PTEN Gene: A Model for Genetic Diseases in Dermatology

PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it's likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN

Peripheral artery disease: potential role of ACE-inhibitor therapy

Subjects with peripheral arterial disease (PAD) of the lower limbs are at high risk for cardiovascular and cerebrovascular events and the prevalence of coronary artery disease in such patients is elevated. Recent studies have shown that regular use of cardiovascular medications, such as therapeutic and preventive agents for PAD patients, seems to be promising in reducing long-term mortality and morbidity. The angiotensin-converting-enzyme (ACE) system plays an important role in the pathogenesis and progression of atherosclerosis, and ACE-inhibitors (ACE-I) seem to have vasculoprotective and antiproliferative effects as well as a direct anti-atherogenic effect. ACE-I also promote the degradation of bradykinin and the release of nitric oxide, a potent vasodilator; further, thay have shown important implications for vascular oxidative stress. Other studies have suggested that ACE-I may also improve endothelial dysfunction. ACE-I are useful for reducing the risk of cardiovascular events in clinical and subclinical PAD. Particularly, one agent of the class (ie, ramipril) has shown in many studies to able to significantly reduce cardiovascular morbidity and mortality in patients with PAD

Non-responsive Dihydropteridine Reductase Deficiency

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Raman spectral shifts in naturally faulted rocks

Acknowledgements. We thank Colin Taylor at UoA for help in sample preparation.This study was supported by the School of Geosciences at the University of Aberdeen and in part by the NERC Centre for Doctoral Training in Oil & Gas (Grant Number: NE/R01051x/1).Peer reviewedPublisher PD

Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo

Nuclear factor TDP-43 has been reported to play multiple roles in transcription, pre-mRNA splicing, mRNA stability and mRNA transport. From a structural point of view, TDP-43 is a member of the hnRNP protein family whose structure includes two RRM domains flanked by the N-terminus and C-terminal regions. Like many members of this family, the C-terminal region can interact with cellular factors and thus serve to modulate its function. Previously, we have described that TDP-43 binds to several members of the hnRNP A/B family through this region. In this work, we set up a coupled minigene/siRNA cellular system that allows us to obtain in vivo data to address the functional significance of TDP-43-recruited hnRNP complex formation. Using this method, we have finely mapped the interaction between TDP-43 and the hnRNP A2 protein to the region comprised between amino acid residues 321 and 366. Our results provide novel details of protein–protein interactions in splicing regulation. In addition, we provide further insight on TDP-43 functional properties, particularly the lack of effects, as seen with our assays, of the disease-associated mutations that fall within the TDP-43 321-366 region: Q331K, M337V and G348C

An insight on the polyphase thermal history of the Internal Rif (Northern Morocco) through Raman micro-spectroscopy investigation

We are greatly indebted with M.N. Zaghloul for fruitful discussions and for introduce us to Rif geology. We kindly acknowledge the Editor in chief Federico Rossetti, the associated editor Giulio Viola and two anonymous reviewers for their constructive criticisms that improved the original version of this paper.Peer reviewedPostprin

Calibrating Carbonization Temperatures of Wood Fragments Embedded within Pyroclastic Density Currents through Raman Spectroscopy

The Grant of Excellence Departments, MIUR (ARTICOLO 1, COMMI 314–337 LEGGE 232/2016) is gratefully acknowledged. MathWorks is acknowledged for providing the Matlab license for this work. A version of the script for calculating temperatures from Raman spectra can be provided by the authors upon request. This research was funded by an MIUR Roma Tre post-doctoral grant (2017–20) No. REP. 22-PROT. 219 of 26 January 2017.Peer reviewedPublisher PD

LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms

Poly (ADP-ribose) polymerase 1 expression in fibroblasts of Down syndrome subjects

Abstract Down syndrome (DS) is the most common chromosomal disorder. It is featured by intellectual disability and is caused by trisomy 21. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Poly (ADP-ribose) polymerase 1 is a mediator of programmed-necrotic cell death and appears to be also involved in the apoptosis. The aim of the present work was to detect the intracellular distribution of PARP-1 protein using immunofluorescence techniques and the expression of PARP-1 mRNA in culture of fibroblasts of DS subjects. The analysis of the intracellular distribution of PARP-1 show a signal at the nuclear level in about 75 % of the cells of DS subjects with a slight uniformly fluorescent cytoplasm. In contrast, in about 65% of the analyzed fibroblasts of the normal subjects only a slight fluorescent was found. These observations have been confirmed by PARP-1 gene mRNA expression evaluation. The data obtained from this study strengthen the hypothesis that the over-expression of PARP-1 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS

Force measurements on storm walls due to overtopping waves: a middle-scale model experiment

The so-called post-overtopping processes are of wide interest for coastal engineers. Dedicated middle-scale tests have been carried out to measure impacts of an overtopped wave on a storm wall at low freeboard coastal structures. A smooth dike slope and a vertical wall, both with a promenade at crest level and a storm wall at the end of it, have been tested in a scale of 1/6. Impacts have been measured both with pressure and force transducers; the two systems provided similar results. A correlation between the hydraulic conditions and the wave impacts on the storm wall is proposed. Further analysis is ongoing to also include the post-overtopping characteristics to increase insight on the acting parameters in this proces