On the peculiar nature of turbulence in planetary dynamos

Under the combined constraints of rapid rotation, sphericity, and magnetic field, motions in planetary cores get organized in a peculiar way. Classical hydrodynamic turbulence is not present, but turbulent motions can take place under the action of the buoyancy and Laplace forces. Laboratory experiments, such as the rotating spherical magnetic Couette DTS experiment in Grenoble, help us understand what motions take place in planetary core conditions.Comment: in press in Compte Rendu de l'Academie des Science

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Spread of psoriasiform inflammation to remote tissues is restricted by the atypical chemokine receptor ACKR2

Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo, is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The membrane-bound psoriasis associated atypical chemokine receptor ACKR2 binds, internalises and degrades most pro-inflammatory CC-chemokines. Here we investigate the role of ACKR2 in limiting the spread of cutaneous psoriasiform inflammation to sites that are remote from the primary lesion.  Circulating factors capable of regulating ACKR2 function at remote sites were identified and examined using a combination of clinical samples, relevant primary human cell cultures, in vitro migration assays and the imiquimod-induced model of psoriasiform skin inflammation. Localised inflammation and IFN together upregulate ACKR2 in remote tissues, protecting them from the spread of inflammation. ACKR2 controls inflammatory T-cell chemotaxis and positioning within the skin, preventing an epidermal influx that is associated with lesion development. Our results have important implications for our understanding of how spatial restriction is imposed on the spread of inflammatory lesions, and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases

Forecasting yearly geomagnetic variation through sequential estimation of core low and magnetic diffusion

Earth’s internal magnetic field is generated through motion of the electrically conductive iron-alloy fluid comprising its outer core. Temporal variability of this magnetic field, termed secular variation (SV), results from two processes: one is the interaction between core fluid motion and the magnetic field, the other is magnetic diffusion. As diffusion is widely thought to take place over relatively long, millennial time scales, it is common to disregard it when considering yearly to decadal field changes; in this frozen-flux approximation, core fluid motion may be inferred on the core–mantle boundary (CMB) using observations of SV at Earth’s surface. Such flow models have been used to forecast variation in the magnetic field. However, recent work suggests that diffusion may also contribute significantly to SV on short time scales provided that the radial length scale of the magnetic field structure within the core is sufficiently short. In this work, we introduce a hybrid method to forecast field evolution that considers a model based on both a steady flow and diffusion, in which we adopt a two-step process: first fitting the SV to a steady flow, and then fitting the residual by magnetic diffusion. We assess this approach by hindcasting the evolution for 2010–2015, based on fitting the models to CHAOS-6 using time windows prior to 2010. We find that including diffusion yields a reduction of up to 25% in the global hindcast error at Earth’s surface; at the CMB this error reduction can be in excess of 77%. We show that fitting the model over the shortest window that we consider, 2009–2010, yields the lowest hindcast error. Based on our hindcast tests, we present a candidate model for the SV over 2020–2025 for IGRF-13, fit over the time window 2018.3–2019.3. Our forecasts indicate that over the next decade the axial dipole will continue to decay, reversed-flux patches will increase in both area and intensity, and the north magnetic (dip) pole will continue to migrate towards Siberia

role of next generation sequencing technologies in personalized medicine

Following the completion of the Human Genome Project in 2003, research in oncology has progressively focused on the sequencing of cancer genomes, with the aim of better understanding the genetic basis of oncogenesis and identifying actionable alterations. The development of next-generation-sequencing (NGS) techniques, commercially available since 2006, allowed for a cost- and time-effective sequencing of tumor DNA, leading to a "genomic era" of cancer research and treatment. NGS provided a significant step forward in Personalized Medicine (PM) by enabling the detection of somatic driver mutations, resistance mechanisms, quantification of mutational burden, germline mutations, which settled the foundation of a new approach in cancer care. In this chapter, we discuss the history, available techniques, and applications of NGS in oncology, with a particular referral to the PM approach and the emerging role of the research field of pharmacogenomics

Psoriasis: Classical vs. Paradoxical. The Yin-Yang of TNF and Type I Interferon.

Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/T &lt;sub&gt;H&lt;/sub&gt; 17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory diseases such as psoriasis. Although being highly effective in psoriasis treatment, anti-TNFs can themselves induce psoriasis-like skin lesions, a side effect called paradoxical psoriasis. In this review, we provide a comprehensive look at the different cellular and molecular players involved in classical plaque psoriasis and contrast its pathogenesis to paradoxical psoriasis, which is clinically similar but immunologically distinct. Classical psoriasis is a T-cell mediated autoimmune disease driven by TNF, characterised by T-cells memory, and a relapsing disease course. In contrast, paradoxical psoriasis is caused by the absence of TNF and represents an ongoing type-I interferon-driven innate inflammation that fails to elicit T-cell autoimmunity and lacks memory T cell-mediated relapses

Autoimmune aspects of psoriasis: Heritability and autoantigens

Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs. It concludes that disease-associated HLA alleles account for both missing heritability and autoimmune mechanisms by facilitating tissue-specific autoimmune responses through autoantigen presentation. (C) 2017 The Author. Published by Elsevier B.V