The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes

Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs

Comparison of IFCC-calibrated HbA1c from laboratory and point of care testing systems

Objective: WHO, IDF and ADA recommend HbA1c ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA1c from several methods for research relating glycaemic markers.Research design and methods: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000®+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol).Results: median (IQ range) on IFCC SRM was 7.5% (6.8–8.4) (58(51–68) mmol/mol) HbA1c with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r2 = 0.984, p &lt; 0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r2 = 0.976, p &lt; 0.001 with a very small negative difference −0.04%(0.11) (−0.4(1.2) mmol/mol), r2 = 0.992, p &lt; 0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000®+ analyser −0.13%(0.28) (−1.4(3.1) mmol/mol), r2 = 0.955, p &lt; 0.001 and A1cNow+ cartridges −0.70%(0.67) (−7.7(7.3) mmol/mol), r2 = 0.699, p &lt; 0.001 (n = 113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration.Conclusions: small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA1c range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.</p

Policies, Political-Economy, and Swidden in Southeast Asia

For centuries swidden was an important farming practice found across the girth of Southeast Asia. Today, however, these systems are changing and sometimes disappearing at a pace never before experienced. In order to explain the demise or transitioning of swidden we need to understand the rapid and massive changes that have and are occurring in the political and economic environment in which these farmers operate. Swidden farming has always been characterized by change, but since the onset of modern independent nation states, governments and markets in Southeast Asia have transformed the terms of swiddeners’ everyday lives to a degree that is significantly different from that ever experienced before. In this paper we identified six factors that have contributed to the demise or transformation of swidden systems, and support these arguments with examples from China (Xishuangbanna), Laos, Thailand, Malaysia, and Indonesia. These trends include classifying swiddeners as ethnic minorities within nation-states, dividing the landscape into forest and permanent agriculture, expansion of forest departments and the rise of conservation, resettlement, privatization and commoditization of land and land-based production, and expansion of market infrastructure and the promotion of industrial agriculture. In addition we note a growing trend toward a transition from rural to urban livelihoods and expanding urban-labor markets

Simulation-based cheminformatic analysis of organelle-targeted molecules: lysosomotropic monobasic amines

Cell-based molecular transport simulations are being developed to facilitate exploratory cheminformatic analysis of virtual libraries of small drug-like molecules. For this purpose, mathematical models of single cells are built from equations capturing the transport of small molecules across membranes. In turn, physicochemical properties of small molecules can be used as input to simulate intracellular drug distribution, through time. Here, with mathematical equations and biological parameters adjusted so as to mimic a leukocyte in the blood, simulations were performed to analyze steady state, relative accumulation of small molecules in lysosomes, mitochondria, and cytosol of this target cell, in the presence of a homogenous extracellular drug concentration. Similarly, with equations and parameters set to mimic an intestinal epithelial cell, simulations were also performed to analyze steady state, relative distribution and transcellular permeability in this non-target cell, in the presence of an apical-to-basolateral concentration gradient. With a test set of ninety-nine monobasic amines gathered from the scientific literature, simulation results helped analyze relationships between the chemical diversity of these molecules and their intracellular distributions

Small-Scale Beef Cattle Production in East Java, Indonesia

Despite its small area and intensively cropped landscape, East Java accounts for 30% of Indonesia’s beef cattle population. About two million households draw on family labour to raise cattle in backyard sheds and small enclosures, largely for cash income. The paper reports on a study in two contrasting sites – irrigated lowlands and rainfed uplands – to explore the constraints facing cattle producers in these environments and possible means to enhance their production systems and incomes. In particular, the paper focuses on the issue of feed supply and the local market that has emerged for agricultural by-products (rice straw, maize stover, and legume residues) and planted forage grasses. The research shows that intensive cattle production can provide a viable pathway out of poverty, even for resource-poor households