Polymorphic micro-RNA targets and risk of colorectal cancer

Recent evidence indicate that small non-coding RNA molecules, called micro-RNAs (miRNA), can bind to the 3’UTRs of mRNAs and interfere with their translation, thereby regulating cell growth, differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms can reside on miRNA binding sites. Thus, it is conceivable that the miRNA regulation may be affected by polymorphisms on the 3’ UTRs. Since gene de-regulation is one of the key mechanisms by which cells can progress to cancer, we hypothesize that common polymorphisms within miRNA target binding sites could play a role in the individual risk of cancer. In the present study, we selected the 3’UTR regions of 129 genes candidate for colorectal cancer (CRC) and we identified putative miRNA binding sites by specialized algorithms (PicTar, DianaMicroT, miRBase, miRanda, TargetScan, and microInspector). We evaluated the SNPs for their ability to affect the binding of the miRNA with its target, by assessing the variation of Gibbs free energy between the two alleles of each SNP. We found 15 common polymorphisms. We added to this list 8 SNPs in miRNA sequences. All the polymorphisms were further investigated by a case-control association studies. The study was carried out on a series of cases and controls from Czech Republic, a population with the highest worldwide incidence of CRC. We found statistically significant associations between risk of CRC and variant alleles of CD86 (OR=2.74 95%CI=1.24-6.04, for the variant homozygotes) and INSR genes (OR=1.94; 95%CI=1.03-3.66, for the variant homozygotes). Then, these two polymorphisms were genotyped in three different populations: Spanish, Italian, and German.The statistical analyses for all the samples (Czech, Spanish, Italian, and German) confirmed the assciation between risk of CRC and the polymorphisms in CD86 and INSR. These results are the first reporting positive association between miRNA-binding SNPs sequences and cancer risk

Suscettibilità genetica al cancro al polmone: analisi di polimorfismi in geni deputati alla riparazione del DNA

RIASSUNTO Il cancro al polmone è il più comune carcinoma tra gli uomini nel mondo e la sua frequenza sta aumentando tra le donne. L’esposizione ad agenti cancerogeni endogeni ed ambientali è una delle più importanti cause di questo tipo di cancro negli esseri umani. All’interno degli agenti cancerogeni ambientali, il fumo di sigaretta è responsabile della maggior parte di casi di tumore al polmone e il rischio associato dipende dal numero di sigarette fumate. Tuttavia è stato stimato che solo il 15% circa di fumatori svilupperà un cancro al polmone dopo i 75 anni. Una possibile spiegazione è che geni implicati nel metabolismo del tabacco possono essere responsabili di una maggiore o minore suscettibilità a questo tumore in persone soggette ad un livello di esposizioni comparabili. Inoltre poiché cellule potenzialmente tumorali vengono riparate o indotte a suicidarsi (apoptosi ), l’efficienza dei geni deputati alla riparazione del DNA e dei geni soppressori tumorali deve esser considerata come un importante fattore nel determinare il rischio di cancro tra individui diversi. E’ importante riuscire a comprendere il ruolo di geni coinvolti in vari processi cellulari nel modulare la suscettibilità individuale a questo tumore. A questo fine abbiamo utilizzato 310 campioni di DNA di soggetti affetti da cancro al polmone e relativi controlli (soggetti sani rappresentativi di una popolazione generale, debitamente scelti con età simili al gruppo dei casi). I campioni sono stati selezionati da una coorte di 5000 persone in sei Paesi diversi: Polonia, Russia, Slovacchia, Romania, Ungheria e Repubblica Ceca. Attraverso l’analisi con un microarray sono stati genotipizzati 119 polimorfismi in 59 geni della riparazione del DNA e del ciclo cellulare. Stabilito il genotipo di ogni soggetto abbiamo eseguito un’analisi statistica dei dati mediante regressione logistica per identificare quali varianti alleliche investigate sono associate con la malattia. Abbiamo così trovato associazione significativa per i geni: ATM, LIG1, MSH6, MLH1, NOD2/ CARD15, XRCC4 e MTHFR. Dai nostri dati risulta che alcuni polimorfismi nei geni ATM, MLH1 e NOD2/ CARD15 sono associati con un diminuito rischio di cancro al polmone, mentre polimorfismi nei geni LIG1, MSH6, XRCC4 e MTHFR sono associati con un aumento del rischio della neoplasia

Oxidative Stress as a predictor of cardiovascular events in coronari artery disease patients

Abstract Background: Enhanced oxidative stress has been associated with atherosclerosis and coronary artery disease (CAD). However, the predictive value of circulating oxidative stress biomarkers for cardiovascular events (CE) in patients with CAD has remained poorly understood. Aim: To assess the prognostic significance of reactive oxygen metabolites, estimated as index of oxidative stress in serum samples by means of a commercial kit (ROMs, Diacron, Italy) on the rate of mortality and major adverse CE (MACE) in CAD. Methods: A study of 93 consecutive patients with angiographically documented CAD (75 males, age: 68?10 years, mean?SD) was made during a mean follow-up of 66 months until the occurrence of one of the following CE: cardiac and all cause death, non-fatal myocardial infarction and coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG)]. Patient data were retrospectively collected from the Institute\u27s electronic databank that saves demographic, clinical, instrumental and follow-up data of all patients admitted to our department. Results: The Kaplan-Meier survival estimates showed a significantly worst outcome in patients presenting elevated ROM level (>75th percentile, corresponding to 481 AU) (log rank=11, 7.5, 5.1; p<0.001, p<0.01, p<0.05 for cardiac and all cause death and MACEs, respectively). In a multivariate Cox regression model, elevated oxidative stress remained a significant predictor of cardiac and all cause death [hazard ratio (HR) 3.9, 95% confidence interval, 95% (CI) 1.4-11.1, p=0.01; HR=2.6, 95% CI 1.1-6.2, p=0.02) and MACE (HR=1.8, 95% CI 1.1-3.1, p=0.03)]. Conclusions: The estimation of ROMs may represent an additional prognostic tool in the assessment of CE in CAD patients

Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA,partial cds and 3\u27 UTR.

LOCUS HQ419060 318 bp mRNA linear PRI 24-NOV-2010 DEFINITION Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA, partial cds and 3\u27 UTR. ACCESSION HQ419060 VERSION HQ419060.1 GI:312261407 KEYWORDS . SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 318) AUTHORS Landi,S., Melaiu,O., Cabiati,M., Landi,D., Caselli,C., Prescimone,T., Giannessi,D., Gemignani,F. and Del Ry,S. TITLE Direct Submission JOURNAL Submitted (20-OCT-2010) Laboratory of Cardiovascular Biochemistry, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, PI 56100, Italy FEATURES Location/Qualifiers source 1..318 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /cell_line="SKNBE" /PCR_primers="fwd_seq: gtcagaagaagggcgacaag, rev_seq: gcgtttaaacgcgcacgcgt" gene <1..318 /gene="NPPC" CDS <1..188 /gene="NPPC" /codon_start=3 /product="natriuretic peptide precursor type C" /protein_id="ADQ54381.1" /db_xref="GI:312261408" /translation="GDRSRLLRDLRVDTKSRAAWARLLQEHPNARKYKGANKKGLSKG CFGLKLDRIGSMSGLGC" 3\u27UTR 189..318 /gene="NPPC" ORIGIN 1 agggcgaccg gtcgcgactg ctccgggacc tgcgcgtgga caccaagtcg cgggcagcgt 61 gggctcgcct tctgcaagag caccccaacg cgcgcaaata caaaggagcc aacaagaagg 121 gcttgtccaa gggctgcttc ggcctcaagc tggaccgaat cggctccatg agcggcctgg 181 gatgttagtg cggcgccccc tggcggcggg agaagaatga ttctgacact tggggaccag 241 ccttcagtag ctacccttgg aatgcctttg ctctcttctc tcctgtctaa acaacaaaga 301 gacggagtct gaggcct

The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes

MicroRNAs (miRNAs) are involved in post-transcriptional regulation of gene expression through binding to messenger RNAs (mRNA) thereby promoting mRNA degradation or altered translation. A single-nucleotide polymorphism (SNP) located within a miRNA-binding site could thus alter mRNA translation and influence cancer risk and treatment response. The common SNPs located within the 3′-untranslated regions of 20 DNA repair genes were analysed for putative miRNA-binding sites using bioinformatics algorithms, calculating the difference in Gibbs free binding energy (ΔΔG) for each wild-type versus variant allele. Seven SNPs were selected to be genotyped in germ line DNAs both from a bladder cancer case–control series (752 cases and 704 controls) and 202 muscle-invasive bladder cancer radiotherapy cases. The PARP-1 SNP rs8679 was also genotyped in a breast cancer case–control series (257 cases and 512 controls). Without adjustment for multiple testing, multivariate analysis demonstrated an association with increased bladder cancer risk with PARP1 rs8679 (Ptrend = 0.05) while variant homozygotes of PARP1 rs8679 were also noted to have an increased breast cancer risk (P = 0.03). In the radiotherapy cases, carriers of the RAD51 rs7180135 minor allele had improved cancer-specific survival (hazard ratio 0.52, 95% confidence interval 0.31–0.87, P = 0.01). This is the first report of associations between DNA repair gene miRNA-binding site SNPs with bladder and breast cancer risk and radiotherapy outcomes. If validated, these findings may give further insight into the biology of bladder carcinogenesis, allow testing of the RAD51 SNP as a potential predictive biomarker and also reveal potential targets for new cancer treatments

Scrittura e riscrittura nella narrativa di Oreste del Buono

La presente tesi di Laurea Specialistica in Lingua e Letteratura Italiana presenta l’analisi della produzione narrativa di Oreste del Buono, che costituisce l’aspetto meno conosciuto di questa vivace personalità culturale del novecento, piuttosto nota per la sua attività di giornalista e traduttore oppure per la direzione della rivista di fumetti «Linus». Il lavoro propone un dettagliato profilo biografico dello scrittore, del quale i dizionari biografici e le enciclopedie degli scrittori italiani riportano generalmente esigue notizie, per poi concentrarsi sull’analisi dei suoi romanzi. Dunque si descrive la svolta che intercorre tra gli scritti giovanili, espressione della sofferta malinconia dell’autore, e quelli della maturità letteraria, dominati invece dalla sua distaccata ironia, e si riflette sull’aspetto macroscopico della produzione letteraria, ovvero sull’intento metanarrativo. Il procedimento di scrittura e riscrittura costituisce il tratto peculiare di tutti i suoi romanzi e si mostra, col passare del tempo e nelle diverse modalità con cui viene realizzato nelle varie opere, sempre più evidente ed ostentato. Infine, ci si concentra sul carattere demistificatorio del linguaggio, sul quale del Buono riflette costantemente, ovvero sulla difficoltà e impossibilità della letteratura di riprodurre la vita nella sua interezza e complessità, sconfinando così nella metafora del labirinto dell’esistenza. Tuttavia, ciascun romanzo ripropone sempre lo scavo psicologico del personaggio, che si rivela quale autoanalisi di sé stesso, ma anche un dialogo parallelo e continuo con la società in cui vive, mostrandosi partecipe alle problematiche del suo tempo e solidale con gli altri uomini

Word\u2026 Moving

The project, through reflection and didactic experiences, pointed out that the movement/gesture, combined with the traditional sense organs, can promote language goals. Acquisitions consolidated in science consider the gesture-moving part of the senses, it integrates and interacts with the senses usually play. Based on these assumptions and a scientific experiment carried out in the 90s which shows that cognitive development goes through the daily practice without neglecting the movement, we wanted to experience, through the educational project "Words in motion ....", in a primary school in the province of Naples, the link between movement and gesture-learning reading and writing. The classes involved were 2 primary school. This project wanted to test if a strategy of teaching / learning active and creative, which reinforces the motivational orientation, the child leads to the acquisition of the tongue base. The methodological approach has served the contribution of analysis and synthesis with a peculiarity due to the presence of playful exercises on a floor-motor auditory-verbal and verbalmotor. The analysis of the data showed clearly that the experimental group has acquired more easily with the required skills. The teaching experience has shown the value of the applied methodology highlights the important contribution of recreational motor for learning the techniques of reading and writing. Body, communication and environment and coexist with each other, enabling children to realize their potential through the pleasure of perceiving and satisfaction manifest

WORD…MOVING

The project, through reflection and didactic experiences, pointed out that the movement/gesture, combined with the traditional sense organs, can promote language goals. Acquisitions consolidated in science consider the gesture-moving part of the senses, it integrates and interacts with the senses usually play. Based on these assumptions and a scientific experiment carried out in the 90s which shows that cognitive development goes through the daily practice without neglecting the movement, we wanted to experience, through the educational project "Words in motion ....", in a primary school in the province of Naples, the link between movement and gesture-learning reading and writing. The classes involved were 2 primary school. This project wanted to test if a strategy of teaching / learning active and creative, which reinforces the motivational orientation, the child leads to the acquisition of the tongue base. The methodological approach has served the contribution of analysis and synthesis with a peculiarity due to the presence of playful exercises on a floor-motor auditory-verbal and verbalmotor. The analysis of the data showed clearly that the experimental group has acquired more easily with the required skills. The teaching experience has shown the value of the applied methodology highlights the important contribution of recreational motor for learning the techniques of reading and writing. Body, communication and environment and coexist with each other, enabling children to realize their potential through the pleasure of perceiving and satisfaction manifest

LEARNING MATHEMATICS THROUGH THE BODY

The present study aimed to address the educational and teaching aspects related to the development of logical and mathematical thinking of the child. Going beyond the mind-body dualism, neuroscience has shown that mind and body are indivisibly united and shape all aspects of knowledge through a dialectical relationship with the external environment. The child gets to know the world thanks to its sensorimotor experiences that allow them to build the concepts, increasing the capability to discriminate, classify, process and contribute to the construction of logical-mathematical thinking. In addition to these scientific assumptions, this study was based on a survey carried out by the Third International Mathematics Science Study conducted in 1998, which showed the difficulty that children encounter in different types of schools when dealing with mathematical reasoning. The aim of this study was to test if a teaching / learning strategy based on active and constructive action that encourages exploration and research, would promote the comparison, discussion, creativity and reflective thinking of the child. The resource pack "Learning Mathematics through the Body" was used as a guide to plan the 14 units taught in the fourmonth period of this study which was conducted in a primary school in the province of Naples. The methodology included a first recreational sensorimotor phase in which the child becomes aware of the proposed objective, followed by a second phase characterized by the representation of the experience on an abstract level. The final phase included a structured test to assess the knowledge and skills acquired and provide the data to compare the control and experimental groups. The analysis of the data clearly evidenced that the experimental group acquired and assimilated more knowledge and skills. This highlighted the value of the methodology applied and can be concluded that body, mind and the environment, coexisting with each other, allow the child to assimilate mathematical symbolism more easily when applying it to real life situations