Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies.

Maackia amurensis seed lectin (MASL) ameliorates articular cartilage destruction and increases movement velocity of mice with TNFα induced rheumatoid arthritis.

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition.

American Association of Immunologists Recommendations for an Undergraduate Course in Immunology.

Identifying the "essential" components of an undergraduate immunology lecture course can be daunting because of the varying postgraduate pathways students take. The American Association of Immunologists Education Committee commissioned an Ad Hoc Committee, representing undergraduate, graduate, and medical institutions as well as the biotechnology community, to develop core curricular recommendations for teaching immunology to undergraduates. In a reiterative process involving the American Association of Immunologists teaching community, 14 key topics were identified and expanded to include foundational concepts, subtopics and examples, and advanced subtopics, providing a flexible list for curriculum development and avenues for higher-level learning.

Differential cellular composition of human palatine and pharyngeal tonsils.

Objective: The goal of this study was to gain a better understanding of the potential functional specialization of palatine and pharyngeal tonsils, by comparing their cellular composition in paired specimens from a large cohort of adenotonsillectomy patients.

Design: Resident B cell, T cell, dendritic cell, and stromal cell subsets were characterized using multicolor flow cytometry in palatine and pharyngeal tonsil specimens from 27 patients, age 2-34 years.

Results: Paired comparisons showed highly significant intra-individual differences in resident cell subsets of palatine and pharyngeal tonsils.

Animal models of rheumatoid pain: experimental systems and insights.

Severe chronic pain is one of the hallmarks and most debilitating manifestations of inflammatory arthritis. It represents a significant problem in the clinical management of patients with common chronic inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies. The functional links between peripheral inflammatory signals and the establishment of the neuroadaptive mechanisms acting in nociceptors and in the central nervous system in the establishment of chronic and neuropathic pain are still poorly understood, representing an area of intense study and translational priority.

Chronic exposure to tumor necrosis factor in vivo induces hyperalgesia, upregulates sodium channel gene expression and alters the cellular electrophysiology of dorsal root ganglion neurons.

The goal of these studies was to investigate the links between chronic exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF), hyperalgesia and the excitability of dorsal root ganglion (DRG) sensory neurons. We employed transgenic mice that constitutively express TNF (TNFtg mice), a well-established model of chronic systemic inflammation. At 6 months of age, TNFtg mice demonstrated increased sensitivity to both mechanical and thermal heat stimulation relative to aged-matched wild-type controls.

Brief Report: Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis Factor Restores Lymphatic Contractions, Repairs Lymphatic Vessels, and May Increase Monocyte/Macrophage Egress.

Objective: Recent studies have demonstrated that there is an inverse relationship between lymphatic egress and inflammatory arthritis in affected joints. As a model, tumor necrosis factor (TNF)-transgenic mice develop advanced arthritis following draining lymph node (LN) collapse, and loss of lymphatic contractions downstream of inflamed joints. It is unknown if these lymphatic deficits are reversible.

Increased numbers of CD23(+) CD21(hi) Bin-like B cells in human reactive and rheumatoid arthritis lymph nodes.

A unique population of CD23(+) CD21(high) B cells in inflamed nodes (Bin) has been shown to accumulate in lymph nodes (LNs) draining inflamed joints of TNF-transgenic (TNF-tg) mice. Bin cells contribute to arthritis flare in mice by distorting node architecture and hampering lymphatic flow, but their existence in human inflamed LNs has not yet been described. Here, we report the characterization of resident B-cell populations in fresh popliteal lymph nodes (PLNs) from patients with severe lower limb diseases (non-RA) and rheumatoid arthritis (RA) patients, and from banked, cryopreserved reactive and normal human LN single cell suspension samples.

The CD27-CD70 pathway and pathogenesis of autoimmune disease.

Objective: To critically examine current evidence regarding the role of the CD27-CD70 pathway in the pathophysiology of autoimmune disease with a focus on understanding the contributions of this pathway as a potential new therapeutic target for systemic lupus erythematosus and rheumatoid arthritis.

Methods: A PubMed search for articles was conducted using the following key words: ("CD27" OR "CD70") AND ("autoimmune disease" OR "systemic lupus erythematosus" OR "rheumatoid arthritis"). The search was limited to publications in English and included human and animal studies.

Effect of plate permeability on nonlinear stability of the asymptotic suction boundary layer.

The nonlinear stability of the asymptotic suction boundary layer is studied numerically, searching for finite-amplitude solutions that bifurcate from the laminar flow state. By changing the boundary conditions for disturbances at the plate from the classical no-slip condition to more physically sound ones, the stability characteristics of the flow may change radically, both for the linearized as well as the nonlinear problem. The wall boundary condition takes into account the permeability K̂ of the plate; for very low permeability, it is acceptable to impose the classical boundary condition (K̂=0).

TNF signals are dispensable for the generation of CD23+ CD21/35-high CD1d-high B cells in inflamed lymph nodes.

Tumor necrosis factor (TNF) is a key cytokine in rheumatoid arthritis (RA) pathogenesis, as underscored by the clinical effectiveness of TNF antagonists. While several of TNF's key targets in RA are well understood, its many pleiotropic effects remain to be elucidated. TNF-transgenic mice develop inflammatory-erosive arthritis associated with disruption of draining lymph node histology and function, and accumulation of B cells with unique phenotypic and functional features consistent with contribution to pathogenesis (B cells in inflamed nodes, Bin).

Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: a pilot, prospective study.

Background: TNF inhibitors have been used as a treatment for moderate to severe RA patients. However, reliable biomarkers that predict therapeutic response to TNF inhibitors are lacking. In this study, we investigated whether chemokines may represent useful biomarkers to predict the response to TNF inhibitor therapy in RA.

Unstable flow structures in the Blasius boundary layer.

Finite amplitude coherent structures with a reflection symmetry in the spanwise direction of a parallel boundary layer flow are reported together with a preliminary analysis of their stability. The search for the solutions is based on the self-sustaining process originally described by Waleffe (Phys. Fluids 9, 883 (1997)).

Spontaneous symmetry breaking of a hinged flapping filament generates lift.

Elastic filamentous structures found on swimming and flying organisms are versatile in function, rendering their precise contribution to locomotion difficult to assess. We show in this Letter that a single passive filament hinged on the rear of a bluff body placed in a stream can generate a net lift force without increasing the mean drag force on the body. This is a consequence of spontaneous symmetry breaking in the filament's flapping dynamics.

Peroxisome proliferator-activated receptor γ B cell-specific-deficient mice have an impaired antibody response.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ, a ligand-activated transcription factor, has important anti-inflammatory and antiproliferative functions, and it has been associated with diseases including diabetes, scarring, and atherosclerosis, among others. PPARγ is expressed in most bone marrow-derived cells and influences their function.

Efficacy of B cell depletion therapy for murine joint arthritis flare is associated with increased lymphatic flow.

Objective: B cell depletion therapy ameliorates rheumatoid arthritis by mechanisms that are incompletely understood. Arthritis flare in tumor necrosis factor (TNF)-transgenic mice is associated with efferent lymph node (LN) "collapse," triggered by B cell translocation into lymphatic spaces and decreased lymphatic drainage. The aim of this study was to examine whether the efficacy of B cell depletion therapy is associated with restoration of lymphatic drainage due to removal of obstructing nodal B cells.

On the infusion of a therapeutic agent into a solid tumor modeled as a poroelastic medium.

The direct infusion of an agent into a solid tumor, modeled as a spherical poroelastic material with anisotropic dependence of the tumor hydraulic conductivity upon the tissue deformation, is treated both by solving the coupled fluid/elastic equations, and by expressing the solution as an asymptotic expansion in terms of a small parameter, ratio between the driving pressure force in the fluid system, and the elastic properties of the solid. Results at order one match almost perfectly the solutions of the full system over a large range of infusion pressures. Comparison with experimental results is acceptable after the hydraulic conductivity of the medium is properly calibrated.

CD23+ CD21(high) CD1d(high) B cells in inflamed lymph nodes are a locally differentiated population with increased antigen capture and activation potential.

CD23(+)CD21(high)CD1d(high) B cells in inflamed nodes (Bin cells) accumulate in the lymph nodes (LNs) draining inflamed joints of the TNF-α-transgenic mouse model of rheumatoid arthritis and are primarily involved in the significant histological and functional LN alterations that accompany disease exacerbation in this strain. In this study, we investigate the origin and function of Bin cells. We show that adoptively transferred GFP(+) sorted mature follicular B (FoB) cells home preferentially to inflamed LNs of TNF-α-transgenic mice where they rapidly differentiate into Bin cells, with a close correlation with the endogenous Bin fraction.

CD23(+)/CD21(hi) B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with episodic flares in affected joints. However, how arthritic flare occurs only in select joints during a systemic autoimmune disease remains an enigma. To better understand these observations, we developed longitudinal imaging outcomes of synovitis and lymphatic flow in mouse models of RA, and identified that asymmetric knee flare is associated with ipsilateral popliteal lymph node (PLN) collapse and the translocation of CD23(+)/CD21(hi) B-cells (B-in) into the paracortical sinus space of the node.

Nonequilibrium thermodynamics and the optimal path to turbulence in shear flows.

We determine the initial condition on the laminar-turbulent boundary closest to the laminar state using nonlinear optimization for plane Couette flow. Resorting to the general evolution criterion of nonequilibrium systems we optimize the route to the statistically steady turbulent state, i.e.

Adaptation to continuous perturbation of balance: progressive reduction of postural muscle activity with invariant or increasing oscillations of the center of mass depending on perturbation frequency and vision conditions.

We investigated the adaptation of balancing behavior during a continuous, predictable perturbation of stance consisting of 3-min backward and forward horizontal sinusoidal oscillations of the support base. Two visual conditions (eyes-open, EO; eyes-closed, EC) and two oscillation frequencies (LF, 0.2 Hz; HF, 0.

Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor.

Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g., T and B lymphocytes) and functional compartments which is critical for immune function.

Rapid path to transition via nonlinear localized optimal perturbations in a boundary-layer flow.

Recent studies have suggested that in some cases transition can be triggered by some purely nonlinear mechanisms. Here we aim at verifying such an hypothesis, looking for a localized perturbation able to lead a boundary-layer flow to a chaotic state, following a nonlinear route. Nonlinear optimal localized perturbations have been computed by means of an energy optimization which includes the nonlinear terms of the Navier-Stokes equations.