Mitochondrial caseinolytic protease p: A possible novel prognostic marker and therapeutic target in cancer

Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer

AUTOMATIC POINT CLOUD SEGMENTATION FOR THE DETECTION OF ALTERATIONS ON HISTORICAL BUILDINGS THROUGH AN UNSUPERVISED AND CLUSTERING-BASED MACHINE LEARNING APPROACH

Abstract. The article describes an innovative procedure for the three-dimensional analysis of decay morphologies of ancient buildings, through the application of machine learning methods for the automatic segmentation of point clouds. In the field of Cultural Heritage conservation, photogrammetric data can be exploited, for diagnostic and monitoring support, to recognize different typologies of alterations visible on the masonry surface, starting from colour information. Actually, certain stone and plaster surface pathologies (biological patina, biological colonization, chromatic alterations, spots,…) are typically characterized by chromatic variations. To this purpose, colour-based segmentation with hierarchical clustering has been implemented on colour data of point clouds, considered in the HSV colour-space. In addition, geometry-based segmentation of 3D reconstructions has been performed, in order to identify the main architectural elements (walls, vaults), and to associate them to the detected defects. The proposed workflow has been applied to some ancient buildings' environments, chosen because of their irregularity both in geometrical and colorimetric characteristics

ACCURACY EVALUATION OF SMARTPHONE-BASED VIDEOGRAMMETRY FOR CULTURAL HERITAGE DOCUMENTATION PROCESS

The last decade has seen the development of a growing tendency to use the most modern technologies, in the field of Cultural Heritage, with the aim of digitizing and facilitating protection and conservation activities. Much research has focused on the development of innovative methods such as photogrammetry or Terrestrial Laser Scanners, in terms of reliability, precision, time and costs. In this research, however, the use of the smartphone was investigated by comparing the point clouds obtained via videogrammetry from smartphones, with those generated by different digital survey techniques, such as Terrestrial Laser Scanners and photogrammetry via SLR camera. Specifically, a smartphone was used and the comparison between point clouds was conducted based on four criteria: point clouds fitting, density evaluation, profiling and texture quality with the aim, therefore, of verifying the geometric reliability of the data and the quality of polygonal lines and the mesh/texture derived. The case study selected was the sepulchral monument of the Pascopepe Lambertini family (14th century), located in the Crypt of Santa Maria della Scala, the Cathedral of Trani (South of Italy). Finally, the research demonstrates how this methodology, in the documentation of heritage, allows for even greater portability and accessibility compared to other methodologies, maintaining widely acceptable standards of accuracy and therefore going to constitute a valid alternative in the documentation of historical heritage

Candidate Genes and MiRNAs Linked to the Inverse Relationship Between Cancer and Alzheimer’s Disease: Insights From Data Mining and Enrichment Analysis

The incidence of cancer and Alzheimer\u2019s disease (AD) increases exponentially with age. A growing body of epidemiological evidence and molecular investigations inspired the hypothesis of an inverse relationship between these two pathologies. It has been proposed that the two diseases might utilize the same proteins and pathways that are, however, modulated differently and sometimes in opposite directions. Investigation of the common processes underlying these diseases may enhance the understanding of their pathogenesis and may also guide novel therapeutic strategies. Starting from a text-mining approach, our in silico study integrated the dispersed biological evidence by combining data mining, gene set enrichment, and protein-protein interaction (PPI) analyses while searching for common biological hallmarks linked to AD and cancer. We retrieved 138 genes (ALZCAN gene set), computed a significant number of enriched gene ontology clusters, and identified four PPI modules. The investigation confirmed the relevance of autophagy, ubiquitin proteasome system, and cell death as common biological hallmarks shared by cancer and AD. Then, from a closer investigation of the PPI modules and of the miRNAs enrichment data, several genes (SQSTM1, UCHL1, STUB1, BECN1, CDKN2A, TP53, EGFR, GSK3B, and HSPA9) and miRNAs (miR-146a-5p, MiR-34a-5p, miR-21-5p, miR-9-5p, and miR-16-5p) emerged as promising candidates. The integrative approach uncovered novel miRNA-gene networks (e.g., miR-146 and miR-34 regulating p62 and Beclin1 in autophagy) that might give new insights into the complex regulatory mechanisms of gene expression in AD and cancer

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Design: Cross-sectional, multicenter, clinical study. Participants: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. Measurements: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Results: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. Conclusions: The authors’ study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms

Prenatal tobacco smoke exposure increases hospitalizations for bronchiolitis in infants

BACKGROUND: Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women's and children's health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. METHODS: From November 2009 to December 2012, newborns born at ≥ 33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. RESULTS: Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4%) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5-8.1) and of 1.7 (CI 1.1-2.6) respectively. CONCLUSIONS: These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants' respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of lif