Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.     

The mechanics of contentious politics: an agent-based modeling approach

ABSTRACT

“Contentious politics” has become the main label to define a wide range of previously separated fields of research encompassing topics such as collective action, radicalization, armed insurgencies, and terrorism. Over the past two decades, scholars have tried to bring these various strands together into a unified field of study. In so doing, they have developed a methodology to isolate and analyze the common social and cognitive mechanisms underlying several diverse historical phenomena such as “insurgencies,” “revolutions,” “radicalization,” or “terrorism.” A multidisciplinary approach was adopted open to contributions from diverse fields such as economics, sociology, and psychology. The aim of this paper is to add to the multidisciplinarity of the field of Contentious Politics (CP) and introduce the instruments of Agent-Based Modeling and network game-theory to the study of some fundamental mechanisms analyzed within this literature. In particular, the model presented in this paper describes the dynamics of one process, here defined as “the radicalization of politics,” and its main underlying mechanisms. Their mechanics are analyzed in diverse social contexts differentiated by the values of four parameters: the extent of repression, inequality, social tolerance, and interconnectivity. The model can be used to explain the basic dynamics underlying different phenomena such as the development of radicalization, populism, and popular rebellions. In the final part, different societies characterized by diverse values of the aforementioned four parameters are tested through Python simulations, thereby offering an overview of the different outcomes that the mechanics of our model can shape according to the contexts in which they operate.     

Uncountable graphs with all their vertices in one face

Summary In 1967, Chartrand and Harary characterized finite outer-planar graphs, and Wagner studied uncountable graphs admitting a planar embedding. We continue this research for those outer-S graphs in surfaces S by studying uncountable graphs admitting S-embeddings with all their vertices in the same face (namely, outer-S embeddings).     

A new Cu(II) three-dimensional network with 4,4′-oxybis benzoic acid: structural diversity,EPR, and magnetism

The copper derivative {[Cu₄(oba)₄(H₂O)₄]?H₂O}_n (1) has been hydro(solvo)thermally synthesized by combining flexible 4,4′-oxybis benzoic acid (oba) and divalent copper nitrate. As a result of the potential coordination modes of carboxylate oxygens from the oba ligand, the aforementioned complex leads to the formation of an interesting 3D framework, as evidenced by single-crystal X-ray diffractometry. Concerning the topology in 1, the dimers [Cu₂C₄O₈] are nodes of a 5-fold 4-connected uninodal net of the type lvt, with point symbol {4².8⁴} and vertex symbol [4.4.8₄.8₄.8₈.8₈]. The encapsulation of the copper coordination polymer displays a moderate luminescent property. On temperature-dependent magnetic study, it reveals that the magnetic behaviour of 1 can be associated to a strong antiferromagnetic coupling between the two Cu(II) ions.     

The safety assessment of herbals with a new and ethical approach

The increasing use of plant medicines (herbals) in Europe needs a shared methodology to determine the toxicity and the daily exposure level to these drugs. For this reason, the European regulatory agencies have undertaken a study that could meet popular uses and toxicological research in different countries of the Union. Here we list some examples of the most used herbal drug classes and we propose a decision-making process based on their characteristics, their content in active principles and on the basis of the present scientific pharmacological and toxicological literature. The proposed decision tree actually makes easier for the assessor to quickly and accurately evaluate the accredited indexes for risk and toxicity assessment based on the preclinical literature data and using the correct classification that some of them may have because they are already present in medicinal products or used as food.