Overexpression of the ubiquitin-editing enzyme A20 in the brain lesions of Multiple Sclerosis patients: moving from systemic to central nervous system inflammation

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) in which inflammation plays a key pathological role. Recent evidences showed that systemic inflammation induces increasing cell infiltration within meninges and perivascular spaces in the brain parenchyma, triggering resident microglial ad astrocytic activation. The anti-inflammatory enzyme A20, also named TNF associated protein 3 (TNFAIP3), is considered a central gatekeeper in inflammation and peripheral immune system regulation through the inhibition of NF-kB. The TNFAIP3 locus is genetically associated to MS and its transcripts is down-regulated in blood cells in treatment-naive MS patients. Recently, several evidences in mouse models have led to hypothesize a function of A20 also in the CNS. Thus, here we aimed to unveil a possible contribution of A20 to the CNS human MS pathology. By immunohistochemistry/immunofluorescence and bio-molecular techniques on post-mortem brain tissue blocks obtained from control cases (CC) and progressive MS cases, we demonstrated that A20 is present in CC brain tissues in both white matter (WM) regions, mainly in few parenchymal astrocytes, and in grey matter (GM) areas, in some neuronal populations. Conversely, in MS brain tissues, we observed increased expression of A20 by perivascular infiltrating macrophages, resident activated astrocytes and microglia in all the active and chronic active WM lesions. A20 was highly-expressed also in the majority of active cortical lesions compared to the neighboring areas of normal-appearing grey matter (NAGM) and control GM, particularly by activated astrocytes. We demonstrated increased A20 expression in the active MS plaques, particularly in macrophages and resident astrocytes, suggesting a key role of this molecule in chronic inflammation

Assessment of building behavior in slow-moving landslide-affected areas through DInSAR data and structural analysis

Slow-moving landslides are a natural hazard which affects wide areas in the world and often are cause of significant damage to structures and infrastructures. Analysis of landslide evolution and of their interaction with existing man-made structures plays a key role in risk prevention and mitigation activities. To this purpose, a considerable interest towards innovative approaches has grown among the scientific community and land management institutions. In this work, Synthetic Aperture Radar data acquired by C-band and X-band sensors, combined with numerical analyses, have been successfully applied as a tool to detect spatial and temporal landslide-induced effects, in terms of deformations and structural behavior of a building affected by ground instability. Such approach has been applied to Moio della Civitella urban settlement (Salerno province, Italy), whose whole territory is interested by several slow-moving landslides. In detail, performance of a masonry building aggregate and the efficacy of restoration works have been investigated through an integrated assessment of displacement time-series pre- and post-repair intervention, and structural analysis performed with numerical code. Historical DInSAR data have permitted firstly the interpretation of building displacement time-series corresponding to pre- and post-works configurations; subsequently, the analysis of interpolated interferometric products has allowed to define gradient maps of vertical and horizontal displacements and to identify part of aggregate which can suffer a greater susceptibility to damage as a consequence of deformation gradients. Finally, the comparison of satellite and numerical data showed a substantial agreement with local failures and damage surveyed, thus confirming the capability of DInSAR technique to investigate building performance where no in situ displacement measurements were available.Research funded by the Campania Region through Regional Law n. 5/2002, year 2008 – Project “La pericolosità delle frane intermittenti in formazioni strutturalmente complesse; analisi comparata dei parametri geologici, mineralogici e geotecnici” (CUP_E64G08000060002) – Scientific manager: prof. Domenico Calcaterra. Part of this work was partially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the State Agency of Research (AEI) and the European Funds for Regional Development (FEDER) under projects TEC2017-85244-C2-1-P and TIN2014-55413-C2-2-P and the Spanish Ministry of Education, Culture and Sport under project PRX17/00439

Pretest. Un approccio cognitivo

Il volume illustra l’intervista cognitiva, una tecnica di pretest dei que-stionari oggi largamente affermata tra i ricercatori sociali. Nel primo capitolo si propone una ricostruzione storica del dibattito sul pretest e viene illustrata una tipologia delle tecniche più diffuse. Il secondo ca-pitolo è prevalentemente dedicato al Cognitive Aspects of Survey Me-thodology (CASM), movimento sorto nei primi anni ottanta per pro-muovere la collaborazione tra psicologi cognitivi e ricercatori sociali, i cui contributi teorici ed empirici hanno dato impulso all’ideazione della tecnica oggetto di questo libro. L’ultimo capitolo illustra l’intervista co-gnitiva e le modalità specifiche con cui la tecnica mira ad indagare i processi mentali che gli intervistati mettono in atto quando rispondono alle domande di un questionario. Le riflessioni e le ricerche (nostre e di altri autori) sull’intervista cognitiva sono sempre presentate con spirito critico, al fine di mettere in luce le potenzialità e i limiti della tecnica

Cognitive Interviewing to Pretest Attitude Questions

The purpose of this paper is to assess the potentials and the limits of the cognitive interview to pretest attitude questions. The paper begins with a preface describing what cognitive interview is and what are its theoretical roots. Then we take part in the debate on the cognitive interview and we discuss the strengths and weakness of its strategies. Lastly, we present the design and the findings of a methodological research on the effectiveness of the two strategies typical of the cognitive interview – the think-aloud and the verbal probing – in order to pretest attitude questions

Lʼauto-valutazione della produzione di una comunità scientifica: una proposta metodologica

In this paper we present a self-evaluation model of the research production of a scientific community. This model is based on a case study: an analysis of the publications of the academic staff at the Department of Communication and Social Research (La Sapienza, University of Rome) from 2011 to 2014. In the first part of the paper, we describe the publications production from a quantitative perspective; then, we introduce more qualitative aspects considering an index of editorial ranking of the publications. In both sections, the synchronic analysis is combined with a diachronic analysis, in order to identify trends. We believe that this model will be useful both for the research institutes to evaluate outputs and outcomes of their policies, and for the researchers to benchmark their publication style against the scientific production of their communities

TNFAIP3 Deficiency Affects Monocytes, Monocytes-Derived Cells and Microglia in Mice

The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. Single nucleotide polymorphisms in TNFAIP3 locus have been associated to autoimmune inflammatory disorders, including Multiple Sclerosis (MS). Previously, we reported a TNFAIP3 down-regulated gene expression level in blood and specifically in monocytes obtained from treatment-naïve MS patients compared to healthy controls (HC). Myeloid cells exert a key role in the pathogenesis of MS. Here we evaluated the effect of specific TNFAIP3 deficiency in myeloid cells including monocytes, monocyte-derived cells (M-MDC) and microglia analyzing lymphoid organs and microglia of mice. TNFAIP3 deletion is induced using conditional knock-out mice for myeloid lineage. Flow-cytometry and histological procedures were applied to assess the immune cell populations of spleen, lymph nodes and bone marrow and microglial cell density in the central nervous system (CNS), respectively. We found that TNFAIP3 deletion in myeloid cells induces a reduction in body weight, a decrease in the number of M-MDC and of common monocyte and granulocyte precursor cells (CMGPs). We also reported that the lack of TNFAIP3 in myeloid cells induces an increase in microglial cell density. The results suggest that TNFAIP3 in myeloid cells critically controls the development of M-MDC in lymphoid organ and of microglia in the CNS