Psoriasis : from transcriptome to miRNA function and biomarkers

Psoriasis is a chronic inflammatory, immune-mediated skin condition that affects in average 2 to 3% of the world population, phenotypically characterized by red and scaly plaques on the skin of affected patients. It is a multifactorial disorder, in which both genetic predisposition and environment play key roles. Psoriasis lesional skin is characterized by abnormal keratinocyte differentiation and proliferation, as well as dermal immune cell infiltration. Psoriasis is associated with several comorbidities, e.g. arthritis, however, currently no biomarkers exist that could be used to predict or identify these at an early stage. Many studies aimed to characterize the psoriasis transcriptome, but few studies have been focusing on elucidating the gene alterations in keratinocytes in this disease. In this thesis, we explored the transcriptomic landscape of epidermal cells from lesional and non-lesional skin of patients with psoriasis, as well as from healthy volunteers’ skin and investigated the biomarker-potential of circulating microRNAs. In our first study, we investigated the alterations of the protein-coding transcriptome in the psoriasis epidermal compartment. The separation of the epidermis from the dermis and sorting for CD45-neg cells allowed us to exclude dermal signatures including those from fibroblasts, endothelial cells, dendritic cells and T cells, but also from immune cells infiltrating the epidermis, known to populate at increased ratio the psoriasis lesional skin. We have identified biological pathways related to immune responses, cell cycle and keratinization involved in the epidermal alterations, as well as the enrichment and dominance of psoriasis-associated cytokine signatures. Moreover, we established that genetic variations associated with psoriasis may contribute to the keratinocyte transcriptomic changes in the disease. In our second study, we investigated the alterations of the non-protein-coding transcriptome in psoriasis and identified a set of long non-coding RNAs differentially expressed in psoriasis epidermal cells. Several had genomic localization overlapping psoriasis-associated SNPs, suggesting their potential implication in the genetic susceptibility to psoriasis. We validated the over-expression of the lncRNA LINC00958 in CD45-neg cells from psoriasis lesions compared to non-lesional and healthy skin and determined its expression in different skin cell types and subcellular localization. In our third study, we focused on psoriatic arthritis, the major psoriasis comorbidity, affecting about 1/3 of the patients with cutaneous psoriasis. In particular, we investigated the potential of circulating microRNAs as biomarkers for early diagnosis of psoriatic arthritis symptoms in patients with cutaneous psoriasis. We have identified two circulating microRNAs, let-7b-5p and miR-30e-5p, with significantly reduced levels in plasma-derived extracellular vesicles of patients with confirmed psoriatic arthritis, compared to cutaneous-only psoriasis patients. Finally, in our fourth study, we investigated the role and functions of miR-378a, previously found overexpressed in psoriasis lesional keratinocytes compared to non-lesional and healthy skin. In vivo, in a mouse model of psoriasis-like skin inflammation, the injection of miR-378a resulted in increased clinical signs of inflammation, increased skin thickness and number of proliferating cells in the epidermis. In vitro, in cultured primary human keratinocytes, miR-378a overexpression enhanced the expression of pro-inflammatory chemokines CXCL8/IL8 and CCL20, as well as reduction of NFKBIA proteins levels

The Pancreatic Islet Regulome Browser

The pancreatic islet is a highly specialized tissue embedded in the exocrine pancreas whose primary function is that of controlling glucose homeostasis. Thus, understanding the transcriptional control of islet-cell may help to puzzle out the pathogenesis of glucose metabolism disorders. Integrative computational analyses of transcriptomic and epigenomic data allows predicting genomic coordinates of putative regulatory elements across the genome and, decipher tissue-specific functions of the non-coding genome. We herein present the Islet Regulome Browser, a tool that allows fast access and exploration of pancreatic islet epigenomic and transcriptomic data produced by different labs worldwide. The Islet Regulome Browser is now accessible on the internet or may be installed locally. It allows uploading custom tracks as well as providing interactive access to a wealth of information including Genome-Wide Association Studies (GWAS) variants, different classes of regulatory elements, together with enhancer clusters, stretch-enhancers and transcription factor binding sites in pancreatic progenitors and adult human pancreatic islets. Integration and visualization of such data may allow a deeper understanding of the regulatory networks driving tissue-specific transcription and guide the identification of regulatory variants. We believe that such tool will facilitate the access to pancreatic islet public genomic datasets providing a major boost to functional genomics studies in glucose metabolism related traits including diabetes

Deep HST-WFPC2 photometry of NGC 288. II. The Main Sequence Luminosity Function

The Main Sequence Luminosity Function (LF) of the Galactic globular cluster NGC 288 has been obtained using deep WFPC2 photometry. We have employed a new method to correct for completeness and fully account for bin-to-bin migration due to blending and/or observational scatter. The effect of the presence of binary systems in the final LF is quantified and is found to be negligible. There is a strong indication of the mass segregation of unevolved single stars and clear signs of a depletion of low mass stars in NGC 288 with respect to other clusters. The results are in good agreement with the prediction of theoretical models of the dynamical evolution of NGC 288 that take into account the extreme orbital properties of this cluster.Comment: 16 pages, 6 .ps figures. Low resolution version of fig. 1; full resolution figure soon available at http://www.bo.astro.it/bap/BAPhome.html l. Latex. emulateapj5.sty macro included. Accepted for publication by The Astronomical Journa

Profiling of the Predicted Circular RNAs in Ductal In Situ and Invasive Breast Cancer: A Pilot Study

The recent advantage obtained by next generation sequencing allows a depth investigation of a new "old" kind of noncoding transcript, the circular RNAs. Circular RNAs are nontranslated RNAs, typically nonpolyadenylated, with a resistance to exonucleases that gives them the ability to be more stable than the common linear RNA isoforms. We used a bioinformatic detection tool (CIRCexplorer) to research predictive circRNAs from the next generation sequenced data of five samples of ductal in situ carcinoma (DCIS) and matched adjacent invasive ductal carcinoma (IDC). Furthermore, we also investigated the circular RNAs expressed in MCF7, an invasive breast ductal carcinoma cell line. We described the genomic context of the predicted circular RNAs and we address the hypothetical possible functional roles. This study showed a perspective of a panel of predictive circRNAs identified and the function that circRNAs could exert

Climate change may cause the extinction of the butterfly Lasiommata petropolitana in the Apennines

Climate change represents a threat to narrow-ranged mountain species living in low-altitude massifs. We studied the disjunct Apennine population of Lasiommata petropolitana (Lepidoptera, Nymphalidae) in the Gran Sasso and Monti della Laga National Park. We quantified the altitudinal shifts undergone in the last decades (1964–2021) in the Alps and Apennines and estimated the local extinction risk due to climate change. We also sequenced the COI mitochondrial marker of seven Apennine specimens, comparing them with those available across the Palearctic. We projected the probability of presence for the species under a future climatic scenario using an ensemble forecasting approach. We found that, despite geographical isolation, the Apennine population of L. petropolitana displays a single widespread COI haplotype also occurring in most European populations. In the Alps and Apennines, this species has shifted uphill an average of 6.3 m per year since 1964. Accordingly, our model predicted a likely extinction in the Apennines by about 2060, due to a reduction of the climatic suitability in this region. Implications for insect conservation Implications for insect conservation Despite its potential loss in the Apennines would not erode mitochondrial diversity, L. petropolitana characterises the butterfly community of the Gran Sasso massif as an alpine enclave. The loss of the Apennine population, together with those of other orophilous butterflies, could trigger a homogenization of alpha and beta diversity and induce a loss of functional diversity in the impoverished high-altitude biotas. As habitat heterogeneity is a key aspect for populations to endure climate change, the maintenance of varied microhabitats, mainly through grazing management, could address the decline of this population.Open access funding provided by Università degli Studi di Firenze within the CRUI-CARE Agreement. This study was funded by the Ministero Italiano della Transizione Ecologica within the project “Ricerca e conservazione sui lepidotteri diurni di sei Parchi Nazionali dell’Appennino Centro-Settentrionale”. Support was also provided by the Academy of Finland (Academy Research Fellow, decision no. 328895) to VD. RV is supported by Grant PID2019-107078 GB-I00 funded by Ministerio de Ciencia e Innovación and Agencia Estatal de Investigació

Remember me - user-centered implementation of working memory architectures on an industrial robot

The present research is innovative as we followed a user-centered approach to implement and train two working memory architectures on an industrial RB-KAIROS + robot: GRU, a state-of-the-art architecture, and WorkMATe, a biologically-inspired alternative. Although user-centered approaches are essential to create a comfortable and safe HRI, they are still rare in industrial settings. Closing this research gap, we conducted two online user studies with large heterogeneous samples. The major aim of these studies was to evaluate the RB-KAIROS + robot’s appearance, movements, and perceived memory functions before (User Study 1) and after the implementation and training of robot working memory (User Study 2). In User Study 1, we furthermore explored participants’ ideas about robot memory and what aspects of the robot’s movements participants found positive and what aspects they would change. The effects of participants’ demographic background and attitudes were controlled for. In User Study 1, participants’ overall evaluations of the robot were moderate. Participant age and negative attitudes toward robots led to more negative robot evaluations. According to exploratory analyses, these effects were driven by perceived low experience with robots. Participants expressed clear ideas of robot memory and precise suggestions for a safe, efficient, and comfortable robot navigation which are valuable for further research and development. In User Study 2, the implementation of WorkMATe and GRU led to more positive evaluations of perceived robot memory, but not of robot appearance and movements. Participants’ robot evaluations were driven by their positive views of robots. Our results demonstrate that considering potential users’ views can greatly contribute to an efficient and positively perceived robot navigation, while users’ experience with robots is crucial for a positive HRI

WALOWA (wave loads on walls) : large-scale experiments in the delta flume

Overtopping wave loads on vertical structures on top of a dike have been investigated in several small scale experiments in the past. A large-scale validation for a mild foreshore situation is still missing. Hence the WALOWA experimental campaign was carried out to address this topic. In the present paper the objectives of the WALOWA project are outlined in detail, the model and measurement set-up described and the test program presented. Furthermore, preliminary results featuring a single 1000 irregular waves test of the test program are highlighted. This includes the study of the mild and sandy foreshore evolution by comparing profiles before and after the test execution. The profile measurements are obtained with a mechanical profiler. The wave parameters offshore and at the dike toe are numerically simulated using a SWASH model. The numerical results are validated against the measurements. Finally, the force and pressure time series of the waves impacting against the wall are processed and filtered. The load cell measurements and the time series of integrated pressures are compared to each other and for each impact event the maximum force is derived.Hydraulic Structures and Flood RiskEnvironmental Fluid Mechanic

Linear electronics for Si-detectors and its energy calibration for use in heavy ion experiments

Abstract The design and implementation of linear electronics based on small-size, low-power charge preamplifiers and shaping amplifiers, used in connection with Si-detector telescopes employed in heavy ion experiments, are presented. Bench tests and "under beam" performances are discussed. In particular, the energy calibration and the linearity test of the overall system (Si-detector and linear and digital conversion electronics) has been performed with a procedure which avoids the pulse height defect problems connected with the detection of heavy ions. The procedure, basically, consists of using bursts of MeV protons, releasing up to GeV energies inside the detector, with low ionization density