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Cholera Toxin Subunit B as Adjuvant--An Accelerator in Protective Immunity and a Break in Autoimmunity.

Cholera toxin subunit B (CTB) is the nontoxic portion of cholera toxin. Its affinity to the monosialotetrahexosylganglioside (GM1) that is broadly distributed in a variety of cell types including epithelial cells of the gut and antigen presenting cells, macrophages, dendritic cells, and B cells, allows its optimal access to the immune system. CTB can easily be expressed on its own in a variety of organisms, and several approaches can be used to couple it to antigens, either by genetic fusion or by chemical manipulation, leading to strongly enhanced immune responses to the antigens. In autoimmu

Effect of starvation on the endocytic pathway in Dictyostelium cells.

Dictyostelium discoideum amoebae have been used extensively to study the structure and dynamics of the endocytic pathway. Here, we show that while the general structure of the endocytic pathway is maintained in starved cells, its dynamics rapidly slow down. In addition, analysis of apm3 and lvsB mutants reveals that the functional organization of the endocytic pathway is profoundly modified upon starvation. Indeed, in these mutant cells, some of the defects observed in rich medium persist in starved cells, notably an abnormally slow transfer of endocytosed material between endocytic compartmen

Formation of the vulva in Caenorhabditis elegans: a paradigm for organogenesis.

The genes involved in the inductive interactions that specify cell fates in the vulva of Caenorhabditis elegans are known in some detail. However, little is known about the morphogenesis of this organ. Using a combination of cell biological and anatomical approaches, we have determined a complete morphogenetic pathway of cellular events that lead to the formation of the vulva. These events include reproducible cell divisions, migrations, remodeling of adherens junctions, cell fusions and muscle attachments. In the course of these events, an epithelial channel comprising a stack of 7 toroidal c…

Pathogenesis of Shigella diarrhea: XVII. A mammalian cell membrane glycolipid, Gb3, is required but not sufficient to confer sensitivity to Shiga toxin.

Shiga toxin recognizes a galactose-alpha 1-->4-galactose terminal glycolipid, globotriaosylceramide (Gb3), in sensitive mammalian cells and is translocated by endocytosis to the cytoplasm, where it blocks protein synthesis. To determine if Gb3 is both required and sufficient for toxicity, Gb3 content in cells was altered by blocking key biosynthetic or degradative path enzymes with specific inhibitors. The resulting decrease or increase in cellular Gb3 was associated with a decrease or increase in binding of and response to Shiga toxin. Toxin-resistant Gb3-deficient variants of sensitive cells

No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D.

A 31-year-old female patient with xeroderma pigmentosum (XP) XP43KO was assigned to complementation group D by the cell-fusion complementation methods. Cultured XP43KO cells from our patient had the defective DNA repair phenotype showing a residual level of ultraviolet (UV)-induced unscheduled DNA synthesis (45% of normal) and an eightfold higher sensitivity to 254-nm UV killing, compared with normal cells. The phototest on the patient revealed the delayed maximum reaction to UV-B-induced erythema and lower minimal erythema doses at 290- and 300-nm monochromatic wavelengths. However, the XP43K

Effects of hypotonic swelling on the cellular distribution and expression of pI(Cln) in human nonpigmented ciliary epithelial cells.

PURPOSE: It has been proposed that pI(Cln), a highly acidic protein, is a candidate gene product related to the swelling-activated chloride (Cl-) channel Icl.swell in mammalian cells. However, no consensus has been reached as to whether this relationship is direct or indirect. Recently the cDNA for pI(Cln) was isolated from human ciliary epithelial cells. To learn more about the structure-function of pI(Cln) we attempted to: i) overexpress pI(Cln) as a fusion protein in bacteria; ii) carry out its purification; iii) generate polyclonal antibodies to study its expression and cellular localizati

HIV-1 cell-to-cell infection of macrophages escapes restriction by the BST-2 host cell factor independently of the Vpu counteracting viral protein.

As HIV-1 target cells, macrophages can be infected by cell-to-cell virus transfer from infected T cells through cell-cell fusion leading to the formation of virus-productive multinucleated giant cells (MGCs). We recently demonstrated that this route of infection escaped host cell restriction acting on the early steps of the viral life cycle. Here, we investigated whether restriction factors acting on late steps of HIV-1 replication were also bypassed in virus cell-to-cell infection of macrophages. We focused on the impact of the interferon(IFN)-induced factor BST-2/tetherin acting on virus rel…

A fusing mumps virus variant selected from a nonfusing parent with the neuraminidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid.

A fusing variant of the nonfusing O'Take strain of mumps virus was obtained by growing virus under the selective pressure of the competitive … cate that the neuraminidase enzyme of the mumps virus HN glycoprotein is involved in modulating the cell fusion cytopathology of mumps virus infections.

Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), th

Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness.

This paper investigates the effect of altering the protein expression dynamics of the bHLH transcription factor Her6 at the single-cell level in the embryonic zebrafish telencephalon. Using a homozygote endogenous Her6:Venus reporter and 4D single-cell tracking, we show that Her6 oscillates in neural telencephalic progenitors and that the fusion of protein destabilisation (PEST) domain alters its expression dynamics, causing most cells to downregulate Her6 prematurely. However, counterintuitively, oscillatory cells increase, with some expressing Her6 at high levels, resulting in increased hete

Mitochondria Quality Control and Male Fertility.

Mitochondria are pivotal to cellular homeostasis, performing vital functions such as bioenergetics, biosynthesis, and cell signalling. Proper maintenance of these processes is crucial to prevent disease development and ensure optimal cell function. Mitochondrial dynamics, including fission, fusion, biogenesis, mitophagy, and apoptosis, maintain mitochondrial quality control, which is essential for overall cell health. In male reproduction, mitochondria play a pivotal role in germ cell development and any defects in mitochondrial quality can have serious consequences on male fertility. Reactive

Anticancer potential of mebendazole against chronic myeloid leukemia: in silico and in vitro studies revealed new insights about the mechanism of action.

Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, particularly the T315I gate-keeper mutation, cause resistance in patients. As a result, broad-spectrum ABL1 medicines are desperately needed. In order to screen potential drugs targeting CML, mebendazole (MBZ) was subjected to the in vitro test against CML cell lines (K562 and FEPS) and computational assays. The antiproliferative effect of MBZ an

On the effectiveness of proton boron fusion therapy (PBFT) at cellular level.

The present work introduced a framework to investigate the effectiveness of proton boron fusion therapy (PBFT) at the cellular level. The framework consisted of a cell array generator program coupled with PHITS Monte Carlo package with a dedicated terminal-based code editor that was developed in this work. The framework enabled users to model large cell arrays with normal, all boron, and random boron filled cytoplasm, to investigate the underlying mechanism of PBFT. It was found that alpha particles and neutrons could be produced in absence of boron mainly because of nuclear reaction induced b

Lipidomics Reveals Triacylglycerol Accumulation Due to Impaired Fatty Acid Flux in Opa1-Disrupted Fibroblasts.

OPA1 is a dynamin GTPase implicated in mitochondrial membrane fusion. Despite its involvement in lipid remodeling, the function of OPA1 has never been analyzed by whole-cell lipidomics. We used a nontargeted, reversed-phase lipidomics approach, validated for cell cultures, to investigate OPA1-inactivated mouse embryonic fibroblasts ( Opa1 -/- MEFs). This led to the identification of a wide range of 14 different lipid subclasses comprising 212 accurately detected lipids. Multivariate and univariate statistical analyses were then carried out to assess the differences between the Opa1 -/- and Opa

Сравнительный обзор вирусного проникновения и связи при крупных и гигантских вирусных инфекциях dsDNA.

Вирусы поступают в клетки хост-компьютеров с помощью нескольких механизмов, включая эндоцитоз, макропиноцитоз и фагоцитоз. Они также могут зажигать на плазменной мембране и распространяться внутри хост-комплексного синтеза или синцития. Механизм, используемый определенным вирусным штаммом, зависит от его внешней топологии и протеомы, а также типа входимой клетки. В настоящем сравнительном обзоре рассматриваются рецепторы клеточной привязанности и пути проникновения вирусов dsDNA, принадлежащих семьям Adenoviridae, Baculoviridae, Herpesviridae и Nucleocytoplasmic Крупные вирусы ДНК (NCLDV), при

Совпадение в аннотации оригинала
Viruses enter host cells via several mechanisms, including endocytosis, macropinocytosis, and phagocytosis. They can also fuse at the plasma membrane and can spread within the host via cell-to-cell fusion or syncytia. The mechanism used by a given viral strain depends on its external topology and proteome and the type of cell being entered. This comparative …

Genetic interactions between the hedgehog co-receptors Gas1 and Boc regulate cell proliferation during murine palatogenesis.

Abnormal regulation of Sonic hedgehog (Shh) signaling has been described in a variety of human cancers and developmental anomalies, which highlights the essential role of this signaling molecule in cell cycle regulation and embryonic development. Gas1 and Boc are membrane co-receptors for Shh, which demonstrate overlapping domains of expression in the early face. This study aims to investigate potential interactions between these co-receptors during formation of the secondary palate. Mice with targeted mutation in Gas1 and Boc were used to generate Gas1; Boc compound mutants. The expression of

Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4.

Coxsackievirus B4 (CV-B4) belongs to the genus Enterovirus within the family Picornaviridae. To investigate target proteins recognized by T-cells in human enterovirus B infections, virus-encoded structural [VP0 (VP4 and VP2), VP1, VP3] and non-structural (2A, 2B, 2C, 3C and 3D) proteins were expressed and purified in Escherichia coli. Peripheral blood of 19 healthy adult donors was used to create enterovirus-specific T-cell lines by repeated stimulation with CV-B4 cell lysate antigen. T-cell lines responded in individual patterns, and responses to all purified proteins were observed. The most

The design and optimization of RNA trans-splicing molecules for skin cancer therapy.

Targeting tumor marker genes by RNA trans-splicing is a promising means to induce tumor cell-specific death. Using a screening system we designed RNA trans-splicing molecules (RTM) specifically binding the pre-mRNA of SLCO1B3, a marker gene in epidermolysis bullosa associated squamous cell carcinoma (EB-SCC). Specific trans-splicing, results in the fusion of the endogenous target mRNA of SLCO1B3 and the coding sequence of the suicide gene, provided by the RTM. SLCO1B3-specific RTMs containing HSV-tk were analyzed regarding their trans-splicing potential in a heterologous context using a SLCO1B

The interaction between Cdc42 and WASP is required for SDF-1-induced T-lymphocyte chemotaxis.

In studies aimed at further characterizing the cellular immunodeficiency of the Wiskott-Aldrich syndrome (WAS), we found that T lymphocytes from WAS patients display abnormal chemotaxis in response to the T-cell chemoattractant stromal cell-derived factor (SDF)-1. The Wiskott- Aldrich syndrome protein (WASP), together with the Rho family GTPase Cdc42, control stimulus-induced actin cytoskeleton rearrangements that are involved in cell motility. Because WASP is an effector of Cdc42, we further studied how Cdc42 and WASP are involved in SDF-1-induced chemotaxis of T lymphocytes. We provide here

Functional CD40 ligand expressed by human blood dendritic cells is up-regulated by CD40 ligation.

We examined whether human blood dendritic cells (DCs) express a functional ligand for CD40 (CD40L). Human blood DCs expressed significant amounts of cell surface CD40L identical to that expressed on activated T cells, as detected by mAb to CD40L or a chimeric CD40.Ig fusion protein (CD40.Ig). Stimulation through CD40 up-regulated protein and mRNA CD40L expression in DCs, B cells, and B cell lines. CD40-mediated CD40L expression was inhibited by a protein tyrosine kinase inhibitor, herbimycin, in a dose-dependent manner, suggesting that the induction of CD40L expression via CD40 requires protei