Unmasking Verbal Defensiveness: The Role of Psychological Threat in Sentence Completion Tests.

Shedding light on the validity of sentence completion test (SCT) verbal defensiveness as an index of defensive behavior, the current two-part study examined the relationship between psychological threat and verbal defensiveness among military security and mission-critical team candidates using SCTs. Our study showed that as the threatening nature of SCT stems increased, defensive responses also increased, substantiating the link between psychological threat and defensive behavior. In addition, expert ratings of stem content revealed moderately strong relationships with defensive responses across two different SCTs, irrespective of their structural characteristics.

Motility-Induced Phase Separation Mediated by Bacterial Quorum Sensing.

We study motility-induced phase separation (MIPS) in living active matter, in which cells interact through chemical signaling, or quorum sensing. In contrast to previous theories of MIPS, our multiscale continuum model accounts explicitly for genetic regulation of signal production and motility. Through analysis and simulations, we derive a new criterion for the onset of MIPS that depends on features of the genetic network.

The gut ecosystem and immune tolerance.

The gastrointestinal tract is home to the largest microbial population in the human body. The gut microbiota plays significant roles in the development of the gut immune system and has a substantial impact on the maintenance of immune tolerance beginning in early life. These microbes interact with the immune system in a dynamic and interdependent manner.

Molecular mimicry and autoimmunity in the time of COVID-19.

Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs.

Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background.

We previously reported that nonobese diabetic (NOD) congenic mice (NOD.c3c4 mice) developed an autoimmune biliary disease (ABD) with similarities to human primary biliary cholangitis (PBC), including anti-mitochondrial antibodies and organ-specific biliary lymphocytic infiltrates. We narrowed the possible contributory regions in a novel NOD.

Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression.

The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation.

Dual B-cell targeting therapy ameliorates autoimmune cholangitis.

Objective: The ability to regulate B cell development has long been recognized to have therapeutic potential in a variety of autoimmune diseases. However, despite the presence of a classic autoantibody in primary biliary cholangitis (PBC), B cell depleting therapy and indeed therapy with other biologic agents has been disappointing. Unsuccessful treatment using Rituximab is associated with elevation of B-cell activating factor (BAFF) level.

The long and winding road: From mouse linkage studies to a novel human therapeutic pathway in type 1 diabetes.

Autoimmunity involves a loss of immune tolerance to self-proteins due to a combination of genetic susceptibility and environmental provocation, which generates autoreactive T and B cells. Genetic susceptibility affects lymphocyte autoreactivity at the level of central tolerance (e.g.

Endosomal Sequestration of TLR4 Antibody Induces Myeloid-Derived Suppressor Cells and Reverses Acute Type 1 Diabetes.

We previously showed that treating NOD mice with an agonistic monoclonal anti-TLR4/MD2 antibody (TLR4-Ab) reversed acute type 1 diabetes (T1D). Here, we show that TLR4-Ab reverses T1D by induction of myeloid-derived suppressor cells (MDSCs). Unbiased gene expression analysis after TLR4-Ab treatment demonstrated upregulation of genes associated with CD11b+Ly6G+ myeloid cells and downregulation of T-cell genes.

Quorum-sensing induced transitions between bistable steady-states for a cell-bulk ODE-PDE model with lux intracellular kinetics.

Intercellular signaling and communication are used by bacteria to regulate a variety of behaviors. In a type of cell-cell communication known as quorum sensing (QS), which is mediated by a diffusible signaling molecule called an autoinducer, bacteria can undergo sudden changes in their behavior at a colony-wide level when the density of cells exceeds a critical threshold. In mathematical models of QS behavior, these changes can include the switch-like emergence of intracellular oscillations through a Hopf bifurcation, or sudden transitions between bistable steady-states as a result of a saddle-node bifurcation of equilibria.

E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants.

Background And Aims: The increased frequency of urinary tract infections in patients with primary biliary cholangitis (PBC) and the cross-reactivity between the lipoyl domains (LD) of human pyruvate dehydrogenase complex (hPDC-E2) and Escherichia coli PDC-E2 (ePDC-E2) have long suggested a role of E. coli in causality of PBC. This issue, however, has remained speculative.

Enhancing Antigen Presentation and Inducing Antigen-Specific Immune Tolerance with Amphiphilic Peptides.

Ag-specific immunotherapy to restore immune tolerance to self-antigens, without global immune suppression, is a long-standing goal in the treatment of autoimmune disorders such as type 1 diabetes (T1D). However, vaccination with autoantigens such as insulin or glutamic acid decarboxylase have largely failed in human T1D trials. Induction and maintenance of peripheral tolerance by vaccination requires efficient autoantigen presentation by APCs.

The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function.

The myristoylated alanine-rich C-kinase substrate (MARCKS) and the MARCKS-related protein (MARCKSL1) are ubiquitous, highly conserved membrane-associated proteins involved in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis. MARCKS includes an N-terminal myristoylated domain for membrane binding, a highly conserved MARCKS Homology 2 (MH2) domain, and an effector domain (which is the phosphorylation site). MARCKS can sequester phosphatidylinositol-4, 5-diphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C (PKC), ultimately modulating the immune function.

Antibody glycosylation in autoimmune diseases.

The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover, antibody glycosylation may induce pathologic modifications and ultimately contribute to the development of autoimmune diseases. Thanks to progress in the analysis of glycosylation, more data are available on IgG and its subclass structures in the context of autoimmune diseases.

Enoxacin Up-Regulates MicroRNA Biogenesis and Down-Regulates Cytotoxic CD8 T-Cell Function in Autoimmune Cholangitis.

Background And Aims: Primary biliary cholangitis (PBC) is a prototypical organ-specific autoimmune disease that is mediated by autoreactive T-cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune-directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC).

Autoinflammatory and autoimmune conditions at the crossroad of COVID-19.

Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known.

Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis.

Glycosylation of antibodies, particularly in the Fc domain, critically modulate the ability of antibodies to bind to FcRs, maintaining immune quiescence to achieve a finely orchestrated immune response. The removal of sialic acid and galactose residues dramatically alters the physiological function of IgGs, and alterations of Ig glycosylation have been associated with several autoimmune disorders. However, Ig glycosylation has not been extensively studied in autoimmune cholangitis.

The CD137 Ligand Is Important for Type 1 Diabetes Development but Dispensable for the Homeostasis of Disease-Suppressive CD137 FOXP3 Regulatory CD4 T Cells.

CD137 modulates type 1 diabetes (T1D) progression in NOD mice. We previously showed that CD137 expression in CD4 T cells inhibits T1D, but its expression in CD8 T cells promotes disease development by intrinsically enhancing the accumulation of β-cell-autoreactive CD8 T cells. CD137 is expressed on a subset of FOXP3 regulatory CD4 T cells (Tregs), and CD137 Tregs are the main source of soluble CD137.

Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy.

The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome.

Soluble CD137 Ameliorates Acute Type 1 Diabetes by Inducing T Cell Anergy.

We show here that soluble CD137 (sCD137), the alternately spliced gene product of , effectively treats acute type 1 diabetes (T1D) in nonobese diabetic (NOD) mice. sCD137 significantly delayed development of end-stage disease, preserved insulin+ islet beta cells, and prevented progression to end-stage T1D in some mice. We demonstrate that sCD137 induces CD4+ T cell anergy, suppressing antigen-specific T cell proliferation and IL-2/IFN-γ secretion.

Locally and globally optimal configurations of N particles on the sphere with applications in the narrow escape and narrow capture problems.

Determination of optimal arrangements of N particles on a sphere is a well-known problem in physics. A famous example of such is the Thomson problem of finding equilibrium configurations of electrical charges on a sphere. More recently, however, similar problems involving other potentials and nonspherical domains have arisen in biophysical systems.

Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4 T cells.

Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver homeostasis. How liver-resident NK cells participate in autoimmune cholangitis remains unclear. Here, we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model, NK cell-deficient (Nfil3) mice, adoptive transfer and in vivo antibody-mediated NK cell depletion.

Proteomic analysis reveals distinctive protein profiles involved in CD8 T cell-mediated murine autoimmune cholangitis.

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver, and T cells are critical drivers in this process. However, little is known about the regulation of their functional behavior during disease development. We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis (PBC).

A Novel Mutation Interacts with the Nonobese Diabetic Genetic Background To Cause Autoimmune Cholangitis.

We previously reported that NOD.c3c4 mice develop spontaneous autoimmune biliary disease (ABD) with anti-mitochondrial Abs, histopathological lesions, and autoimmune T lymphocytes similar to human primary biliary cholangitis. In this article, we demonstrate that ABD in NOD.