Functional characterization of the human PRUNE protein: implications in cancer.

The functional characterization of H-PRUNE was performed using different approaches, in order to elucidate first the biochemical function of the protein, and then the correlation with other genes and the role in different tumour types. First, we identified and characterized H-PRUNE phosphodiesterase activity, which is suppressed by dipyridamole. Interestingly, H-PRUNE interacts with NM23-Hl, an anti-metastatic protein involved in different processes as proliferation, differentiation and motility, suggesting us to investigate H-PRUNE possible correlation to tumour development and progression with respect to NM23-H1. Our study has consisted in elucidating H-PRUNE function in three different tumour types, as sarcoma, neuroblastoma, and breast cancer. Both sarcoma and breast cancer analyses revealed that H-PRUNE, localized into the cytoplasm, acts as a negative regulator of NM23-H1. In fact, both aggressive sarcoma subtypes and metastatic breast cancer showed high protein levels of H-PRUNE and low levels of NM23-H1, indicating its involvement in advanced stages of cancer. Moreover, we demonstrated that both the H-PRUNE phosphodiesterase activity and the H-PRUNE and NM23-H1 complex increase cell motility in the MDA-MB-435 breast cancer cell line. The overview of genes and pathways influenced by H-PRUNE overexpression in the MDA-MB-435 breast cancer cellular model has been performed in order to understand the molecular changes in tumour cells. Interestingly, we found high levels of H-PRUNE, localized into the nuclear compartment, correlated to high levels of both NM23-H1 and NM23-H2 (an isoform of the NM23 family) in advanced stages of neuroblastoma. We identified a new function of H-PRUNE as a transcriptional regulator of NM23-H2 and we postulated a transcriptional mechanism of regulation, including activation of NM23-H1 by NM23-H2 and of NM23-H2 by H-PRUNE. This study evidences H-PRUNE function, as a regulator of NM23-H1 anti-metastatic function by two different mechanisms of action, correlated to the different compartmentalization of H-PRUNE protein

Magnetic resonance imaging 3t and total fibrotic volume in autosomal dominant polycystic kidney disease

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. The aim of this study was to identify and quantify in ADPKD, through a novel MR protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the function renal. MATERIAL AND METHODS: 15 ADPKD patients undergone to renal MRI 3Tesla at T0 and revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima media thickness (IMT), ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS: Our study showed a significant negative correlation between total kidney volume and estimated glomerular filtration rate (eGFR) during observational observation (p<0.02). Moreover, we showed a negative correlation between eGFR with Total Fibrotic Volume (TFV) (p<0.04) and Total Perfusion Volume/Total kidney Volume(<0.02). Moreover TFV was correlated positively with PAC (p<0.05), insulin values (p<0.05), ABI (p <0.05) and LVMI(p<0.01). CONCLUSIONS: The MRI 3Tesla, despite the high costs, could be considered an useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger group are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies. This article is protected by copyright. All rights reserved

University as agent of change in terms of inclusion in working environments

Education can be considered an agent of change and one of the primary aims is to create feasible and inclusive pathways to strategically favour the realization of values and social change. The authors explore the role that universities can have in terms of agents of change for inclusion in the work environment, giving some methodological approaches. The results emerging from the literature analysis carried out during the IN-WORK (inclusive Communities at Work) project funded by the Erasmus + European Community will be presented

Efficacy of a Fixed Combination of Tetracycline, Chloramphenicol, and Colistimethate Sodium for Treatment of Candida albicans Keratitis

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“Sob a capa espessa da amnésia”: apagamentos visuais em Dora Bruder (1997), de Patrick Modiano

Este artigo objetiva buscar no romance Dora Bruder (1997), de Patrick Modiano, o significado e a relevância do apagamento visual como recurso narrativo, materializado na ausência das imagens fotográficas e no uso da écfrase para tratar do trauma deixado pela perseguição e morte de judeus durante a Segunda Guerra Mundial. A opção do autor por negar ao leitor a exposição da menina judia desaparecida em Paris durante a ocupação alemã é a metáfora da eliminação, do apagamento, do silenciamento e da morte da memória social de um povo. Em resposta a essa amnésia imposta, a memória é usada como meio de interrogar um passado que se transforma em narrativa para permitir a reelaboração de experiências dolorosas tornadas mais compreensíveis porque dizíveis

Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial

Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle

Understanding the Biological Significance of Anti-DFS70 Antibodies: Effect of Biologic Therapies on Their Occurrence in Inflammatory Arthritis

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Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation

Background: Many evidences report that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies. Results: We present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma. Conclusion: This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA

Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed