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131.
Alberto L'Abbate Gemma Macchia Pietro D'Addabbo Angelo Lonoce Doron Tolomeo Domenico Trombetta Klaas Kok Christoph Bartenhagen Christopher W. Whelan Orazio Palumbo Marco Severgnini Ingrid Cifola Martin Dugas Massimo Carella Gianluca De Bellis Mariano Rocchi Lucia Carbone Clelia Tiziana Storlazzi 《Nucleic acids research》2014,42(14):9131-9145
The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification. 相似文献
132.
Matthieu Legrand Benedetta De Berardinis Hanna K. Gaggin Laura Magrini Arianna Belcher Benedetta Zancla Alexandra Femia Mandy Simon Shweta Motiwala Rasika Sambhare Salvatore Di Somma Alexandre Mebazaa Vishal S. Vaidya James L. Januzzi Jr from the Global Research on Acute Conditions Team 《PloS one》2014,9(11)
Objective
The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).Methods
In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results
26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.Conclusions
In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). 相似文献133.
Valerio Mori Adolfo Amici Francesca Mazzola Michele Di Stefano Laura Conforti Giulio Magni Silverio Ruggieri Nadia Raffaelli Giuseppe Orsomando 《PloS one》2014,9(11)
NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the “amidated” and “deamidated” routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT), which in mammals comprises three distinct isozymes, and NAD synthetase (NADS). First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes''rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme''s substrate NaAD (nicotinic acid adenine dinucleotide). In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease. 相似文献
134.
135.
Pietro Cugini Loredana Di Palma Salvatore Di Simone Piernatale Lucia Paola Battisti Alessandro Coppola Giuseppe Leone 《Chronobiology international》1993,10(1):73-78
This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus. 相似文献
136.
Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)
Gustavo Jabor Gozzi Amanda do Rocio Andrade Pires Glaucio Valdameri Maria Eliane Merlin Rocha Glaucia Regina Martinez Guilhermina Rodrigues Noleto Alexandra Acco Carlos Eduardo Alves de Souza Aurea Echevarria Camilla Moretto dos Reis Attilio Di Pietro Sílvia Maria Suter Correia Cadena 《PloS one》2015,10(6)
In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. 相似文献
137.
138.
Ilya G. Kichigin Massimo Giovannotti Alex I. Makunin Bee L. Ng Marsel R. Kabilov Alexey E. Tupikin Vincenzo Caputo Barucchi Andrea Splendiani Paolo Ruggeri Willem Rens Patricia C. M. O’Brien Malcolm A. Ferguson-Smith Alexander S. Graphodatsky Vladimir A. Trifonov 《Molecular genetics and genomics : MGG》2016,291(5):1955-1966
139.
George Calin Guglielmina N Ranzani Dino Amadori Vlad Herlea Irina Matei Giuseppe Barbanti-Brodano Massimo Negrini 《BMC genetics》2001,2(1):14-7
Background
Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). 相似文献140.
Antonio Di Franco Agnese Marchini Pasquale Baiata Marco Milazzo Renato Chemello 《Biodiversity and Conservation》2009,18(5):1201-1217
Scuba diving is now one of the major form of commercial use of marine protected areas (MPAs) around the world and the control
of its potential impacts on the marine environment represents a fundamental key to manage this recreational activity in highly
dived areas. A potential tool to tackle such issues has been thought to be the definition of a value of recreational carrying
capacity of an area, but this approach has been rarely considered management-effective. Therefore, the first step for effectively
managing scuba-diving should be ‘bottom-up’: characterizing the benthic communities potentially affected by diving and evaluating
their vulnerability. Aim of this paper is to propose a tool to define an index of vulnerability for dive trails (STVI: scuba
trail vulnerability index). This has taken into consideration both physical and biological features of each trail. All the
considered features are represented by non-quantitative variables, because either they are purely qualitative or their quantitative
measurement is impractical. The management of such qualitative information and its translation into a formal methodology was
performed by means of fuzzy logic, which has been repeatedly proposed as a powerful technique to develop indices of environmental
quality. The approach adopted in this study provided a useful tool for the preliminary assessment of the potential vulnerability
of benthic assemblages to scuba-diving and may represent an alternative method to the assessment of carrying capacity. The
application of this index will enable management strategies for potentially reducing the degradation of benthic organisms/assemblages,
and allowing a sustainable use of MPAs. 相似文献