Adaptive Immune Responses in Primary Cutaneous Sarcoidosis

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis

Archaeobotanical evidence of plant food consumption among early farmers (5700-4500 BC) in the Western Mediterranean region

Les plantes domestiquées, les plantes sauvages cueillies et les plantes cultivées qui n’étaient peut-être pas entièrement domestiquées (par exemple, le pavot), faisaient partie intégrante du régime alimentaire du Néolithique. Des données provenant de 65 sites datés du Néolithique ancien (5800-4500 cal. BC) et situés entre le Nord-Est de la péninsule Ibérique et la plaine du Pô sont utilisées pour illustrer les choix des agriculteurs dans les assemblages de cultures et les activités de cueillette de plantes. Nous concluons que la consommation de nourriture végétale était très diversifiée au Néolithique, impliquant des céréales cultivées, des légumineuses et des plantes oléagineuses ainsi que des niveaux variables de ressources cueillies, en fonction des conditions environnementales

Textiles, basketry and cordage from the Early Neolithic settlement of La Marmotta, Lazio

Archaeological investigation of Circum-Alpine lake, or pile, dwellings has afforded unprecedented insight into Neolithic and Bronze Age societies. The discovery in 1989 of a submerged settlement near Rome added an early (eighth millennium BP) geographical outlier to this distribution. Two decades of excavation at La Marmotta have identified more than a dozen dwellings and an enormous assemblage of organic remains. Here, the authors present an overview of the textiles, basketry and cordage recovered, and the tools used to manufacture them. The assemblage paints a more complete picture of the technological expertise of Neolithic societies and their ability to exploit and process plant materials to produce a wide range of crafts

MxA mRNA quantification and disability progression in interferon beta-treated Multiple Sclerosis patients

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy

Multiproxy study of 7500-year-old wooden sickles from the Lakeshore Village of La Marmotta, Italy

[EN] The lakeshore site of La Marmotta is one of the most important Early Neolithic sites of Mediterranean Europe. The site is famous for the exceptional preservation of organic materials, including numerous wooden artefacts related to navigation, agriculture, textile production, and basketry. This article presents interdisciplinary research on three of the most complete and well‑preserved sickles recovered from the site, yet unpublished. All the components of the tools are analysed: the stone inserts, the wooden haft and the adhesive substances used to fix the stones inside the haft. Our innovative methodology combines use‑wear and microtexture analysis of stone tools through confocal microscopy, taxonomical and technological analysis of wood, gas chromatography–mass spectrometry analysis of the adhesive substances, and pollen, non‑pollen palynomorphs, and phytolith analysis of the remains incorporated within the adhesive. This multiproxy approach provides a significant insight into the life of these tools, from their production to their use and abandonment, providing evidence of the species of harvested plants and the conditions of the field during the harvesting