MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.     

Influence of ultimate pH on biochemistry and quality of Longissimus lumborum steaks from Nellore bulls during ageing

Ultimate pH (pH_u) is an indicator that influences post-mortem meat quality. We studied physiological and biochemical changes of steaks obtained from Nellore bulls (Bos indicus) during post-mortem ageing. To this, Longissimus lumborum (LL) muscles were classified into three groups: Normal-pH_u (≤5.79), Intermediate-pH_u (5.80–6.29) and High-pH_u (≥6.30) groups, portioned into steaks, vacuum packaged and matured at 2 °C for 0, 7, 14, 21 and 28 days. High-pH_u steaks exhibited impaired colour stability and were darker compared to the other groups. High- and Normal-pH_u steaks showed improved tenderness and myofibrillar fragmentation linked to proteolysis. Intermediate-pH_u steaks were associated with a lower meat tenderness and decreased collagen solubility. High-pH_u steaks retained a high pH during ageing and increased water-holding capacity. These findings provide evidence that highlight pH_u as a strategy for the classification of pH_u-dependent beef quality from Nellore bulls that can be adopted by the Brazilian meat industry.     

Anti-Trypanosoma cruzi Activity of Metabolism Modifier Compounds

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC₅₀ = 0.27 μmol L⁻¹) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.     

An Unprecedented Stimuli‐Controlled Single‐Crystal Reversible Phase Transition of a Metal–Organic Framework and Its Application to a Novel Method of Guest Encapsulation

The flexibility and unexpected dynamic behavior of a third‐generation metal–organic framework are described for the first time. The synthetic strategy is based on the flexibility and spherical shape of dipyridyl‐based carborane linkers that act as pillars between rigid Co/BTB (BTB: 1,3,5‐benzenetricarboxylate) layers, providing a 3D porous structure ( 1 ). A phase transition of the solid can be induced to generate a new, nonporous 2D structure ( 2 ) without any loss of the carborane linkers. The structural transformation is visualized by snapshots of the multistep single‐crystal‐to‐single‐crystal transformation by single‐crystal and powder X‐ray diffraction. Poor hydrogen bond acceptors such as MeOH, CHCl₃ or supercritical CO₂ induce such a 3D to 2D transformation. Remarkably, the transformation is reversible and the 2D phase 2 is further converted back into 1 by heating in dimethylformamide. The energy requirements involved in such processes are investigated using periodic density functional theory calculations. As a proof of concept for potential applications, encapsulation of C₆₀ is achieved by trapping this molecule during the reversible 2D to 3D phase transition, whereas no adsorption is observed by straight solvent diffusion into the pores of the 3D phase.     

A Kernel Search Matheuristic to Solve The Discrete Leader-Follower Location Problem

Networks and Spatial Economics - In the leader-follower, (r|p)-centroid or Stackelberg location problem, two players sequentially enter the market and compete to provide goods or services. This...