Coexistence of hexatic and isotropic phases in two-dimensional Yukawa systems

We have performed Brownian dynamics simulations on melting of two-dimensional colloidal crystal in which particles interact with Yukawa potential. The pair correlation function and bond-orientational correlation function was calculated in the Yukawa system. An algebraic decay of the bond orientational correlation function was observed. By ruling out the coexistence region, only a unstable hexatic phase was found in the Yukawa systems. But our work shows that the melting of the Yukawa systems is a two-stage melting not consist with the KTHNY theory and the isotropic liquid and the hexatic phase coexistence region was found. Also we have studied point defects in two-dimensional Yukawa systems.Comment: 9 pages, 8 figures. any comments are welcom

A mathematical model shows macrophages delay staphylococcus aureus replication, but limitations in microbicidal capacity restrict bacterial clearance

S. aureus is a leading cause of bacterial infection. Macrophages, the first line of defence in the human immune response, phagocytose and kill S. aureus but the pathogen can evade these responses. Therefore, the exact role of macrophages is incompletely defined. We develop a mathematical model of macrophage - S. aureus dynamics, built on recent experimental data. We demonstrate that, while macrophages may not clear infection, they significantly delay its growth and potentially buy time for recruitment of further cells. We find that macrophage killing is a major obstacle to controlling infection and ingestion capacity also limits the response. We find bistability such that the infection can be limited at low doses. Our combination of experimental data, mathematical analysis and model fitting provide important insights in to the early stages of S. aureus infections, showing macrophages play an important role limiting bacterial replication but can be overwhelmed with large inocula

Experimental evidence that local interactions select against selfish behaviour

How social behaviours evolve remains one of the most debated questions in evolutionary biology. An important theoretical prediction is that when organisms interact locally due to limited dispersal or strong social ties, the population structure that emerges may favour cooperation over antagonism. We carry out an experimental test of this theory by directly manipulating population spatial structure in an insect laboratory model system and measuring the impact on the evolution of the extreme selfish behaviour of cannibalism. We show that, as predicted by the theory, Indian meal moth larvae that evolved in environments with more limited dispersal are selected for lower rates of cannibalism. This is important because it demonstrates that local interactions select against selfish behaviour. Therefore, the ubiquitous variation in population structure that we see in nature is a simple mechanism that can help to explain the variation in selfish and cooperative behaviours that we see in nature

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in Giant Cell Arteritis

OBJECTIVES: Giant Cell Arteritis (GCA) is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with [18F]FDG-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA. METHODS: Immunohistochemical detection of PKM2 was performed on inflamed (n = 12) and non-inflamed (n = 4) TABs from GCA patients and non-GCA (n = 9) patients. Dimeric PKM2 levels were assessed in plasma of GCA patients (n = 44), age-matched healthy controls (HC, n = 41), metastatic melanoma patients (n = 7) and infection controls (n = 11). CRP, ESR and macrophage markers calprotectin and YKL-40 were correlated with plasma PKM2 levels. To detect the cellular source of plasma PKM2 in tissue, double immunofluorescence staining was performed on inflamed GCA TABs. [18F]FDG-PET scans of 23 GCA patients were analyzed and maximum standard uptake values (SUVmax) and target to background ratios (TBR) were calculated. RESULTS: PKM2 is abundantly expressed in TABs of GCA patients. Dimeric PKM2 plasma levels were elevated in GCA and correlated with CRP, ESR, calprotectin, and YKL-40 levels. Elevated plasma PKM2 levels were downmodulated by GC-treatment. PKM2 was detected in both macrophages and T cells at the site of vascular inflammation. Circulating PKM2 levels correlated with average TBR PET scores. CONCLUSION: Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring

Cytokine producing B-cells and their capability to polarize macrophages in giant cell arteritis

OBJECTIVE: The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines.METHODS: The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro.RESULTS: The presence of IL-6, GM-CSF, TNFα, IFNγ, LTβ and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1β, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells.CONCLUSION: B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.</p

Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica

BACKGROUND: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. METHODS: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. RESULTS: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. CONCLUSION: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02754-5

The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. Objectives: We undertook a systematic review and meta-analysis, to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non-breath based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. Methods: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. Results: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I2 of 93.4% (p<0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. Conclusions: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role

Hereditary and acquired transthyretin-mediated amyloidosis

We describe three cases, two 70-year-old males with mainly cardiac symptoms and a 34-year-old male with gastro-intestinal and neurologic symptoms. Each patient was shown to have a distinctive type of transthyretin-mediated amyloidosis (ATTR). ATTR amyloidosis is a life-threatening disease characterised by the extracellular deposition of pathogenic transthyretin (TTR). A distinction is made between hereditary ATTR (ATTRv), in case of a pathogenic TTR mutation, and the acquired wild-type ATTR (ATTRwt). The prevalence of ATTR amyloidosis is probably underestimated. The variety of symptoms means that patients often visit several specialists, resulting in an average diagnostic delay of two to three years. Because of the development of new therapeutic possibilities, early diagnosis becomes more important to allow initiation of therapy at an early stage of the disease. Family members should be screened and asymptomatic carriers should undergo follow-up.</p