoint approximations of tail probabilities of the score test statistic in logistic regression for genome-wide association studies. The inaccuracy in the normal approximation of the score test statistic increases with increasing imbalance in the response and with decreasing minor allele counts. Applying saddlepoint approximation methods greatly improve the accuracy, even far out in the tails of the distribution.

Atlantic cod () MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals.

Major histocompatibility complex (MHC) class I and II are crucial for the adaptive immune system because they are involved in peptide presentation to T cells. Until recently, it was believed that MHC genes and their associated immune components had been conserved since their evolutionary emergence in jawed fish. However, sequencing of the Atlantic cod () genome revealed a loss of MHC class II genes, and an extreme expansion of MHC class I genes.

Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton.

Lysosomal signaling facilitates the migration of immune cells by releasing Ca2+ to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the trans-Golgi network (TGN).

De novo formation of early endosomes during Rab5-to-Rab7a transition.

Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosome. Here, we provide new insight into the mechanism of endosomal maturation, for which we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a.

Invariant chain regulates endosomal fusion and maturation through an interaction with the SNARE Vti1b.

The invariant chain (Ii, also known as CD74) is a multifunctional regulator of adaptive immune responses and is responsible for sorting major histocompatibility complex class I and class II (MHCI and MHCII, respectively) molecules, as well as other Ii-associated molecules, to a specific endosomal pathway. When Ii is expressed, endosomal maturation and proteolytic degradation of proteins are delayed and, in non-antigen presenting cells, the endosomal size increases, but the molecular mechanisms underlying this are not known. We identified that a SNARE, Vti1b, is essential for regulating these Ii-induced effects.

Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum.

The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism.

Sleep patterns and insomnia in a large population-based study of middle-aged and older adults: The Tromsø study 2015-2016.

Epidemiological studies assessing adult sleep duration have yielded inconsistent findings and there are still large variations in estimation of insomnia prevalence according to the most recent diagnostic criteria. Our objective was to describe sleep patterns in a large population of middle-aged and older adults, by employing accurate measures of both sleep duration and insomnia. Data stem from the Tromsø Study (2015-2016), an ongoing population-based study in northern Norway comprising citizens aged 40 years and older (n = 21,083, attendance = 64.

Micro-stepping extended focus reduces photobleaching and preserves structured illumination super-resolution features.

Despite progress made in confocal microscopy, even fast systems still have insufficient temporal resolution for detailed live-cell volume imaging, such as tracking rapid movement of membrane vesicles in three-dimensional space. Depending on the shortfall, this may result in undersampling and/or motion artifacts that ultimately limit the quality of the imaging data. By sacrificing detailed information in the -direction, we propose a new imaging modality that involves capturing fast 'projections' from the field of depth and shortens imaging time by approximately an order of magnitude as compared to standard volumetric confocal imaging.

Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells.

Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren's syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level.

Receptor-Mediated Endocytosis of VEGF-A in Rat Liver Sinusoidal Endothelial Cells.

Background And Aims: Vascular endothelial growth factor (VEGF) receptors (VEGFR1 and VEGFR2) bind VEGF-A with high affinity. This study sought to determine the relative contributions of these two receptors to receptor-mediated endocytosis of VEGF-A and to clarify their endocytic itineraries in rat liver sinusoidal endothelial cells (LSECs).

Methods: Isolated LSECs and radiolabeled VEGF-A were used to examine surface binding and receptor-mediated endocytosis.

Disentangling the immune response and host-pathogen interactions in Francisella noatunensis infected Atlantic cod.

The genetic repertoire underlying teleost immunity has been shown to be highly variable. A rare example is Atlantic cod and its relatives Gadiformes that lacks a hallmark of vertebrate immunity: Major Histocompatibility Complex class II. No immunological studies so far have fully unraveled the functionality of this particular immune system.

Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity.

Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood.

Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity.

Eradication of tumors by the immune system relies on the efficient activation of a T-cell response. For many years, the main focus of cancer immunotherapy has been on cytotoxic CD8 T-cell. However, stimulation of CD4 helper T cells is critical for the promotion and maintenance of immune memory, thus a good vaccine should evoke a two-dimensional T-cell response.

Antifungal activity of well-defined chito-oligosaccharide preparations against medically relevant yeasts.

Due to their antifungal activity, chitosan and its derivatives have potential to be used for treating yeast infections in humans. However, to be considered for use in human medicine, it is necessary to control and know the chemical composition of the compound, which is not always the case for polymeric chitosans. Here, we analyze the antifungal activity of a soluble and well-defined chito-oligosaccharide (CHOS) with an average polymerization degree (DPn) of 32 and fraction of acetylation (FA) of 0.

Scrotum bipartite in sheep as a parameter indicative of adaptation to semi-arid climates: A thermographic and reproductive study.

With the objective of assessing the influence of scrotum bipartition on scrotum-testiclar thermoregulation and semen quality in sheep native to a semiarid region, 14 adult crossbred rams were placed into groups, GI (7 with bipartition in the scrotum) and GII (7 without bipartition). Images were taken of the caudal scrotum surface using a Fluke (Ti25) thermographic camera, for temperature analysis. Two semen collections were made, at an eight-day interval, by electroejaculation, to analyze macroscopic and microscopic parameters.

TBC1D5 controls the GTPase cycle of Rab7b.

Rab GTPases are key regulators of intracellular trafficking, and cycle between a GTP-bound active state and a GDP-bound inactive state. This cycle is regulated by guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several efforts have been made in connecting the correct GEFs and GAPs to their specific Rab.