Data-based dynamic compartment model: Modeling of E. coli fed-batch fermentation in a 600 m3 bubble column.

Mathematical modeling is a powerful and inexpensive approach to provide a quantitative basis for improvements that minimize the negative effects of bioreactor heterogeneity. For a model to accurately represent a heterogeneous system, a flow model that describes how mass is channeled between different zones of the bioreactor volume is necessary. In this study, a previously developed compartment model approach based on data from flow-following sensor devices was further developed to account for dynamic changes in volume and flow rates and thus enabling simulation of the widely used fed-batch process.

High Interferon Signature Leads to Increased STAT1/3/5 Phosphorylation in PBMCs From SLE Patients by Single Cell Mass Cytometry.

The establishment of an "interferon (IFN) signature" to subset SLE patients on disease severity has led to therapeutics targeting IFNα. Here, we investigate IFN signaling in SLE using multiplexed protein arrays and single cell cytometry by time of flight (CyTOF). First, the IFN signature for SLE patients (n=81) from the Stanford Lupus Registry is determined using fluidigm qPCR measuring 44 previously determined IFN-inducible transcripts.

[Hypothalamic-pituitary dysfunction in a patient with neurosarcoidosis].

This is a case report of a 64-year-old man with pulmonary sarcoidosis also affecting the joints. He was admitted to an emergency department following 21 days of fatigue, visual disturbances and headache. Initial blood tests revealed hypothalamic-pituitary dysfunction including acute adrenal insufficiency, and an MRI scan of the cerebrum showed a neurosarcoidosis tumour involving the hypothalamus-pituitary gland.

Flow-following sensor devices: A tool for bridging data and model predictions in large-scale fermentations.

Production-scale fermentation processes in industrial biotechnology experience gradients in process variables, such as dissolved gases, pH and substrate concentrations, which can potentially affect the production organism and therefore the yield and profitability of the processes. However, the extent of the heterogeneity is unclear, as it is currently a challenge at large scale to obtain representative measurements from different zones of the reactor volume. Computational fluid dynamics (CFD) models have proven to be a valuable tool for better understanding the environment inside bioreactors.

Effects of Anti-TNF Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease.

T helper 17 (Th17) cells produce interleukin (IL) 17-A. In addition, Th17 cells produce IL-21 and IL-22. Th17 cells have a disease-promoting role in Crohn's disease (CD).

Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer.

Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer.

STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes.

The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently JAK/STAT inhibitors have shown promising results in psoriasis treatment. The present study aimed to characterize the role of STAT2 in psoriasis. We demonstrated an increased expression of STAT2 and an increased level of phosphorylated/activated STAT2 in lesional compared with nonlesional psoriatic skin.

Follicular T helper cells and IL-21 in rheumatic diseases.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life.

A disintegrin and metalloprotease-17 and galectin-9 are important regulators of local 4-1BB activity and disease outcome in rheumatoid arthritis.

Objective: Co-stimulatory T cell cytokines are important in the progression of RA. This study investigates the interplay between 4-1BB, a disintegrin and metalloprotease-17 (ADAM17) and galectin-9 (Gal-9) in RA.

Methods: Stimulated mononuclear cells from patients with chronic RA (n = 12) were co-incubated with tissue inhibitor of metalloproteinase, 4-1BB ligand and Gal-9.

Development of Th17-Associated Interstitial Kidney Inflammation in Lupus-Prone Mice Lacking the Gene Encoding STAT-1.

Objective: Type I interferon (IFN) signaling is a central pathogenic pathway in systemic lupus erythematosus (SLE), and therapeutics targeting type I IFN signaling are in development. Multiple proteins with overlapping functions play a role in IFN signaling, but the signaling events downstream of receptor engagement are unclear. This study was undertaken to investigate the roles of the type I and type II IFN signaling components IFN-α/β/ω receptor 2 (IFNAR-2), IFN regulatory factor 9 (IRF-9), and STAT-1 in a mouse model of SLE.

Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus.

Introduction: Interleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE.

Methods: The signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells.

Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis.

Introduction: OX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA).

Methods: Soluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37).

CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic 'window of opportunity'.

Introduction: A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis.

Highest frequencies of interleukin-22-producing T helper cells in alcoholic hepatitis patients with a favourable short-term course.

Background: Alcoholic hepatitis (AH) has a severe prognosis due to hepatic inflammatory injury. The cytokine interleukin-22 (IL-22) is reported to exert anti-apoptotic and proliferative effects, but IL-22 has not been studied during the course of AH. IL-22 is mainly produced by CD4(+) (helper) T cells, including Th17 cells.

Increased levels of circulating Th17 cells in quiescent versus active Crohn's disease.

Background And Aims: Th17 cells, a subset of CD4+ T cells that produce interleukin (IL)-17A, IL-17F, IL-21, IL-22, IL-26, and the chemokine CCL20 are critically involved in the mucosal inflammation observed in Crohn's disease (CD). However, their role as mediators of inflammation in CD has been questioned by a recent clinical trial in which anti-IL-17A (secukinumab) treatment was ineffective. Besides being pro-inflammatory, Th17-related cytokines mediate mucosal protective functions.

Thermal and acid denaturation of bovine lens α-crystallin.

The chaperone-like protein α-crystallin is a ∼35 subunit hetero-oligomer consisting of αA and αB subunits in a 3:1 molar ratio and has the function of maintaining eye lens transparency. We studied the thermal denaturation of α-crystallin by differential scanning calorimetry (DSC), circular dichroism (CD), and dynamic light scattering (DLS) as a function of pH. Our results show that between pH 7 and 10 the protein undergoes a reversible thermal transition.

Increased plasma levels of IL-21 and IL-23 in spondyloarthritis are not associated with clinical and MRI findings.

We have investigated the role of the Th17-related cytokines interleukin-17A (IL-17A), IL-21, and IL-23 in spondyloarthritis (SpA) by examining their association with disease activity and magnetic resonance imaging (MRI) findings in patients with SpA (n = 80). Furthermore, to investigate the cellular origins of the cytokines, paired mononuclear cells from blood and synovial fluid were examined for the expression of IL-17A, IL-21, and IL-23R using multicolor flow cytometry. Both IL-21 and IL-23 levels were increased in plasma from SpA patients compared with healthy volunteers (P < 0.

Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis.

Objective: To investigate the levels of the T helper (Th)17-related cytokines interleukin 17A (IL-17A), IL-21, and IL-23 and their association with disease activity in rheumatoid arthritis (RA).

Methods: In a longitudinal sample set from patients with early RA (< 6 months; n = 40), we measured the plasma cytokine levels of IL-17A, IL-21, and IL-23 and analyzed for correlation with disease activity in 28 joints (Disease Activity Score 28-joint count; DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and total Sharp score (TSS). In a transverse sample set of patients with chronic RA (> 8 years), using paired peripheral blood mononuclear cells and synovial fluid mononuclear cells, we investigated the cellular expression of IL-17A, IL-21, and IL-23R.

The molecular chaperone alpha-crystallin as an excipient in an insulin formulation.

Purpose: To investigate insulin fibrillation under accelerated stress conditions in the presence of a novel excipient, the molecular chaperone alpha-crystallin, in comparison with common excipients.

Methods: To induce fibrillation, recombinant human insulin (0.58 mg ml(-1)) formulations without excipient or with bovine alpha-crystallin (0.

Elution behavior of insulin on high-performance size exclusion chromatography at neutral pH.

The pharmacopoeia protocol for HP-SEC of insulin, using an acidic non-physiological eluent, does not represent insulin's association state in the formulation. This study aimed to evaluate insulin's elution behavior in HP-SEC in a "physiological" (aqueous, neutral pH) eluent, using on-line UV absorption and multi-angle laser light scattering detection. The effect of insulin concentration and association state in the formulation (monitored by circular dichroism) and eluent composition (zinc ion, arginine) on its elution behavior was assessed.

The chaperone-like protein alpha-crystallin dissociates insulin dimers and hexamers.

The protein alpha-crystallin, a member of the small heat shock protein family, has the ability to prevent aggregation of partially denatured proteins, an effect demonstrated both in vivo and in vitro. In this work, we have probed the apparent thermal destabilization of bovine insulin by alpha-crystallin, using differential scanning calorimetry, near-UV circular dichroism, and intrinsic fluorescence spectroscopy. The thermal denaturation of insulin, followed by differential scanning calorimetry, is greatly affected by the presence of alpha-crystallin.

The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle.

The bacterium Vibrio cholerae, the cause of the diarrhoeal disease cholera, has its genome divided between two chromosomes, a feature uncommon for bacteria. The two chromosomes are of different sizes and different initiator molecules control their replication independently. Using novel methods for analysing flow cytometry data and marker frequency analysis, we show that the small chromosome II is replicated late in the C period of the cell cycle, where most of chromosome I has been replicated.