Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale

DEFF Research Database (Denmark)

Liu, Siyang; Huang, Shujia; Rao, Junhua

2015-01-01

present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome......) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We...... assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction...

Indirect evidence for a role of a subpopulation of activated neutrophils in the remodelling process after percutaneous coronary intervention

NARCIS (Netherlands)

Costa, MA; de Wit, LEA; de Valk, V.; Serrano, P; Wardeh, AJ; Serruys, PW; Sluiter, W

Aim Leukocytes have been implicated in restenosis following percutaneous transluminal coronary angioplasty. We investigated the link between the activated status of circulating neutrophils and restenosis after angioplasty. Methods and Results The population of 108 patients with single, de novo

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

Directory of Open Access Journals (Sweden)

Wehrenberg Scott

2010-01-01

Full Text Available Abstract Background Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials. Methods/Design The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1, single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to Discussion The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.

de novo'' aneurysms following endovascular procedures

International Nuclear Information System (INIS)

Briganti, F.; Cirillo, S.; Caranci, F.; Esposito, F.; Maiuri, F.

2002-01-01

Two personal cases of ''de novo'' aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of ''de novo'' aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the ''de novo'' aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous ''de novo'' aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of ''de novo'' aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a ''de novo'' aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for ''de novo'' aneurysm formation. (orig.)

MRUniNovo: an efficient tool for de novo peptide sequencing utilizing the hadoop distributed computing framework.

Science.gov (United States)

Li, Chuang; Chen, Tao; He, Qiang; Zhu, Yunping; Li, Kenli

2017-03-15

Tandem mass spectrometry-based de novo peptide sequencing is a complex and time-consuming process. The current algorithms for de novo peptide sequencing cannot rapidly and thoroughly process large mass spectrometry datasets. In this paper, we propose MRUniNovo, a novel tool for parallel de novo peptide sequencing. MRUniNovo parallelizes UniNovo based on the Hadoop compute platform. Our experimental results demonstrate that MRUniNovo significantly reduces the computation time of de novo peptide sequencing without sacrificing the correctness and accuracy of the results, and thus can process very large datasets that UniNovo cannot. MRUniNovo is an open source software tool implemented in java. The source code and the parameter settings are available at http://bioinfo.hupo.org.cn/MRUniNovo/index.php. s131020002@hnu.edu.cn ; taochen1019@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Detection of de novo single nucleotide variants in offspring of atomic-bomb survivors close to the hypocenter by whole-genome sequencing.

Science.gov (United States)

Horai, Makiko; Mishima, Hiroyuki; Hayashida, Chisa; Kinoshita, Akira; Nakane, Yoshibumi; Matsuo, Tatsuki; Tsuruda, Kazuto; Yanagihara, Katsunori; Sato, Shinya; Imanishi, Daisuke; Imaizumi, Yoshitaka; Hata, Tomoko; Miyazaki, Yasushi; Yoshiura, Koh-Ichiro

2018-03-01

Ionizing radiation released by the atomic bombs at Hiroshima and Nagasaki, Japan, in 1945 caused many long-term illnesses, including increased risks of malignancies such as leukemia and solid tumours. Radiation has demonstrated genetic effects in animal models, leading to concerns over the potential hereditary effects of atomic bomb-related radiation. However, no direct analyses of whole DNA have yet been reported. We therefore investigated de novo variants in offspring of atomic-bomb survivors by whole-genome sequencing (WGS). We collected peripheral blood from three trios, each comprising a father (atomic-bomb survivor with acute radiation symptoms), a non-exposed mother, and their child, none of whom had any past history of haematological disorders. One trio of non-exposed individuals was included as a control. DNA was extracted and the numbers of de novo single nucleotide variants in the children were counted by WGS with sequencing confirmation. Gross structural variants were also analysed. Written informed consent was obtained from all participants prior to the study. There were 62, 81, and 42 de novo single nucleotide variants in the children of atomic-bomb survivors, compared with 48 in the control trio. There were no gross structural variants in any trio. These findings are in accord with previously published results that also showed no significant genetic effects of atomic-bomb radiation on second-generation survivors.

Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis

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Bidesh Mahata

2014-05-01

Full Text Available T helper 2 (Th2 cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a “lymphosteroid,” a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.

De novo malignancy after pancreas transplantation in Japan.

Science.gov (United States)

Tomimaru, Y; Ito, T; Marubashi, S; Kawamoto, K; Tomokuni, A; Asaoka, T; Wada, H; Eguchi, H; Mori, M; Doki, Y; Nagano, H

2015-04-01

Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. We clarified the incidence of de novo malignancy after pancreas transplantation in Japan. Copyright © 2015 Elsevier Inc. All rights reserved.

Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease: the ABSORB cohort A trial.

Science.gov (United States)

Onuma, Yoshinobu; Dudek, Dariusz; Thuesen, Leif; Webster, Mark; Nieman, Koen; Garcia-Garcia, Hector M; Ormiston, John A; Serruys, Patrick W

2013-10-01

This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California). Multimodality imaging of the first-in-humans trial using a ABSORB BVS scaffold demonstrated at 2 years the bioresorption of the device while preventing restenosis. However, the long-term safety and efficacy of this therapy remain to be documented. In the ABSORB cohort A trial (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation), 30 patients with a single de novo coronary artery lesion were treated with the fully resorbable everolimus-eluting Absorb scaffold at 4 centers. As an optional investigation in 3 of the 4 centers, the patients underwent multislice computed tomography (MSCT) angiography at 18 months and 5 years. Acquired MSCT data were analyzed at an independent core laboratory (Cardialysis, Rotterdam, the Netherlands) for quantitative analysis of lumen dimensions and was further processed for calculation of fractional flow reserve (FFR) at another independent core laboratory (Heart Flow, Redwood City, California). Five-year clinical follow-up is available for 29 patients. One patient withdrew consent after 6 months, but the vital status of this patient remains available. At 46 days, 1 patient experienced a single episode of chest pain and underwent a target lesion revascularization with a slight troponin increase after the procedure. At 5 years, the ischemia-driven major adverse cardiac event rate of 3.4% remained unchanged. Clopidogrel was discontinued in all but 1 patient. Scaffold thrombosis was not observed in any patient. Two noncardiac deaths were reported, 1 caused by duodenal perforation and the other from Hodgkin's disease. At 5 years, 18 patients underwent MSCT angiography. All scaffolds were patent, with a median minimal lumen area of 3

Novel de novo BRCA2 mutation in a patient with a family history of breast cancer

DEFF Research Database (Denmark)

Hansen, Thomas V O; Bisgaard, Marie Luise; Jønson, Lars

2008-01-01

whole blood. The paternity was determined by single nucleotide polymorphism (SNP) microarray analysis. Parental origin of the de novo mutation was determined by establishing mutation-SNP haplotypes by variant specific PCR, while de novo and mosaic status was investigated by sequencing of DNA from......BACKGROUND: BRCA2 germ-line mutations predispose to breast and ovarian cancer. Mutations are widespread and unclassified splice variants are frequently encountered. We describe the parental origin and functional characterization of a novel de novo BRCA2 splice site mutation found in a patient...... and synthesis of a truncated BRCA2 protein. The aberrant splicing was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. The mutation was not found in any of the patient's parents or in the mother's carcinoma, showing it is a de novo mutation. Variant specific PCR indicates...

De novo origin of human protein-coding genes.

Directory of Open Access Journals (Sweden)

Dong-Dong Wu

2011-11-01

Full Text Available The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

De Novo Origin of Human Protein-Coding Genes

Science.gov (United States)

Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

2011-01-01

The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

Genes from scratch--the evolutionary fate of de novo genes.

Science.gov (United States)

Schlötterer, Christian

2015-04-01

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

Directory of Open Access Journals (Sweden)

Richard J Allen

2017-03-01

Full Text Available Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate of the pathway as a whole.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

Science.gov (United States)

Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

Long-term follow-up of young patients undergone coronary stenting

International Nuclear Information System (INIS)

Zhang Qi; Shen Weifeng; Zhang Jiansheng; Zhang Ruiyan; Hu Jian; Zhang Xian

2004-01-01

Objective: To evaluate the long-term effect of coronary stenting in young coronary artery diseased patients ( 45) undergoing coronary stenting were chosen randomly as the control group. Comparison the general characteristics, coronary angiographies, interventional and follow-up information between the two groups was undertaken. Results: Comparing with the control group, the young group patients presented much more myocardial infarctions (68% vs 35%, P<0.05) and single-vessel disease (83% vs 57%, P=0.001). Complete revascularization was achieved in 95% patients in the young group (95% vs control 78%, P=0.004). With a mean 67 ± 9 months follow-up, recurrent angina and readmission rate were higher in the young group, as well as the incidence of MACE. Repeat CAG revealed much more de novo lesions in the young group (44% vs 11%, P=0.02) and higher rate of re-stenting. Conclusions: Due to the high rate of complete circulatory reconstruction in young patients, the postprocedural events are probably caused by new coronary arterial lesions; therefore coronary stenting should be regarded as the primary choice of treatment. (authors)

Distilled single-cell genome sequencing and de novo assembly for sparse microbial communities.

Science.gov (United States)

Taghavi, Zeinab; Movahedi, Narjes S; Draghici, Sorin; Chitsaz, Hamidreza

2013-10-01

Identification of every single genome present in a microbial sample is an important and challenging task with crucial applications. It is challenging because there are typically millions of cells in a microbial sample, the vast majority of which elude cultivation. The most accurate method to date is exhaustive single-cell sequencing using multiple displacement amplification, which is simply intractable for a large number of cells. However, there is hope for breaking this barrier, as the number of different cell types with distinct genome sequences is usually much smaller than the number of cells. Here, we present a novel divide and conquer method to sequence and de novo assemble all distinct genomes present in a microbial sample with a sequencing cost and computational complexity proportional to the number of genome types, rather than the number of cells. The method is implemented in a tool called Squeezambler. We evaluated Squeezambler on simulated data. The proposed divide and conquer method successfully reduces the cost of sequencing in comparison with the naïve exhaustive approach. Squeezambler and datasets are available at http://compbio.cs.wayne.edu/software/squeezambler/.

Long-read sequencing and de novo assembly of a Chinese genome

Science.gov (United States)

Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arr...

Single coronary artery; extremely rare coronary anomaly successfully treated surgically in young adult male.

LENUS (Irish Health Repository)

Shah, A R

2010-05-01

Single coronary artery arising from aortic root, is a rare congenital anomaly. A 30-year-old male presented with acute myocardial infarction (MI) complaining of chest pain and raised troponin levels. Emergency angiography showed no coronary lesions but both left and right coronary arteries arising from single ostium. Patient was operated electively and perioperative findings confirmed the diagnosis of single coronary artery, as left coronary artery after taking origin from right sinus of valsalva runs through the septum, before dividing into left anterior descending and circumflex branches. The single coronary ostium opened with a slit like incision over the course of left main coronary, making the size of ostium three to four times bigger than the native one. In addition left internal mammary artery was harvested and grafted to the left anterior descending branch distally. Patient made successful recovery. Four months follow up dobutamine stress echo showed no inducible ischemia.

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

Science.gov (United States)

Dong, Shan; Walker, Michael F.; Carriero, Nicholas J.; DiCola, Michael; Willsey, A. Jeremy; Ye, Adam Y.; Waqar, Zainulabedin; Gonzalez, Luis E.; Overton, John D.; Frahm, Stephanie; Keaney, John F.; Teran, Nicole A.; Dea, Jeanselle; Mandell, Jeffrey D.; Bal, Vanessa Hus; Sullivan, Catherine A.; DiLullo, Nicholas M.; Khalil, Rehab O.; Gockley, Jake; Yuksel, Zafer; Sertel, Sinem M.; Ercan-Sencicek, A. Gulhan; Gupta, Abha R.; Mane, Shrikant M.; Sheldon, Michael; Brooks, Andrew I.; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.; Wei, Liping; Sanders, Stephan J.

2014-01-01

SUMMARY Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single nucleotide variants to autism spectrum disorders (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. Through the application of a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR=1.6; 95%CI=1.0-2.7; p=0.03), are more common in female probands (p=0.02), are enriched among genes encoding FMRP targets (p=6×10−9), and arise predominantly on the paternal chromosome (p<0.001). Based on mutation rates in probands versus unaffected siblings, de novo frameshift indels contribute to risk in approximately 3.0% of individuals with ASD. Finally, through observing clustering of mutations in unrelated probands, we report two novel ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. PMID:25284784

De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.

Science.gov (United States)

Eichenberger, Michael; Hansson, Anders; Fischer, David; Dürr, Lara; Naesby, Michael

2018-06-01

Anthocyanins (ACNs) are plant secondary metabolites responsible for most of the red, purple and blue colors of flowers, fruits and vegetables. They are increasingly used in the food and beverage industry as natural alternative to artificial colorants. Production of these compounds by fermentation of microorganisms would provide an attractive alternative. In this study, Saccharomyces cerevisiae was engineered for de novo production of the three basic anthocyanins, as well as the three main trans-flavan-3-ols. Enzymes from different plant sources were screened and efficient variants found for most steps of the biosynthetic pathway. However, the anthocyanidin synthase was identified as a major obstacle to efficient production. In yeast, this enzyme converts the majority of its natural substrates leucoanthocyanidins into the off-pathway flavonols. Nonetheless, de novo biosynthesis of ACNs was shown for the first time in yeast and for the first time in a single microorganism. It provides a framework for optimizing the activity of anthocyanidin synthase and represents an important step towards sustainable industrial production of these highly relevant molecules in yeast.

Genome-wide patterns and properties of de novo mutations in humans

NARCIS (Netherlands)

Francioli, Laurent C.; Polak, Paz P.; Koren, Amnon; Menelaou, Androniki; Chun, Sung; Renkens, Ivo; van Duijn, Cornelia M.; Swertz, Morris; Wijmenga, Cisca; van Ommen, Gertjan; Slagboom, P. Eline; Boomsma, Dorret I.; Ye, Kai; Guryev, Victor; Arndt, Peter F.; Kloosterman, Wigard P.; de Bakker, Paul I. W.; Sunyaev, Shamil R.

Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect(1-10). Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring

Genome-wide patterns and properties of de novo mutations in humans

NARCIS (Netherlands)

Francioli, L.C.; Polak, P.P.; Koren, A.; Menelaou, A.; Chun, S.; Renkens, I.; van Duijn, C.M.; Swertz, M.A.; Wijmenga, C.; van Ommen, G.J.; Slagboom, P.E.; Boomsma, D.I.; Ye, K.; Guryev, V.; Arndt, P.F.; Kloosterman, W.P.; Bakker, P.I.W.; Sunyaev, S.R.; Dijk, F.; Neerincx, P.B.T.; Pulit, S.L.; Deelen, P.; Elbers, C.C.; Palamara, P.F.; Pe'er, I.; Abdellaoui, A.; van Oven, M.; Vermaat, M.; Li, M.; Laros, J.F.J.; Stoneking, M.; de Knijff, P.; Kayser, M.; Veldink, J.H.; Van den Berg, L.H.; Byelas, H.; den Dunnen, J.T.; Dijkstra, M.; Amin, N.; van der Velde, K.J.; Hottenga, J.J.; van Setten, J.; van Leeuwen, E.M.; Kanterakis, A.; Kattenberg, V.M.; Karssen, L.C.; van Schaik, B.D.C.; Bot, J.; Nijman, I.J.; van Enckevort, D.; Mei, H.; Koval, V.; Estrada, K.; Medina-Gomez, C.; Lameijer, E.W.; Moed, M.H.; Hehir-Kwa, J.Y.; Handsaker, R.E.; McCarroll, S.A.; Vuzman, D.; Sohail, M.; Hormozdiari, F.; Marschall, T.; Schönhuth, A.; Beekman, M.; de Craen, A.J.; Suchiman, H.E.D.; Hofman, A.; Oostra, B.; Isaacs, A.; Rivadeneira, F.; Uitterlinden, A.G.; Willemsen, G.; Platteel, M.; Pitts, S.J.; Potluri, S.; Sundar, P.; Cox, D.R.; Li, Q.; Li, Y.; Du, Y.; Chen, R.; Cao, H.; Li, N.; Cao, S.; Wang, J.; Bovenberg, J.A.; Brandsma, M.

2015-01-01

Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of

Single Coronary Artery with Aortic Regurgitation

International Nuclear Information System (INIS)

Katsetos, Manny C.; Toce, Dale T.

2003-01-01

An isolated single coronary artery can be associated with normal life expectancy; however, patients are at an increased risk of sudden death. A case is reported of a 54-year-old man with several months of chest pressure with activity. On exercise Sestamibi stress testing, the patient developed a hypotensive response with no symptoms and minimal electrocardiographic changes. Nuclear scanning demonstrated reversible septal and lateral perfusion defects consistent with severe ischemia. Coronary angiography revealed a single coronary artery with the right coronary artery arising from the left main. There were high-grade stenotic lesions in the left anterior descending and circumflex arteries with only moderate atherosclerotic disease in the right coronary artery. An aortogram showed 2-3+ aortic regurgitation, with an ejection fraction of 45% on ventriculography. The patient underwent four-vessel revascularization and aortic valve replacement and did well postoperatively

The role of drug-eluting balloons alone or in combination with drug-eluting stents in the treatment of de novo diffuse coronary disease.

Science.gov (United States)

Costopoulos, Charis; Latib, Azeem; Naganuma, Toru; Sticchi, Alessandro; Figini, Filippo; Basavarajaiah, Sandeep; Carlino, Mauro; Chieffo, Alaide; Montorfano, Matteo; Naim, Charbel; Kawaguchi, Masanori; Giannini, Francesco; Colombo, Antonio

2013-11-01

This study sought to investigate the role of drug-eluting balloons (DEB) alone or in combination with drug-eluting stents (DES) in the treatment of diffuse de novo coronary artery disease (CAD) (>25 mm). The use of DEB in diffuse CAD, either alone or in combination with DES, offers an alternative to stenting alone. Data regarding DEB in this context are limited. We retrospectively evaluated all patients treated with DEB for diffuse CAD between June 2009 and October 2012. Endpoints analyzed were major adverse cardiac events, defined as all-cause death, myocardial infarction, and target vessel revascularization (TVR), as well as TVR and target lesion revascularization separately. Results were compared with those obtained from a cohort of patients with similar characteristics treated with DES alone. A total of 69 patients (93 lesions) were treated with DEB ± DES, and 93 patients with DES alone (93 lesions). A high proportion of patients were diabetic (46.4% vs. 44.1%, p = 0.77). Of the DEB-treated lesions, 56.0% were treated with DEB alone, 7.4% with DEB and DES as bail out, and 36.6% with DES and DEB as part of a hybrid approach for very long disease. Outcome rates with DEB ± DES were comparable to those with DES alone at 2-year follow-up (major adverse cardiac events = 20.8% vs. 22.7%, p = 0.74; TVR = 14.8% vs. 11.5%, p = 0.44; target lesion revascularization = 9.6% vs. 9.3%, p = 0.84). DEB may have a role in the treatment of diffuse de novo CAD, either alone in smaller vessels or in combination with DES in very long disease. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinicopathologic factors associated with de novo metastatic breast cancer.

Science.gov (United States)

Shen, Tiansheng; Siegal, Gene P; Wei, Shi

2016-12-01

While breast cancers with distant metastasis at presentation (de novo metastasis) harbor significantly inferior clinical outcomes, there have been limited studies analyzing the clinicopathologic characteristics in this subset of patients. In this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to identify factors associated with de novo metastatic breast cancer. When compared to patients without metastasis at presentation, race, histologic grade, estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly associated with de novo metastasis in the entire cohort, whereas age, histologic grade, PR and HER2 status were the significant parameters in the subset of patients with locally advanced breast cancer (Stage IIB/III). The patients with de novo metastatic breast cancer had a significant older mean age and a lower proportion of HER2-positive tumors when compared to those with metastatic recurrence. Further, the HER2-rich subtype demonstrated a drastically higher incidence of de novo metastasis when compared to the luminal and triple-negative breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively] and in the patients with locally advanced disease (OR=4.02 and 2.12, respectively), whereas no significant difference was seen between de novo metastatic cancers and those with metastatic recurrence. Moreover, the luminal and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99) characteristics, respectively, for the sites of de novo metastasis, while the latter was not observed in those with metastatic recurrence. Our data suggest that an algorithm incorporating clinicopathologic factors, especially histologic grade and receptor profile, remains of significant benefit during decision making in newly diagnosed breast cancer in the pursuit of precision medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

Comparison of in vivo acute stent recoil between the bioabsorbable everolimus-eluting coronary stent and the everolimus-eluting cobalt chromium coronary stent: insights from the ABSORB and SPIRIT trials

DEFF Research Database (Denmark)

Tanimoto, Shuzou; Serruys, Patrick W; Thuesen, Leif

2007-01-01

OBJECTIVES: This study sought to evaluate and compare in vivo acute stent recoil of a novel bioabsorbable stent and a metallic stent. BACKGROUND: The bioabsorbable everolimus-eluting coronary stent (BVS) is composed of a poly-L-lactic acid backbone, coated with a bioabsorbable polymer containing...... the antiproliferative drug, everolimus, and expected to be totally metabolized and absorbed in the human body. Because the BVS is made from polymer, it may have more acute recoil than metallic stents in vivo. METHODS: A total of 54 patients, who underwent elective stent implantation for single de novo native coronary...... artery lesions, were enrolled: 27 patients treated with the BVS and 27 patients treated with the everolimus-eluting cobalt chromium stent (EES). Acute absolute recoil, assessed by quantitative coronary angiography, was defined as the difference between mean diameter of the last inflated balloon...

Foldability of a Natural De Novo Evolved Protein.

Science.gov (United States)

Bungard, Dixie; Copple, Jacob S; Yan, Jing; Chhun, Jimmy J; Kumirov, Vlad K; Foy, Scott G; Masel, Joanna; Wysocki, Vicki H; Cordes, Matthew H J

2017-11-07

The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging diagnosis of congenital heart disease with single coronary artery

International Nuclear Information System (INIS)

Zhu Ming; Li Yuhua; Zhong Yumin; Sun Aimin

2003-01-01

Objective: To report 56 cases of congenital heart disease with congenital single coronary artery and to evaluate the imaging diagnostic techniques. Methods: All 56 patients with congenital single coronary artery underwent angiocardiography. Contrast enhancement magnetic resonance angiography (CE MRA) was performed in 4 cases. 48 cases were confirmed by operation. Results: In these 56 cases, single left coronary artery was found in 44 cases and single right coronary artery was found in 12. Conclusion: Congenital heart disease with congenital single coronary artery is not rare and correct diagnosis is very important for surgery

De novo assembly of highly diverse viral populations

Directory of Open Access Journals (Sweden)

Yang Xiao

2012-09-01

Full Text Available Abstract Background Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. Results We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software. Conclusions We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.

Propensity score matched lesion-based comparison of long-term clinical and angiographic outcomes after placement of sirolimus (Cypher Bx Velocity) and paclitaxel (TAXUS Express)-eluting stents for de novo native coronary stenosis.

Science.gov (United States)

Nakano, Yosuke; Ishikawa, Tetsuya; Hino, Shoryoku; Mutoh, Makoto

2014-04-01

Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were firstly compared in Japan. During PES-available period from May 2007 to February 2009, 1068 nonrandomized consecutive de novo native coronary lesions treated either with a PES (682 lesions) or SES were enrolled in this study, and a retrospective examination was conducted in April 2013. During that interval, the use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the baselines with a propensity score matching analysis produced 383 lesions in each arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after placement of SES (2.1 %; mean follow-up, 1400 ± 290 days) was not significantly different from that in the PES group (2.6 %; 1394 ± 325 days, p = 0.637). SES did not relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p = 0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in each arm), the incidence of binary restenosis (percent diameter stenosis [%DS] >50 %) in the SES group (12.0 %; mean follow-up, 477 ± 281 days) was not significantly different from that in the PES group (14.5 %; 497 ± 341 days, p = 0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40-1.32; p = 0.295). In conclusion, the present propensity score matched lesion-based analysis firstly showed the statistical equivalent long-term clinical and angiographic outcomes after either SES or PES placement for de novo native coronary lesion in Japanese patients in a daily practice environment.

''de novo'' aneurysms following endovascular procedures

Energy Technology Data Exchange (ETDEWEB)

Briganti, F.; Cirillo, S.; Caranci, F. [Department of Neurological Sciences, Services of Neuroradiology, ' ' Federico II' ' University, Naples (Italy); Esposito, F.; Maiuri, F. [Department of Neurological Sciences, Services of Neurosurgery, ' ' Federico II' ' University, Naples (Italy)

2002-07-01

Two personal cases of ''de novo'' aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of ''de novo'' aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the ''de novo'' aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous ''de novo'' aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of ''de novo'' aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a ''de novo'' aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for ''de novo'' aneurysm formation. (orig.)

On the Origin of De Novo Genes in Arabidopsis thaliana Populations.

Science.gov (United States)

Li, Zi-Wen; Chen, Xi; Wu, Qiong; Hagmann, Jörg; Han, Ting-Shen; Zou, Yu-Pan; Ge, Song; Guo, Ya-Long

2016-08-03

De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Incidence, feasibility and outcome of percutaneous coronary intervention after transcatheter aortic valve implantation with a self-expanding prosthesis. Results from a single center experience.

Science.gov (United States)

Allali, Abdelhakim; El-Mawardy, Mohamed; Schwarz, Bettina; Sato, Takao; Geist, Volker; Toelg, Ralph; Richardt, Gert; Abdel-Wahab, Mohamed

2016-09-01

Percutaneous coronary intervention (PCI) after transcatheter aortic valve implantation (TAVI) can become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which completely covers the aortic root. The aim of this study was to report on the incidence, feasibility and outcome of PCI after TAVI with the MCV device. Between 2007 and 2014, all patients subjected to PCI after MCV implantation in a single-center institutional TAVI database were retrospectively identified. Clinical, angiographic and procedural characteristics were reviewed and analyzed. We identified a total of 17 patients (5.7%) treated with 24 PCI procedures for 29 lesions at a median of 17.7months (range 1-72) after MCV implantation. The mean age was 79.7±6.8years and the mean logistic EuroSCORE was 30.3%±18.9%. Nine procedures were performed for patients with acute coronary syndrome. 89.6% of the treated lesions were of type B2/C and 79.3% were de novo ones. A median of one guiding catheter was necessary to intubate the target coronary ostium (range 1-10) and 95% of the lesions on the left coronary artery were treated through a Judkins catheter. In one primary PCI for STEMI the intubation of the right coronary ostium was not successful. Final procedural success was obtained in 95.8%, and peri-procedural death occurred in one patient. The need for PCI after MCV is not uncommon and is mostly related to coronary artery disease progression. PCI after MCV is usually feasible and safe, but coronary intubation in an emergency setting can be challenging. Copyright © 2016 Elsevier Inc. All rights reserved.

Glucagon infusion increases rate of purine synthesis de novo in rat liver

International Nuclear Information System (INIS)

Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

1987-01-01

Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

Extreme-Scale De Novo Genome Assembly

Energy Technology Data Exchange (ETDEWEB)

Georganas, Evangelos [Intel Corporation, Santa Clara, CA (United States); Hofmeyr, Steven [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Egan, Rob [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Buluc, Aydin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Rokhsar, Daniel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Yelick, Katherine [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.

2017-09-26

De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and the large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.

High frequencies of de novo CNVs in bipolar disorder and schizophrenia.

LENUS (Irish Health Repository)

Malhotra, Dheeraj

2011-12-22

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

De Novo Construction of Redox Active Proteins.

Science.gov (United States)

Moser, C C; Sheehan, M M; Ennist, N M; Kodali, G; Bialas, C; Englander, M T; Discher, B M; Dutton, P L

2016-01-01

Relatively simple principles can be used to plan and construct de novo proteins that bind redox cofactors and participate in a range of electron-transfer reactions analogous to those seen in natural oxidoreductase proteins. These designed redox proteins are called maquettes. Hydrophobic/hydrophilic binary patterning of heptad repeats of amino acids linked together in a single-chain self-assemble into 4-alpha-helix bundles. These bundles form a robust and adaptable frame for uncovering the default properties of protein embedded cofactors independent of the complexities introduced by generations of natural selection and allow us to better understand what factors can be exploited by man or nature to manipulate the physical chemical properties of these cofactors. Anchoring of redox cofactors such as hemes, light active tetrapyrroles, FeS clusters, and flavins by His and Cys residues allow cofactors to be placed at positions in which electron-tunneling rates between cofactors within or between proteins can be predicted in advance. The modularity of heptad repeat designs facilitates the construction of electron-transfer chains and novel combinations of redox cofactors and new redox cofactor assisted functions. Developing de novo designs that can support cofactor incorporation upon expression in a cell is needed to support a synthetic biology advance that integrates with natural bioenergetic pathways. © 2016 Elsevier Inc. All rights reserved.

De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

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Veronique Hamel

2017-01-01

Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder

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Shan Dong

2014-10-01

Full Text Available Summary: Whole-exome sequencing (WES studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs to autism spectrum disorder (ASD. However, challenges in the reliable detection of de novo insertions and deletions (indels have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals, we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0–2.7; p = 0.03, are more common in female probands (p = 0.02, are enriched among genes encoding FMRP targets (p = 6 × 10−9, and arise predominantly on the paternal chromosome (p < 0.001. On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. : Insertions and deletions (indels have proven especially difficult to detect in exome sequencing data. Dong et al. now identify indels in exome data for 787 autism spectrum disorder (ASD families. They demonstrate association between de novo indels that alter the reading frame and ASD. Furthermore, by observing clustering of indels in unrelated probands, they uncover two additional ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.

De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

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Kanodia K

2008-01-01

Full Text Available Collapsing glomerulopathy (CG, characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.

De novo giant A2 aneurysm following anterior communicating artery occlusion.

Science.gov (United States)

Ibrahim, Tarik F; Hafez, Ahmad; Andrade-Barazarte, Hugo; Raj, Rahul; Niemela, Mika; Lehto, Hanna; Numminen, Jussi; Jarvelainen, Juha; Hernesniemi, Juha

2015-01-01

De novo intracranial aneurysms are reported to occur with varying incidence after intracranial aneurysm treatment. They are purported to be observed, however, with increased incidence after Hunterian ligation; particularly in cases of carotid artery occlusion for giant or complex aneurysms deemed unclippable. We report a case of right-sided de novo giant A2 aneurysm 6 years after an anterior communicating artery (ACoA) aneurysm clipping. We believe this de novo aneurysm developed in part due to patient-specific risk factors but also a significant change in cerebral hemodynamics. The ACoA became occluded after surgery that likely altered the cerebral hemodynamics and contributed to the de novo aneurysm. We believe this to be the first reported case of a giant de novo aneurysm in this location. Following parent vessel occlusion (mostly of the carotid artery), there are no reports of any de novo aneurysms in the pericallosal arteries let alone a giant one. The patient had a dominant right A1 and the sudden increase in A2 blood flow likely resulted in increased wall shear stress, particularly in the medial wall of the A2 where the aneurysm occurred 2 mm distal to the A1-2 junction. ACoA preservation is a key element of aneurysm surgery in this location. Suspected occlusion of this vessel may warrant closer radiographic follow-up in patients with other risk factors for aneurysm development.

Purine biosynthesis de novo by lymphocytes in gout

International Nuclear Information System (INIS)

Kamoun, P.; Chanard, J.; Brami, M.; Funck-Brentano, J.L.

1978-01-01

A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [ 14 C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. Synthesis of 14 C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values contained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [ 14 C]glycine incorporation into urinary uric acid. (author)

de novo computational enzyme design.

Science.gov (United States)

Zanghellini, Alexandre

2014-10-01

Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional assessment of sequential coronary artery fistula and coronary artery stenosis with fractional flow reserve and stress adenosine myocardial perfusion imaging

Directory of Open Access Journals (Sweden)

Kuan Leong Yew

2015-10-01

Full Text Available Coronary artery fistula is an abnormal connection between one coronary artery to another coronary artery or cardiac chambers. The coronary artery fistula may cause significant shunting of blood and cause “pseudo-stenosis” or “steal phenomenon”. This will also accentuate pre-existing mild-moderate de novo coronary lesions with resultant greater pressure gradient difference across the lesions. Thus, fractional flow reserve can be a useful tool to guide intervention decision on the coronary artery fistula. There are very few published reports regarding the use of FFR to assess coronary artery fistula. In fact, there is no outcome data regarding the deferment of coronary artery fistula intervention when the FFR is not physiologically significant. This case highlighted the use of FFR to evaluate the functional significance of coronary fistula in the setting of ischemia evaluation and it was proven to be safe to defer intervention with good 3 year clinical outcome. Stress adenosine myocardial perfusion imaging correlated with the FFR result.

Response monitoring in de novo patients with Parkinson's disease.

Directory of Open Access Journals (Sweden)

Rita Willemssen

Full Text Available BACKGROUND: Parkinson's disease (PD is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD". METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

DEFF Research Database (Denmark)

2014-01-01

in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p...... = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have...... analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1...

Genome sequencing of bacteria: sequencing, de novo assembly and rapid analysis using open source tools.

Science.gov (United States)

Kisand, Veljo; Lettieri, Teresa

2013-04-01

De novo genome sequencing of previously uncharacterized microorganisms has the potential to open up new frontiers in microbial genomics by providing insight into both functional capabilities and biodiversity. Until recently, Roche 454 pyrosequencing was the NGS method of choice for de novo assembly because it generates hundreds of thousands of long reads (tools for processing NGS data are increasingly free and open source and are often adopted for both their high quality and role in promoting academic freedom. The error rate of pyrosequencing the Alcanivorax borkumensis genome was such that thousands of insertions and deletions were artificially introduced into the finished genome. Despite a high coverage (~30 fold), it did not allow the reference genome to be fully mapped. Reads from regions with errors had low quality, low coverage, or were missing. The main defect of the reference mapping was the introduction of artificial indels into contigs through lower than 100% consensus and distracting gene calling due to artificial stop codons. No assembler was able to perform de novo assembly comparable to reference mapping. Automated annotation tools performed similarly on reference mapped and de novo draft genomes, and annotated most CDSs in the de novo assembled draft genomes. Free and open source software (FOSS) tools for assembly and annotation of NGS data are being developed rapidly to provide accurate results with less computational effort. Usability is not high priority and these tools currently do not allow the data to be processed without manual intervention. Despite this, genome assemblers now readily assemble medium short reads into long contigs (>97-98% genome coverage). A notable gap in pyrosequencing technology is the quality of base pair calling and conflicting base pairs between single reads at the same nucleotide position. Regardless, using draft whole genomes that are not finished and remain fragmented into tens of contigs allows one to characterize

Defining the maize transcriptome de novo using deep RNA-Seq

Energy Technology Data Exchange (ETDEWEB)

Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

2011-06-01

De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

Defining the maize transcriptome de novo using deep RNA-Seq

Energy Technology Data Exchange (ETDEWEB)

Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

2011-06-02

De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly

DEFF Research Database (Denmark)

Li, Yingrui; Zheng, Hancheng; Luo, Ruibang

2011-01-01

Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise...

Demanda dos principais metais e novos materiais : analise de tendencias

OpenAIRE

Wilson Trigueiro de Sousa

1990-01-01

Resumo: Neste trabalho são analisadas algumas tendências na área de novos materiais na tentativa de obter um melhor entendimento das repercussões das atuais inovações tecnológicas para o setor mineral. Inicialmente são revisados os principais estudos sobre as mudanças ocorridas por volta de 1972/74 no comportamento da demanda dos metais mais importantes. Entre as possíveis causas, está o progresso técnico, que tornou possível o surgimento de novos materiais e o aperfeiçoamento de outros em us...

Avaliação prognóstica da doença coronária estável através de um novo escore Evaluación pronóstica de la enfermedad coronaria estable a través de un nuevo score New prognostic score for stable coronary disease evaluation

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Fernanda Coutinho Storti

2011-05-01

Full Text Available FUNDAMENTO: A necessidade de melhorar a acurácia do teste de esforço, determinou o desenvolvimento de escores, cuja aplicabilidade já foi amplamente reconhecida. OBJETIVO: Avaliação prognóstica do coronariopata estável através de um novo escore simplificado. MÉTODOS: Um novo escore foi aplicado em 372 coronariopatas multiarteriais e função ventricular preservada, 71,8% homens, idade média 59,5 (± 9,07 anos, randomizados para angioplastia, revascularização cirúrgica e tratamento clínico, acompanhados por 5 anos. Óbito cardiovascular foi o desfecho primário. Infarto do miocárdio não-fatal, óbito e re-intervenção formaram o desfecho combinado secundário. O escore baseou-se numa equação previamente validada resultante da soma de 1 ponto para: sexo masculino, história de infarto, angina, diabete, uso de insulina e ainda 1 ponto para cada década de vida a partir dos 40 anos. Teste positivo adicionou 1 ponto. RESULTADOS: Ocorreram 36 óbitos (10 no grupo angioplastia, 15 no grupo revascularização e 11 no grupo clínico, p = 0,61. Observou-se 93 eventos combinados: 37 no grupo angioplastia, 23 no grupo revascularização e 33 no grupo clínico (p = 0,058. 247 pacientes apresentaram escore clínico > 5 pontos e 216 > 6 pontos. O valor de corte > 5 ou > 6 pontos identificou maior risco, com p = 0,015 e p = 0,012, respectivamente. A curva de sobrevida mostrou uma incidência de óbito após a randomização diferente naqueles com escore > 6 pontos (p = 0,07, e uma incidência de eventos combinados diferente entre pacientes com escore 6 pontos (p = 0,02. CONCLUSÃO: O novo escore demonstrou consistência na avaliação prognóstica do coronariopata estável multiarterial.FUNDAMENTO: La necesidad de mejorar la exactitud de las pruebas de estrés, determinó el desarrollo de los puntajes, cuya aplicación fue ampliamente reconocida. OBJETIVO: La evaluación pronóstica del coronariópata estable a través de un nuevo score

Successful transcatheter closure of coronary artery fistula in a child with single coronary artery: a heavy load and a long road.

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Phasalkar, Manjunath; Thakkar, Bhavesh; Poptani, Vishal

2013-07-01

Single coronary artery is an uncommon variation of the coronary circulation. After transposition of great arteries, coronary artery fistulas are the most common associated cardiac anomalies in these patients. Transcatheter closure of coronary artery fistula (CAF) involving single coronary artery is a challenging intervention. In the absence of contralateral coronary artery, a complex anatomy of the CAF and a large myocardial perfusion territory of the dominant circulation pose an additional risk during interventional procedure. We report our experience of a successful transcatheter closure of a coronary artery fistula in a patient with single coronary artery. Copyright © 2013 Wiley Periodicals, Inc.

Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

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Chen, Yi-Chan; Cheng, Chih-Hsien; Wang, Yu-Chao; Wu, Ting-Jun; Chou, Hong-Shiue; Chan, Kun-Ming; Lee, Wei-Chen; Lee, Chen-Fang; Soong, Ruey Shyang

2016-09-01

Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population.From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports.Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population.Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

Optimizing de novo common wheat transcriptome assembly using short-read RNA-Seq data

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Duan Jialei

2012-08-01

Full Text Available Abstract Background Rapid advances in next-generation sequencing methods have provided new opportunities for transcriptome sequencing (RNA-Seq. The unprecedented sequencing depth provided by RNA-Seq makes it a powerful and cost-efficient method for transcriptome study, and it has been widely used in model organisms and non-model organisms to identify and quantify RNA. For non-model organisms lacking well-defined genomes, de novo assembly is typically required for downstream RNA-Seq analyses, including SNP discovery and identification of genes differentially expressed by phenotypes. Although RNA-Seq has been successfully used to sequence many non-model organisms, the results of de novo assembly from short reads can still be improved by using recent bioinformatic developments. Results In this study, we used 212.6 million pair-end reads, which accounted for 16.2 Gb, to assemble the hexaploid wheat transcriptome. Two state-of-the-art assemblers, Trinity and Trans-ABySS, which use the single and multiple k-mer methods, respectively, were used, and the whole de novo assembly process was divided into the following four steps: pre-assembly, merging different samples, removal of redundancy and scaffolding. We documented every detail of these steps and how these steps influenced assembly performance to gain insight into transcriptome assembly from short reads. After optimization, the assembled transcripts were comparable to Sanger-derived ESTs in terms of both continuity and accuracy. We also provided considerable new wheat transcript data to the community. Conclusions It is feasible to assemble the hexaploid wheat transcriptome from short reads. Special attention should be paid to dealing with multiple samples to balance the spectrum of expression levels and redundancy. To obtain an accurate overview of RNA profiling, removal of redundancy may be crucial in de novo assembly.

Autosomal dominant cutis laxa with progeroid features due to a novel, de novo mutation in ALDH18A1.

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Bhola, Priya T; Hartley, Taila; Bareke, Eric; Boycott, Kym M; Nikkel, Sarah M; Dyment, David A

2017-06-01

De novo dominant mutations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1) gene have recently been shown to cause autosomal dominant cutis laxa with progeroid features (MIM 616603). To date, all de novo dominant mutations have been found in a single highly conserved amino acid residue at position p.Arg138. We report an 8-year-old male with a clinical diagnosis of autosomal dominant cutis laxa (ADCL) with progeroid features and a novel de novo missense mutation in ALDH18A1 (NM_002860.3: c.377G>A (p.Arg126His)). This is the first report of an individual with ALDH18A1-ADCL due to a substitution at a residue other than p.Arg138. Knowledge of the complete spectrum of dominant-acting mutations that cause this rare syndrome will have implications for molecular diagnosis and genetic counselling of these families.

Recurrence risk in de novo structural chromosomal rearrangements.

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Röthlisberger, Benno; Kotzot, Dieter

2007-08-01

According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

Estudo do mecanismo de ação de novos compostos de ruténio com atividade antitumoral

OpenAIRE

Carvalho, Andreia Catarina Guerreiro Morais de

2017-01-01

Tese de mestrado, Bioquímica (Bioquímica Médica), Universidade de Lisboa, Faculdade de Ciências, 2017 A quimioterapia é um tratamento tradicional do cancro. Sua alta toxicidade, afetando tecidos saudáveis, e a resistência intrínseca a fármacos são obstáculos que precisam de ser superados. Desta forma, a identificação de novos agentes quimioterapêuticos é fundamental para novos progressos no tratamento do cancro. Uma abordagem inclui complexos de ruténio, que foram reconhecidos como uma alt...

Generative Recurrent Networks for De Novo Drug Design.

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Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

2018-01-01

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

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Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

2015-02-01

De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

Diagnostic performance of coronary CT angiography, stress dual-energy CT perfusion, and stress perfusion single-photon emission computed tomography for coronary artery disease: Comparison with combined invasive coronary angiography and stress perfusion cardiac MRI

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Chung, Hyun Woo; Ko, Sung Min; Hwang, Hweung Kon; So, Young; Yi, Jeong Geun [Konkuk University Medical Center, Research Institute of Biomedical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Eun Jeong [Dept. of Nuclear Medicine, Seoul Medical Center, Seoul (Korea, Republic of)

2017-06-15

To investigate the diagnostic performance of coronary computed tomography angiography (CCTA), stress dual-energy computed tomography perfusion (DE-CTP), stress perfusion single-photon emission computed tomography (SPECT), and the combinations of CCTA with myocardial perfusion imaging (CCTA + DE-CTP and CCTA + SPECT) for identifying coronary artery stenosis that causes myocardial hypoperfusion. Combined invasive coronary angiography (ICA) and stress perfusion cardiac magnetic resonance (SP-CMR) imaging are used as the reference standard. We retrospectively reviewed the records of 25 patients with suspected coronary artery disease, who underwent CCTA, DE-CTP, SPECT, SP-CMR, and ICA. The reference standard was defined as ≥ 50% stenosis by ICA, with a corresponding myocardial hypoperfusion on SP-CMR. For per-vascular territory analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 96, 96, 68, 93, and 68%, respectively, and specificities were 72, 75, 89, 85, and 94%, respectively. The areas under the receiver operating characteristic curve (AUCs) were 0.84 ± 0.05, 0.85 ± 0.05, 0.79 ± 0.06, 0.89 ± 0.04, and 0.81 ± 0.06, respectively. For per-patient analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 100, 100, 89, 100, and 83%, respectively; the specificities were 14, 43, 57, 43, and 57%, respectively; and the AUCs were 0.57 ± 0.13, 0.71 ± 0.11, 0.73 ± 0.11, 0.71 ± 0.11, and 0.70 ± 0.11, respectively. The combination of CCTA and DE-CTP enhances specificity without a loss of sensitivity for detecting hemodynamically significant coronary artery stenosis, as defined by combined ICA and SP-CMR.

Arginine de novo and nitric oxide production in disease states

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Luiking, Yvette C.; Ten Have, Gabriella A. M.; Wolfe, Robert R.; Deutz, Nicolaas E. P.

2012-01-01

Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin ...

De novo autoimmune hepatitis after liver transplantation.

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Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

2007-10-01

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

De novo pathway-based biomarker identification

DEFF Research Database (Denmark)

Alcaraz, Nicolas; List, Markus; Batra, Richa

2017-01-01

in a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) revealed that MGs are considerably more stable than SG models, while also providing valuable insight into the cancer hallmarks that drive them. In addition, when tested on an independent benchmark non-TCGA dataset, MG features......Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent...... on their molecular subtypes can provide a detailed view of the disease and lead to more personalized therapies. We propose and discuss a novel MG approach based on de novo pathways, which for the first time have been used as features in a multi-class setting to predict cancer subtypes. Comprehensive evaluation...

De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

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Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

2018-05-01

Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

Combined "de novo" and "ex novo" lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis.

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Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Qi, Gao-Xiang; Xiong, Lian; Lin, Xiao-Qing; Wang, Can; Li, Hai-Long; Chen, Xin-De

2017-01-01

Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways (" de novo " lipid fermentation and " ex novo " lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both " de novo " and " ex novo " lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined " de novo " and " ex novo " lipid fermentation by oleaginous yeast Trichosporon dermatis . Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis . Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis . The present study proves the potential and possibility of combined " de novo " and " ex novo " lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

High Incidence of De Novo and Subclinical Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy and Cardiac Rhythm Management Device.

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Wilke, Iris; Witzel, Katrin; Münch, Julia; Pecha, Simon; Blankenberg, Stephan; Reichenspurner, Hermann; Willems, Stephan; Patten, Monica; Aydin, Ali

2016-07-01

Atrial fibrillation (AF) is an important prognostic parameter in patients with hypertrophic cardiomyopathy (HCM). Though cardiac rhythm management (CRM) devices (e.g., ICD, pacemaker or implantable loop recorder) can detect subclinical AF, data describing the incidence of AF are rare. We therefore investigated the incidence and clinical impact of de novo and subclinical AF detected by CRM devices in patients with HCM. In our retrospective single-center study, we included patients with HCM and need for CRM devices. The primary endpoint of the study was the incidence of clinical and subclinical de novo AF. During follow-up, patients were screened for adverse events like stroke, ventricular arrhythmia, heart failure, or death. From 192 HCM patients, 44 patients received a CRM device (38 ICDs, 5 pacemakers, 1 implantable loop recorder). In 14 of these patients (32%), AF had been documented before device implantation. Thirty (68%) patients were free from AF at the time of implantation. During a median follow-up of 595 days (interquartile range, 367-890 days), de novo AF was recorded in 16 of these 30 patients (53%). Fourteen (88%) of the 16 patients with de novo AF were free from any clinical symptoms, so these patients were classified to have subclinical AF. In logistic regression analysis, age was the only significant predictor for an increased risk of AF. AF is common in patients with HCM who need a CRM device. More than 50% of these patients develop de novo AF that was predominantly subclinical in our cohort. © 2016 Wiley Periodicals, Inc.

Airline Maintenance Manpower Optimization from the De Novo Perspective

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Liou, James J. H.; Tzeng, Gwo-Hshiung

Human resource management (HRM) is an important issue for today’s competitive airline marketing. In this paper, we discuss a multi-objective model designed from the De Novo perspective to help airlines optimize their maintenance manpower portfolio. The effectiveness of the model and solution algorithm is demonstrated in an empirical study of the optimization of the human resources needed for airline line maintenance. Both De Novo and traditional multiple objective programming (MOP) methods are analyzed. A comparison of the results with those of traditional MOP indicates that the proposed model and solution algorithm does provide better performance and an improved human resource portfolio.

Single left coronary ostium and an anomalous prepulmonic right coronary artery in 2 dogs with congenital pulmonary valve stenosis.

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Visser, Lance C; Scansen, Brian A; Schober, Karsten E

2013-06-01

A coronary artery anomaly characterized by the presence of a single left coronary ostium with absence of the right coronary ostium and an anomalous prepulmonic right coronary artery course was observed in two dogs with concurrent congenital pulmonary valve stenosis. This unique coronary artery anatomy is similar to the previously described single right coronary ostium with anomalous prepulmonic left coronary artery, the so-called type R2A anomaly, in that an anomalous coronary artery encircles the pulmonary valve annulus. Both dogs of this report, a boxer and an English bulldog, were of breeds known to be at risk for the type R2A anomaly. As such, veterinarians should be aware that the echocardiographic presence of a left coronary ostium in a dog with pulmonary valve stenosis does not exclude the possibility of a prepulmonic coronary artery anomaly that may enhance the risk of complications during balloon pulmonary valvuloplasty. A descriptive naming convention for coronary artery anomalies in dogs is also presented, which may be preferable to the older coding classification scheme. Copyright © 2013 Elsevier B.V. All rights reserved.

A practical guide to build de-novo assemblies for single tissues of non-model organisms: the example of a Neotropical frog

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Santiago Montero-Mendieta

2017-09-01

Full Text Available Whole genome sequencing (WGS is a very valuable resource to understand the evolutionary history of poorly known species. However, in organisms with large genomes, as most amphibians, WGS is still excessively challenging and transcriptome sequencing (RNA-seq represents a cost-effective tool to explore genome-wide variability. Non-model organisms do not usually have a reference genome and the transcriptome must be assembled de-novo. We used RNA-seq to obtain the transcriptomic profile for Oreobates cruralis, a poorly known South American direct-developing frog. In total, 550,871 transcripts were assembled, corresponding to 422,999 putative genes. Of those, we identified 23,500, 37,349, 38,120 and 45,885 genes present in the Pfam, EggNOG, KEGG and GO databases, respectively. Interestingly, our results suggested that genes related to immune system and defense mechanisms are abundant in the transcriptome of O. cruralis. We also present a pipeline to assist with pre-processing, assembling, evaluating and functionally annotating a de-novo transcriptome from RNA-seq data of non-model organisms. Our pipeline guides the inexperienced user in an intuitive way through all the necessary steps to build de-novo transcriptome assemblies using readily available software and is freely available at: https://github.com/biomendi/TRANSCRIPTOME-ASSEMBLY-PIPELINE/wiki.

De novo synthesis of adenine nucleotides in different skeletal muscle fiber types

International Nuclear Information System (INIS)

Tullson, P.C.; John-Alder, H.B.; Hood, D.A.; Terjung, R.L.

1988-01-01

Management of adenine nucleotide catabolism differs among skeletal muscle fiber types. This study evaluated whether there are corresponding differences in the rates of de novo synthesis of adenine nucleotide among fiber type sections of skeletal muscle using an isolated perfused rat hindquarter preparation. Label incorporation into adenine nucleotides from the [1-14C]glycine precursor was determined and used to calculate synthesis rates based on the intracellular glycine specific radioactivity. Results show that intracellular glycine is closely related to the direct precursor pool. Rates of de novo synthesis were highest in fast-twitch red muscle (57.0 +/- 4.0, 58.2 +/- 4.4 nmol.h-1.g-1; deep red gastrocnemius and vastus lateralis), relatively high in slow-twitch red muscle (47.0 +/- 3.1; soleus), and low in fast-twitch white muscle (26.1 +/- 2.0 and 21.6 +/- 2.3; superficial white gastrocnemius and vastus lateralis). Rates for four mixed muscles were intermediate, ranging between 32.3 and 37.3. Specific de novo synthesis rates exhibited a strong correlation (r = 0.986) with muscle section citrate synthase activity. Turnover rates (de novo synthesis rate/adenine nucleotide pool size) were highest in high oxidative muscle (0.82-1.06%/h), lowest in low oxidative muscle (0.30-0.35%/h), and intermediate in mixed muscle (0.44-0.55%/h). Our results demonstrate that differences in adenine nucleotide management among fiber types extends to the process of de novo adenine nucleotide synthesis

De novo assembly and phasing of a Korean human genome.

Science.gov (United States)

Seo, Jeong-Sun; Rhie, Arang; Kim, Junsoo; Lee, Sangjin; Sohn, Min-Hwan; Kim, Chang-Uk; Hastie, Alex; Cao, Han; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok; Ryu, Hanna; Kim, Jongbum; Roh, Mira; Baek, Jeonghun; Hunkapiller, Michael W; Korlach, Jonas; Shin, Jong-Yeon; Kim, Changhoon

2016-10-13

Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of

De novo ORFs in Drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences.

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Josephine A Reinhardt

Full Text Available How non-coding DNA gives rise to new protein-coding genes (de novo genes is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution of an open reading frame. In contrast, four other de novo genes evolved a translated open reading frame and transcription within the same evolutionary interval suggesting that nascent open reading frames (proto-ORFs, while not required, can contribute to the emergence of a new de novo gene. However, none of the genes arose from proto-ORFs that existed long before expression evolved. Sequence and structural evolution of de novo genes was rapid compared to nearby genes and the structural complexity of de novo genes steadily increases over evolutionary time. Despite the fact that these genes are transcribed at a higher level in males than females, and are most strongly expressed in testes, RNAi experiments show that most of these genes are essential in both sexes during metamorphosis. This lethality suggests that protein coding de novo genes in Drosophila quickly become functionally important.

Coronary vasodilatory action after a single dose of nicorandil

NARCIS (Netherlands)

H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)

1988-01-01

textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive

Wegener's granulomatosis occurring de novo during pregnancy.

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Alfhaily, F; Watts, R; Leather, A

2009-01-01

Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients.

Role of de novo biosynthesis in ecosystem scale monoterpene emissions from a boreal Scots pine forest

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R. Taipale

2011-08-01

Full Text Available Monoterpene emissions from Scots pine have traditionally been assumed to originate as evaporation from specialized storage pools. More recently, the significance of de novo emissions, originating directly from monoterpene biosynthesis, has been recognized. To study the role of biosynthesis at the ecosystem scale, we measured monoterpene emissions from a Scots pine dominated forest in southern Finland using the disjunct eddy covariance method combined with proton transfer reaction mass spectrometry. The interpretation of the measurements was based on a correlation analysis and a hybrid emission algorithm describing both de novo and pool emissions. During the measurement period May–August 2007, the monthly medians of daytime emissions were 200, 290, 180, and 200 μg m⁻² h⁻¹. The emissions were partly light dependent, probably due to de novo biosynthesis. The emission potential for both de novo and pool emissions exhibited a decreasing summertime trend. The ratio of the de novo emission potential to the total emission potential varied between 30 % and 46 %. Although the monthly changes were not significant, the ratio always differed statistically from zero, suggesting that the role of de novo biosynthesis was observable. Given the uncertainties in this study, we conclude that more accurate estimates of the contribution of de novo emissions are required for improving monoterpene emission algorithms for Scots pine dominated forests.

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

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Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

Selecting Superior De Novo Transcriptome Assemblies: Lessons Learned by Leveraging the Best Plant Genome.

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Loren A Honaas

Full Text Available Whereas de novo assemblies of RNA-Seq data are being published for a growing number of species across the tree of life, there are currently no broadly accepted methods for evaluating such assemblies. Here we present a detailed comparison of 99 transcriptome assemblies, generated with 6 de novo assemblers including CLC, Trinity, SOAP, Oases, ABySS and NextGENe. Controlled analyses of de novo assemblies for Arabidopsis thaliana and Oryza sativa transcriptomes provide new insights into the strengths and limitations of transcriptome assembly strategies. We find that the leading assemblers generate reassuringly accurate assemblies for the majority of transcripts. At the same time, we find a propensity for assemblers to fail to fully assemble highly expressed genes. Surprisingly, the instance of true chimeric assemblies is very low for all assemblers. Normalized libraries are reduced in highly abundant transcripts, but they also lack 1000s of low abundance transcripts. We conclude that the quality of de novo transcriptome assemblies is best assessed through consideration of a combination of metrics: 1 proportion of reads mapping to an assembly 2 recovery of conserved, widely expressed genes, 3 N50 length statistics, and 4 the total number of unigenes. We provide benchmark Illumina transcriptome data and introduce SCERNA, a broadly applicable modular protocol for de novo assembly improvement. Finally, our de novo assembly of the Arabidopsis leaf transcriptome revealed ~20 putative Arabidopsis genes lacking in the current annotation.

Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

Science.gov (United States)

Tay, Wei Lin; Loh, Wann Jia; Lee, Lianne Ai Ling; Chng, Chiaw Ling

2017-01-01

We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle

DEFF Research Database (Denmark)

Agerholm, Jørgen Steen; McEvoy, Fintan; Heegaard, Steffen

2017-01-01

was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Results Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial...... chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member...... of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events...

Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance

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Thieffry Denis

2009-01-01

Full Text Available Abstract Background In breast cancer, overexpression of the transmembrane tyrosine kinase ERBB2 is an adverse prognostic marker, and occurs in almost 30% of the patients. For therapeutic intervention, ERBB2 is targeted by monoclonal antibody trastuzumab in adjuvant settings; however, de novo resistance to this antibody is still a serious issue, requiring the identification of additional targets to overcome resistance. In this study, we have combined computational simulations, experimental testing of simulation results, and finally reverse engineering of a protein interaction network to define potential therapeutic strategies for de novo trastuzumab resistant breast cancer. Results First, we employed Boolean logic to model regulatory interactions and simulated single and multiple protein loss-of-functions. Then, our simulation results were tested experimentally by producing single and double knockdowns of the network components and measuring their effects on G1/S transition during cell cycle progression. Combinatorial targeting of ERBB2 and EGFR did not affect the response to trastuzumab in de novo resistant cells, which might be due to decoupling of receptor activation and cell cycle progression. Furthermore, examination of c-MYC in resistant as well as in sensitive cell lines, using a specific chemical inhibitor of c-MYC (alone or in combination with trastuzumab, demonstrated that both trastuzumab sensitive and resistant cells responded to c-MYC perturbation. Conclusion In this study, we connected ERBB signaling with G1/S transition of the cell cycle via two major cell signaling pathways and two key transcription factors, to model an interaction network that allows for the identification of novel targets in the treatment of trastuzumab resistant breast cancer. Applying this new strategy, we found that, in contrast to trastuzumab sensitive breast cancer cells, combinatorial targeting of ERBB receptors or of key signaling intermediates does not

De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

DEFF Research Database (Denmark)

Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín

2011-01-01

Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

Automated de novo phasing and model building of coiled-coil proteins.

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Rämisch, Sebastian; Lizatović, Robert; André, Ingemar

2015-03-01

Models generated by de novo structure prediction can be very useful starting points for molecular replacement for systems where suitable structural homologues cannot be readily identified. Protein-protein complexes and de novo-designed proteins are examples of systems that can be challenging to phase. In this study, the potential of de novo models of protein complexes for use as starting points for molecular replacement is investigated. The approach is demonstrated using homomeric coiled-coil proteins, which are excellent model systems for oligomeric systems. Despite the stereotypical fold of coiled coils, initial phase estimation can be difficult and many structures have to be solved with experimental phasing. A method was developed for automatic structure determination of homomeric coiled coils from X-ray diffraction data. In a benchmark set of 24 coiled coils, ranging from dimers to pentamers with resolutions down to 2.5 Å, 22 systems were automatically solved, 11 of which had previously been solved by experimental phasing. The generated models contained 71-103% of the residues present in the deposited structures, had the correct sequence and had free R values that deviated on average by 0.01 from those of the respective reference structures. The electron-density maps were of sufficient quality that only minor manual editing was necessary to produce final structures. The method, named CCsolve, combines methods for de novo structure prediction, initial phase estimation and automated model building into one pipeline. CCsolve is robust against errors in the initial models and can readily be modified to make use of alternative crystallographic software. The results demonstrate the feasibility of de novo phasing of protein-protein complexes, an approach that could also be employed for other small systems beyond coiled coils.

De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

Science.gov (United States)

Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

2017-09-15

The thyroid gland secretes primarily tetraiodothyronine (T 4 ), and some triiodothyronine (T 3 ). Under normal physiological circumstances, only one-fifth of circulating T 3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T 3 toxicosis. Thyroidal T 4 production results from iodination of thyroglobulin (TG) at residues Tyr 5 and Tyr 130 , whereas thyroidal T 3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T 3 is formed de novo independently of deiodination from T 4 We found that upon iodination in vitro , de novo T 3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T 3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T 3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T 3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T 3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T 3 formation, contributing to the relative T 3 toxicosis of Graves' disease.

Interplay between De Novo Biosynthesis and Sequestration of Cyanogenic Glucosides in Arthropods

DEFF Research Database (Denmark)

Fürstenberg-Hägg, Joel

(Zygaenidae, Lepidoptera) both sequester (take up and accumulate) the CNglcs linamarin and lotaustralin from their food plants (Fabacea) and biosynthesize them de novo from valine and isoleucine. The presented research demonstrates that de novo biosynthesis of CNglcs in Z. filipendulae is dependent...

Novos encontros de anofelíneos em recipientes artificiais

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Oswaldo Paulo Forattini

1998-12-01

Full Text Available Assinalam-se novos encontros de anofelíneos em recipientes artificiais. Um deles diz respeito a formas imaturas de Anopheles bellator em criadouros experimentais e outro é concernente ao achado de An. albitarsis l.s., em recipiente abandonado. Tecem-se considerações sobre a pressão seletiva representada pela produção, cada vez maior, de objetos descartáveis.

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

Data on the impact of subclinical hypothyroidism on clinical outcomes following percutaneous coronary intervention

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Yonggu Lee

2018-02-01

Full Text Available This article contains the data showing the different influence of subclinical hypothyroidism (SCH on the risk of cardiovascular events after percutaneous coronary intervention (PCI in various subgroups regarding myocardial infarction, previous PCI, the stent generation, total stent length, the extent of coronary artery disease, diabetes mellitus, obesity, a lipid reduction level and a C-reactive protein level. This article also contains the data showing the association between SCH and the risk of receiving repeat PCI for in-stent restenosis or de novo coronary stenosis. The data are supplemental to our original research article titled “Impact of Subclinical Hypothyroidism on Clinical Outcomes Following Percutaneous Coronary Intervention” (Lee et al., 2017 [1].

De Novo Discovery of Structured ncRNA Motifs in Genomic Sequences

DEFF Research Database (Denmark)

Ruzzo, Walter L; Gorodkin, Jan

2014-01-01

De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphas...... on an approach based on the CMfinder CMfinder program as a case study. Applications to genomic screens for novel de novo structured ncRNA ncRNA s, including structured RNA elements in untranslated portions of protein-coding genes, are presented.......De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphasis...

On the performance of de novo pathway enrichment

DEFF Research Database (Denmark)

Batra, Richa; Alcaraz, Nicolas; Gitzhofer, Kevin

2017-01-01

De novo pathway enrichment is a powerful approach to discover previously uncharacterized molecular mechanisms in addition to already known pathways. To achieve this, condition-specific functional modules are extracted from large interaction networks. Here, we give an overview of the state...

De Novo Glutamine Synthesis

Science.gov (United States)

He, Qiao; Shi, Xinchong; Zhang, Linqi; Yi, Chang; Zhang, Xuezhen

2016-01-01

Purpose: The aim of this study was to investigate the role of de novo glutamine (Gln) synthesis in the proliferation of C6 glioma cells and its detection with 13N-ammonia. Methods: Chronic Gln-deprived C6 glioma (0.06C6) cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS) inhibitor. 13N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0.06C6 xenografts by micro–positron emission tomography (PET) scanning. The expression of GS in C6 cells and xenografts was assessed by Western blotting and immunohistochemistry, respectively. Results: The Gln-deprived C6 cells showed decreased proliferation ability but had a significant increase in GS expression. Furthermore, we found that low concentration of ammonia was sufficient to maintain the proliferation of Gln-deprived C6 cells, and 13N-ammonia uptake in C6 cells showed Gln-dependent decrease, whereas inhibition of GS markedly reduced the proliferation of C6 cells as well as the uptake of 13N-ammoina. Additionally, microPET/computed tomography exhibited that subcutaneous 0.06C6 xenografts had higher 13N-ammonia uptake and GS expression in contrast to C6 xenografts. Conclusion: De novo Gln synthesis through ammonia–glutamate reaction plays an important role in the proliferation of C6 cells. 13N-ammonia can be a potential metabolic PET tracer for Gln-dependent tumors. PMID:27118759

De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

Science.gov (United States)

Lenihan, Colin R; Liu, Sai; Deswal, Anita; Montez-Rath, Maria E; Winkelmayer, Wolfgang C

2018-03-29

Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. Retrospective observational cohort study. Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality. Copyright © 2018

A glance at quality score: implication for de novo transcriptome reconstruction of Illumina reads

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Stanley Kimbung Mbandi

2014-02-01

Full Text Available Downstream analyses of short-reads from next-generation sequencing platforms are often preceded by a pre-processing step that removes uncalled and wrongly called bases. Standard approaches rely on their associated base quality scores to retain the read or a portion of it when the score is above a predefined threshold. It is difficult to differentiate sequencing error from biological variation without a reference using quality scores. The effects of quality score based trimming have not been systematically studied in de novo transcriptome assembly. Using RNA-Seq data produced from Illumina, we teased out the effects of quality score base filtering or trimming on de novo transcriptome reconstruction. We showed that assemblies produced from reads subjected to different quality score thresholds contain truncated and missing transfrags when compared to those from untrimmed reads. Our data supports the fact that de novo assembling of untrimmed data is challenging for de Bruijn graph assemblers. However, our results indicates that comparing the assemblies from untrimmed and trimmed read subsets can suggest appropriate filtering parameters and enable selection of the optimum de novo transcriptome assembly in non-model organisms.

Três casos de hipertensão e Fístula Arteriovenosa Renal: com uma fístula de novo Tres casos de hipertención y Fístula Arteriovenosa Renal: con una fístula de novo Three cases of hypertension and Renal Arteriovenous fistula with a de novo fistula

Directory of Open Access Journals (Sweden)

Natalia Correa Vieira Melo

2009-05-01

Full Text Available Fístula Arteriovenosa Renal (FAVR é uma causa rara e potencialmente reversível de hipertensão e insuficiência renal e/ou cardíaca. O tratamento da FAVR visa preservar o máximo de parênquima renal e, concomitantemente, erradicar os sintomas e efeitos hemodinâmicos decorrentes da FAVR. No presente estudo, serão relatados três casos de FAVR, incluindo um caso de FAVR idiopática de novo, que se apresentaram com hipertensão e insuficiência renal e/ou cardíaca, e descrever a terapêutica adotada e os resultados obtidos.La Fístula Arteriovenosa Renal (FAVR es una causa rara y potencialmente reversible de hipertensión e insuficiencia renal y/o cardíaca. El tratamiento de la FAVR busca preservar el máximo de parénquima renal y, concomitantemente, erradicar los síntomas y efectos hemodinámicos resultantes de la FAVR. En el presente estudio, se relatarán tres casos de FAVR, incluyendo un caso de FAVR idiopática de novo, que se presentaron con hipertensión e insuficiencia renal y/o cardíaca, y describir la terapéutica adoptada y los resultados obtenidos.The Renal Arteriovenous Fistula (RAVF is a rare and potentially reversible cause of hypertension and kidney and/or heart failure. The treatment of RAVF aims at preserving the most of the renal parenchyma and, concomitantly, eradicating the symptoms and hemodynamic effects caused by the RAVF. The present study reports three cases of RAVF, including one case of a de novo idiopathic RAVF, which presented with hypertension and kidney and/or heart failure and describes the therapeutic measures used to treat these patients as well as the outcomes.

Photoreactivation of conversion and de novo suppressor mutation in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Bockrath, R C; Plamer, J E [Indiana Univ., Indianapolis (USA). Dept. of Microbiology

1977-04-01

Studies of mutagenesis and photoreactivation in various E.coli strains have shown that conversion mutation of a mutant containing an amber suppressor to one containing an ochre suppressor is sensitive to photoreactivation. Direct photoreactivation by photoreactivating light (PRL) after uv mutagenesis reduced mutation frequencies by a factor of about 2 for each minute of exposure during the first 5 to 8 min of exposure for cells with normal repair capacity. Conversion and potential de novo suppressor mutations were about equally sensitive. For conversion, the sensitivities to PRL were identical in the repair-normal and excisions-repair-deficient strains. For de novo suppressor mutation, the rate of mutation frequency reduction by PRL in the repair-deficient strain was about one-half that in the other strains. The results suggest that ultraviolet radiation produces both de novo suppressor mutation and conversion at the sup(E,B) locus by photoreversible pyrimidine dimers in the DNA. The causative dimers could be Thy()Cyt dimers in the transcribed strand or the non-transcribed strand, respectively.

Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease

DEFF Research Database (Denmark)

Paludan-Müller, Christian; Ahlberg, Gustav; Ghouse, Jonas

2017-01-01

BACKGROUND: De novo variants in the exome occur at a rate of 1 per individual per generation, and because of the low reproductive fitness for de novo variants causing severe disease, the likelihood of finding these as standing variations in the general population is low. Therefore, this study...... sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database. METHODS AND RESULTS: We performed a literature search for previous publications on de novo variants associated with severe arrhythmias...... trio studies (>1000 subjects). Of the monogenic variants, 11% (23/211) were present in ExAC, whereas 26% (802/3050) variants believed to increase susceptibility of disease were identified in ExAC. Monogenic de novo variants in ExAC had a total allele count of 109 and with ≈844 expected cases in Ex...

IDBA-tran: a more robust de novo de Bruijn graph assembler for transcriptomes with uneven expression levels.

Science.gov (United States)

Peng, Yu; Leung, Henry C M; Yiu, Siu-Ming; Lv, Ming-Ju; Zhu, Xin-Guang; Chin, Francis Y L

2013-07-01

RNA sequencing based on next-generation sequencing technology is effective for analyzing transcriptomes. Like de novo genome assembly, de novo transcriptome assembly does not rely on any reference genome or additional annotation information, but is more difficult. In particular, isoforms can have very uneven expression levels (e.g. 1:100), which make it very difficult to identify low-expressed isoforms. One challenge is to remove erroneous vertices/edges with high multiplicity (produced by high-expressed isoforms) in the de Bruijn graph without removing correct ones with not-so-high multiplicity from low-expressed isoforms. Failing to do so will result in the loss of low-expressed isoforms or having complicated subgraphs with transcripts of different genes mixed together due to erroneous vertices/edges. Contributions: Unlike existing tools, which remove erroneous vertices/edges with multiplicities lower than a global threshold, we use a probabilistic progressive approach to iteratively remove them with local thresholds. This enables us to decompose the graph into disconnected components, each containing a few genes, if not a single gene, while retaining many correct vertices/edges of low-expressed isoforms. Combined with existing techniques, IDBA-Tran is able to assemble both high-expressed and low-expressed transcripts and outperform existing assemblers in terms of sensitivity and specificity for both simulated and real data. http://www.cs.hku.hk/~alse/idba_tran. Supplementary data are available at Bioinformatics online.

Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

Science.gov (United States)

Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

2017-03-22

The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly.

Science.gov (United States)

Fritz-Laylin, Lillian K; Levy, Yaron Y; Levitan, Edward; Chen, Sean; Cande, W Zacheus; Lai, Elaine Y; Fulton, Chandler

2016-03-01

Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. © 2016 Wiley Periodicals, Inc.

Identifying wrong assemblies in de novo short read primary ...

Indian Academy of Sciences (India)

2016-08-05

Aug 5, 2016 ... Most of these assemblies are done using some de novo short read assemblers and other related approaches. .... benchmarking projects like Assemblathon 1, Assemblathon ... from a large insert library (at least 1000 bases).

A Pareto Algorithm for Efficient De Novo Design of Multi-functional Molecules.

Science.gov (United States)

Daeyaert, Frits; Deem, Micheal W

2017-01-01

We have introduced a Pareto sorting algorithm into Synopsis, a de novo design program that generates synthesizable molecules with desirable properties. We give a detailed description of the algorithm and illustrate its working in 2 different de novo design settings: the design of putative dual and selective FGFR and VEGFR inhibitors, and the successful design of organic structure determining agents (OSDAs) for the synthesis of zeolites. We show that the introduction of Pareto sorting not only enables the simultaneous optimization of multiple properties but also greatly improves the performance of the algorithm to generate molecules with hard-to-meet constraints. This in turn allows us to suggest approaches to address the problem of false positive hits in de novo structure based drug design by introducing structural and physicochemical constraints in the designed molecules, and by forcing essential interactions between these molecules and their target receptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

De novo structural modeling and computational sequence analysis ...

African Journals Online (AJOL)

Different bioinformatics tools and machine learning techniques were used for protein structural classification. De novo protein modeling was performed by using I-TASSER server. The final model obtained was accessed by PROCHECK and DFIRE2, which confirmed that the final model is reliable. Until complete biochemical ...

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder

DEFF Research Database (Denmark)

Hamilton, P J; Campbell, N G; Sharma, S

2013-01-01

De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution...

Sensitivity-Informed De Novo Programming for Many-Objective Water Portfolio Planning Under Uncertainty

Science.gov (United States)

Kasprzyk, J. R.; Reed, P. M.; Kirsch, B. R.; Characklis, G. W.

2009-12-01

Risk-based water supply management presents severe cognitive, computational, and social challenges to planning in a changing world. Decision aiding frameworks must confront the cognitive biases implicit to risk, the severe uncertainties associated with long term planning horizons, and the consequent ambiguities that shape how we define and solve water resources planning and management problems. This paper proposes and demonstrates a new interactive framework for sensitivity informed de novo programming. The theoretical focus of our many-objective de novo programming is to promote learning and evolving problem formulations to enhance risk-based decision making. We have demonstrated our proposed de novo programming framework using a case study for a single city’s water supply in the Lower Rio Grande Valley (LRGV) in Texas. Key decisions in this case study include the purchase of permanent rights to reservoir inflows and anticipatory thresholds for acquiring transfers of water through optioning and spot leases. A 10-year Monte Carlo simulation driven by historical data is used to provide performance metrics for the supply portfolios. The three major components of our methodology include Sobol globoal sensitivity analysis, many-objective evolutionary optimization and interactive tradeoff visualization. The interplay between these components allows us to evaluate alternative design metrics, their decision variable controls and the consequent system vulnerabilities. Our LRGV case study measures water supply portfolios’ efficiency, reliability, and utilization of transfers in the water supply market. The sensitivity analysis is used interactively over interannual, annual, and monthly time scales to indicate how the problem controls change as a function of the timescale of interest. These results have been used then to improve our exploration and understanding of LRGV costs, vulnerabilities, and the water portfolios’ critical reliability constraints. These results

Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

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Chen Xie

2012-09-01

Full Text Available Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA-Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis, which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.

Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

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Grice, Stuart J; Liu, Ji-Long; Webber, Caleb

2015-03-01

Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates

A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.

Science.gov (United States)

Koot, Bart G P; Alders, Marielle; Verheij, Joanne; Beuers, Ulrich; Cobben, Jan M

2016-04-01

Non-cirrhotic portal hypertension is characterized by histopathological abnormalities in the liver, mostly affecting small intrahepatic portal veins that cause portal hypertension in the absence of cirrhosis. It can be secondary to coagulation disorders or toxic agents. However, most cases are idiopathic non-cirrhotic portal hypertension (INCPH) and familial cases are rare. We report a family in which a father and three of his four children conceived with three different mothers are affected by INCPH. Whole exome and Sanger sequencing showed the father to have a de novo single nucleotide substitution c.1348G>C in the KCNN3 gene that was transmitted to all three of his affected offspring. The KCNN3 gene encodes small conductance calcium-activated potassium (SK) channel 3. SK channels are involved in the regulation of arterial and venous vascular tone by causing smooth muscle relaxation on activation. No data exist on the expression and function of SK channels in portal veins. The autosomal dominant inheritance in this unique pedigree and the single de novo mutation identified, strongly suggests that KCNN3 mutations have a pathogenetic role in INCPH. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

”Are CRT upgrade procedures more complex and associated with more complications than de novo CRT implantations?” A single centre experience

NARCIS (Netherlands)

Ter Horst, I. A H; Kuijpers, Y.; van t Sant, Jetske; Tuinenburg, A. E.; Cramer, M. J.; Meine, M.

2016-01-01

Objective The objective of the study was to examine whether cardiac resynchronisation therapy upgrade procedures are more complex and associated with more complications than de novo implantations. Method We retrospectively compared 134 upgrade procedures performed between 2006-2012 with a random,

76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Science.gov (United States)

2011-11-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... for Industry and Food and Drug Administration Staff; De Novo Classification Process (Evaluation of...

Efficient assembly of de novo human artificial chromosomes from large genomic loci

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Stromberg Gregory

2005-07-01

Full Text Available Abstract Background Human Artificial Chromosomes (HACs are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning, manipulating and transferring large segments of the genome. However, development of HACs for the transfer of large genomic loci into mammalian cells has been limited by difficulties in manipulating high-molecular weight DNA, as well as by the low overall frequencies of de novo HAC formation. Indeed, to date, only a small number of large (>100 kb genomic loci have been reported to be successfully packaged into de novo HACs. Results We have developed novel methodologies to enable efficient assembly of HAC vectors containing any genomic locus of interest. We report here the creation of a novel, bimolecular system based on bacterial artificial chromosomes (BACs for the construction of HACs incorporating any defined genomic region. We have utilized this vector system to rapidly design, construct and validate multiple de novo HACs containing large (100–200 kb genomic loci including therapeutically significant genes for human growth hormone (HGH, polycystic kidney disease (PKD1 and ß-globin. We report significant differences in the ability of different genomic loci to support de novo HAC formation, suggesting possible effects of cis-acting genomic elements. Finally, as a proof of principle, we have observed sustained ß-globin gene expression from HACs incorporating the entire 200 kb ß-globin genomic locus for over 90 days in the absence of selection. Conclusion Taken together, these results are significant for the development of HAC vector technology, as they enable high-throughput assembly and functional validation of HACs containing any large genomic locus. We have evaluated the impact of different genomic loci on the frequency of HAC formation and identified segments of genomic DNA that appear to facilitate de novo HAC formation. These genomic loci

The de novo assembly of mitochondrial genomes of the extinct passenger pigeon (Ectopistes migratorius with next generation sequencing.

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Chih-Ming Hung

Full Text Available The information from ancient DNA (aDNA provides an unparalleled opportunity to infer phylogenetic relationships and population history of extinct species and to investigate genetic evolution directly. However, the degraded and fragmented nature of aDNA has posed technical challenges for studies based on conventional PCR amplification. In this study, we present an approach based on next generation sequencing to efficiently sequence the complete mitochondrial genome (mitogenome of two extinct passenger pigeons (Ectopistes migratorius using de novo assembly of massive short (90 bp, paired-end or single-end reads. Although varying levels of human contamination and low levels of postmortem nucleotide lesion were observed, they did not impact sequencing accuracy. Our results demonstrated that the de novo assembly of shotgun sequence reads could be a potent approach to sequence mitogenomes, and offered an efficient way to infer evolutionary history of extinct species.

The De Novo Assembly of Mitochondrial Genomes of the Extinct Passenger Pigeon (Ectopistes migratorius) with Next Generation Sequencing

Science.gov (United States)

Hung, Chih-Ming; Lin, Rong-Chien; Chu, Jui-Hua; Yeh, Chia-Fen; Yao, Chiou-Ju; Li, Shou-Hsien

2013-01-01

The information from ancient DNA (aDNA) provides an unparalleled opportunity to infer phylogenetic relationships and population history of extinct species and to investigate genetic evolution directly. However, the degraded and fragmented nature of aDNA has posed technical challenges for studies based on conventional PCR amplification. In this study, we present an approach based on next generation sequencing to efficiently sequence the complete mitochondrial genome (mitogenome) of two extinct passenger pigeons (Ectopistes migratorius) using de novo assembly of massive short (90 bp), paired-end or single-end reads. Although varying levels of human contamination and low levels of postmortem nucleotide lesion were observed, they did not impact sequencing accuracy. Our results demonstrated that the de novo assembly of shotgun sequence reads could be a potent approach to sequence mitogenomes, and offered an efficient way to infer evolutionary history of extinct species. PMID:23437111

Isolated single coronary artery (RII-B type presenting as an inferior wall myocardial infarction: A rare clinical entity

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Ankur C. Thummar

2014-09-01

Full Text Available Isolated single coronary artery without other congenital cardiac anomalies is very rare among the different variations of anomalous coronary patterns. The prognosis in patients with single coronary varies according to the anatomic distribution and associated coronary atherosclerosis. If the left main coronary artery travels between the aorta and pulmonary arteries, it may be a cause of sudden cardiac death. We present multimodality images of a single coronary artery, in which the whole coronary system originated by a single trunk from the right sinus of Valsalva with inter-arterial course of left main coronary artery. This rare type of single coronary artery was classified as RII-B type according to Lipton's scheme of classification. A significant flow-limiting lesions were found in the right coronary artery that was successfully treated with percutaneous coronary intervention.

De novo synthesis of milk triglycerides in humans

Science.gov (United States)

Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk tha...

Single coronary artery from right aortic sinus in a very elderly patient

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Prashanth Panduranga

2016-10-01

Full Text Available In the absence of other associated cardiac anomalies, single coronary artery (SCA per se is a rare anomaly detected during coronary angiography or autopsy. Various types of SCA detected during coronary angiography have already been described. We herein report a type of SCA originating from the right sinus of Valsalva, with the right circumflex, left circumflex, and left anterior descending coronary arteries arising from the proximal part of the SCA in a 76-year-old female patient. She developed ventricular fibrillation during coronary angiography, which calls for caution while performing a coronary angiogram in such patients.

De novo-based transcriptome profiling of male-sterile and fertile watermelon lines.

Science.gov (United States)

Rhee, Sun-Ju; Kwon, Taehyung; Seo, Minseok; Jang, Yoon Jeong; Sim, Tae Yong; Cho, Seoae; Han, Sang-Wook; Lee, Gung Pyo

2017-01-01

The whole-genome sequence of watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai), a valuable horticultural crop worldwide, was released in 2013. Here, we compared a de novo-based approach (DBA) to a reference-based approach (RBA) using RNA-seq data, to aid in efforts to improve the annotation of the watermelon reference genome and to obtain biological insight into male-sterility in watermelon. We applied these techniques to available data from two watermelon lines: the male-sterile line DAH3615-MS and the male-fertile line DAH3615. Using DBA, we newly annotated 855 watermelon transcripts, and found gene functional clusters predicted to be related to stimulus responses, nucleic acid binding, transmembrane transport, homeostasis, and Golgi/vesicles. Among the DBA-annotated transcripts, 138 de novo-exclusive differentially-expressed genes (DEDEGs) related to male sterility were detected. Out of 33 randomly selected newly annotated transcripts and DEDEGs, 32 were validated by RT-qPCR. This study demonstrates the usefulness and reliability of the de novo transcriptome assembly in watermelon, and provides new insights for researchers exploring transcriptional blueprints with regard to the male sterility.

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease

International Nuclear Information System (INIS)

Nishimura, S.; Mahmarian, J.J.; Boyce, T.M.; Verani, M.S.

1991-01-01

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement

Single Coronary Artery Anomaly: A Case Report and Review of Literature.

Science.gov (United States)

Elbadawi, Ayman; Baig, Basarat; Elgendy, Islam Y; Alotaki, Erfan; Mohamed, Ahmed H; Barssoum, Kirolos; Fries, David; Khan, Muhammad; Khouzam, Rami N

2018-02-06

Single coronary artery is a rare anomaly, which is usually associated with other cardiac congenital abnormalities. A 56-year-old female presented with unstable angina. The patient reported complaints of typical chest pain on exertion few months prior to presentation, which progressed to become at rest. The pain was associated palpitations and dizziness. Past medical history was significant for hypertension and hyperlipidemia. Vital signs were stable. Physical examination was non-remarkable. Electrocardiogram showed normal sinus rhythm, with intermittent episodes of sinus bradycardia, and non-specific T-wave changes. Trans-thoracic echocardiogram showed normal left ventricular function and no segmental wall-motion abnormalities. Selective coronary angiography showed a normal left main coronary artery arising from left coronary cusp. The left main branched to a normal left anterior descending artery and to the left circumflex artery; a large vessel which supplied also the territory of the right coronary artery (RCA) through its terminal extension. Aortography showed absence of RCA with no other vessels arising from the right or non-coronary cusps. The patient was managed conservatively and discharged home with resolution of symptoms. We report a rare case of isolated single coronary artery with absent RCA. The patient presented with unstable angina, and was managed conservatively. Cardiologists should be aware of this rare condition, which carries a potential risk of sudden cardiac death.

De novo Genome Assembly and Single Nucleotide Variations for Soybean Mosaic Virus Using Soybean Seed Transcriptome Data

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Yeonhwa Jo

2017-10-01

Full Text Available Soybean is the most important legume crop in the world. Several diseases in soybean lead to serious yield losses in major soybean-producing countries. Moreover, soybean can be infected by diverse viruses. Recently, we carried out a large-scale screening to identify viruses infecting soybean using available soybean transcriptome data. Of the screened transcriptomes, a soybean transcriptome for soybean seed development analysis contains several virus-associated sequences. In this study, we identified five viruses, including soybean mosaic virus (SMV, infecting soybean by de novo transcriptome assembly followed by blast search. We assembled a nearly complete consensus genome sequence of SMV China using transcriptome data. Based on phylogenetic analysis, the consensus genome sequence of SMV China was closely related to SMV isolates from South Korea. We examined single nucleotide variations (SNVs for SMVs in the soybean seed transcriptome revealing 780 SNVs, which were evenly distributed on the SMV genome. Four SNVs, C-U, U-C, A-G, and G-A, were frequently identified. This result demonstrated the quasispecies variation of the SMV genome. Taken together, this study carried out bioinformatics analyses to identify viruses using soybean transcriptome data. In addition, we demonstrated the application of soybean transcriptome data for virus genome assembly and SNV analysis.

Iatrogenic coronary ostial stenosis of left main stem following aortic valve replacement: Visualization with optical coherence tomography

Energy Technology Data Exchange (ETDEWEB)

Khan, Muhammad A. [Department of Cardiology, Manchester Heart Centre, Manchester Royal Infirmary, M13 9WL Manchester (United Kingdom); Prati, Francesco [Interventional Cardiology, San Giovanni Hospital, Via dell’Amba Aradam 8, 00184 Rome (Italy); El-Omar, Magdi, E-mail: magdi.el-omar@cmft.nhs.uk [Department of Cardiology, Manchester Heart Centre, Manchester Royal Infirmary, M13 9WL Manchester (United Kingdom)

2013-09-15

Iatrogenic coronary ostial stenosis following aortic valve replacement (AVR) occurs in up to 3.4% of cases and usually presents within the first 6 months following surgery. We present the case of an 85 year old man who developed an acute coronary syndrome 2 months following AVR. Coronary angiography revealed a severe de novo lesion in the left main stem, which, on optical coherence tomography, was shown to be due to severe intimal hyperplasia. The most likely underlying mechanism is vessel wall trauma caused by the rigid tip cannula used for administration of cardioplegia solution. Surgeons should be aware of this possibility when administering this solution via the antegrade approach.

Uridine monophosphate synthetase enables eukaryotic de novo NAD+ biosynthesis from quinolinic acid.

Science.gov (United States)

McReynolds, Melanie R; Wang, Wenqing; Holleran, Lauren M; Hanna-Rose, Wendy

2017-07-07

NAD + biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD + biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD + biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD + biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of de novo NAD + biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact de novo biosynthesis pathway for NAD + from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD + levels and partially reversed NAD + -dependent phenotypes caused by mutation of pnc-1 , which encodes a nicotinamidase required for NAD + salvage biosynthesis, demonstrating contribution of de novo synthesis to NAD + homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD + biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD + biosynthesis creates novel possibilities for manipulating NAD + biosynthetic pathways, which is key for the future of therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Single-session versus staged procedures for elective multivessel percutaneous coronary intervention.

Science.gov (United States)

Toyota, Toshiaki; Morimoto, Takeshi; Shiomi, Hiroki; Yamaji, Kyohei; Ando, Kenji; Ono, Koh; Shizuta, Satoshi; Saito, Naritatsu; Kato, Takao; Kaji, Shuichiro; Furukawa, Yutaka; Nakagawa, Yoshihisa; Kadota, Kazushige; Horie, Minoru; Kimura, Takeshi

2018-06-01

To clarify the effect of single-session multivessel percutaneous coronary intervention (PCI) strategy relative to the staged multivessel strategy on clinical outcomes in patients with stable coronary artery disease (CAD) or non-ST-elevation acute coronary syndrome. In the Coronary REvascularisation Demonstrating Outcome Study in Kyoto PCI/coronary artery bypass grafting registry cohort-2, there were 2018 patients who underwent elective multivessel PCI. Primary outcome measure was composite of all-cause death, myocardial infarction and stroke at 5-year follow-up. Single-session multivessel PCI and staged multivessel PCI were performed in 707 patients (35.0%) and 1311 patients (65.0%), respectively. The cumulative 5-year incidence of and adjusted risk for the primary outcome measure were not significantly different between the single-session and staged groups (26.7% vs 23.0%, p=0.45; HR 0.91, 95% CI 0.72 to 1.16, p=0.47). The 30-day incidence of all-cause death was significantly higher in the single-session group than in the staged group (1.1% vs 0.2%, p=0.009). However, the causes of death in 11 patients who died within 30 days were generally not related to the procedural complications, but related to the serious clinical status before PCI. For the subgroup analyses including age, gender, extent of CAD, severe chronic kidney disease and heart failure, there was no significant interaction between the subgroup factors and the effect of the single-session strategy relative to the staged strategy for the primary outcome measure. The single-session multivessel PCI strategy was associated with at least comparable 5-year clinical outcomes compared with the staged multivessel PCI, although the prevalence of the single-session strategy was low in the present study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Illumina-based de novo transcriptome sequencing and analysis

Indian Academy of Sciences (India)

In the present study, we used Illumina HiSeq technology to perform de novo assembly of heart and musk gland transcriptomes from the Chinese forest musk deer. A total of 239,383 transcripts and 176,450 unigenes were obtained, of which 37,329 unigenes were matched to known sequences in the NCBI nonredundant ...

Identification of a novel Plasmopara halstedii elicitor protein combining de novo peptide sequencing algorithms and RACE-PCR

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Madlung Johannes

2010-05-01

Full Text Available Abstract Background Often high-quality MS/MS spectra of tryptic peptides do not match to any database entry because of only partially sequenced genomes and therefore, protein identification requires de novo peptide sequencing. To achieve protein identification of the economically important but still unsequenced plant pathogenic oomycete Plasmopara halstedii, we first evaluated the performance of three different de novo peptide sequencing algorithms applied to a protein digests of standard proteins using a quadrupole TOF (QStar Pulsar i. Results The performance order of the algorithms was PEAKS online > PepNovo > CompNovo. In summary, PEAKS online correctly predicted 45% of measured peptides for a protein test data set. All three de novo peptide sequencing algorithms were used to identify MS/MS spectra of tryptic peptides of an unknown 57 kDa protein of P. halstedii. We found ten de novo sequenced peptides that showed homology to a Phytophthora infestans protein, a closely related organism of P. halstedii. Employing a second complementary approach, verification of peptide prediction and protein identification was performed by creation of degenerate primers for RACE-PCR and led to an ORF of 1,589 bp for a hypothetical phosphoenolpyruvate carboxykinase. Conclusions Our study demonstrated that identification of proteins within minute amounts of sample material improved significantly by combining sensitive LC-MS methods with different de novo peptide sequencing algorithms. In addition, this is the first study that verified protein prediction from MS data by also employing a second complementary approach, in which RACE-PCR led to identification of a novel elicitor protein in P. halstedii.

De novo assembly of the perennial ryegrass transcriptome using an RNA-Seq strategy.

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Jacqueline D Farrell

Full Text Available Perennial ryegrass is a highly heterozygous outbreeding grass species used for turf and forage production. Heterozygosity can affect de-Bruijn graph assembly making de novo transcriptome assembly of species such as perennial ryegrass challenging. Creating a reference transcriptome from a homozygous perennial ryegrass genotype can circumvent the challenge of heterozygosity. The goals of this study were to perform RNA-sequencing on multiple tissues from a highly inbred genotype to develop a reference transcriptome. This was complemented with RNA-sequencing of a highly heterozygous genotype for SNP calling.De novo transcriptome assembly of the inbred genotype created 185,833 transcripts with an average length of 830 base pairs. Within the inbred reference transcriptome 78,560 predicted open reading frames were found of which 24,434 were predicted as complete. Functional annotation found 50,890 transcripts with a BLASTp hit from the Swiss-Prot non-redundant database, 58,941 transcripts with a Pfam protein domain and 1,151 transcripts encoding putative secreted peptides. To evaluate the reference transcriptome we targeted the high-affinity K+ transporter gene family and found multiple orthologs. Using the longest unique open reading frames as the reference sequence, 64,242 single nucleotide polymorphisms were found. One thousand sixty one open reading frames from the inbred genotype contained heterozygous sites, confirming the high degree of homozygosity.Our study has developed an annotated, comprehensive transcriptome reference for perennial ryegrass that can aid in determining genetic variation, expression analysis, genome annotation, and gene mapping.

Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

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Kyleen Luhrs

2017-01-01

Full Text Available The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62, de novo deletion copy number variations (DEL, n=74, de novo likely gene-disrupting mutations (LGDM, n=267, and children without a known genetic etiology (NON, n=2111. Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high...

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

International Nuclear Information System (INIS)

Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

1986-01-01

The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. 14 C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of 14 C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types

Melhoramento do cafeeiro: XXXVIII. Observações sobre progênies do cultivar Mundo-Novo de Coffea arabica na estação experimental de Mococa Coffee breeding: XXXVIII-observation on progenies of the Mundo-Novo cultivars of Coffea arabica in the Mococa experimental station

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Túlio R. Rocha

1980-01-01

Full Text Available Os dados analisados no experimento localizado em Mococa sobre a produtividade de 112 progênies dos cultivares Mundo-Novo S1 e S2, Bourbon-Amarelo, BourbonVermelho e Caturra-Vermelho de Coffea arabica no período de 1955 a 1971, indicaram que as de Mundo-Novo S1, de prefixos MP 474, MP 502, MP 469, MP 492 e MP 475, revelaram-se como as mais produtivas, assemelhando-se a algumas progênies 'Mundo--Novo' S2. Dentre estas, destacou-se a de prefixo MP 388-6, que atingiu o nível mais elevado de produção do experimento. As progênies de 'Mundo-Novo', em conjunto, produziram 44% a mais do que as de Bourbon-Amarelo e, estas, 60% a mais do que as de Bourbon-Vermelho e Caturra-Vermelho. A altura e o diâmetro da copa atingiram valores médios mais elevados para as progênies de 'Mundo-Novo'. Verificaram-se correlações positivas e altamente significativas entre altura média da planta e diâmetro médio da copa com a produção das progênies. As progênies mais produtivas revelaram rendimento (relação entre peso de café maduro e beneficiado de aproximadamente 6,0 e porcentagem de sementes normais, do tipo chato, acima de 80. Quanto ao tamanho das sementes do tipo chato, duas progênies 'Mundo-Novo' S1, MP 474 e MP 452, apresentaram peneira média maior, permi-tindo seleção de plantas com essa característica e com elevada produção.Coffee progenies of the Mundo-Novo cultivars of Coffea arabica were studied in an experiment located at the Mococa Experimental Station of the Instituto Agronômico in comparison with Bourbon-Amarelo, Bourbon-Vermelho and Caturra-Vermelho cultivars of the same species. During a period of 17 consecutive cropping years (1955-1971, Mundo-Novo yielded approximately 44% more than Bourbon-Amarelo and this cultivars yielded 60% more than Bourbon-Vermelho and Caturra-Vermelho. Among the 89 S1 'Mundo-Novo' progenies, MP 474, MP 502, MP 469, MP 492 and MP 475 yielded as much as the two best 'Mundo-Novo' S2 progenies. Greater

De novo point mutations in patients diagnosed with ataxic cerebral palsy.

Science.gov (United States)

Parolin Schnekenberg, Ricardo; Perkins, Emma M; Miller, Jack W; Davies, Wayne I L; D'Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O'Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis; Jackson, Mandy; Tucker, Stephen J; Németh, Andrea H

2015-07-01

Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Towards accurate de novo assembly for genomes with repeats

NARCIS (Netherlands)

Bucur, Doina

2017-01-01

De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

Engineering and introduction of de novo disulphide bridges in ...

Indian Academy of Sciences (India)

The engineeringof de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rationalmethod of protein engineering. In this study, Disulphide by Design software, homology modelling and moleculardynamics simulations were used to select appropriate amino acid pairs for ...

MÉTODO DE PRÉ-CONCENTRAÇÃO E DETERMINAÇÃO DE 17ß- ESTRADIOL: TESTE DE NOVO SORVENTE

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Samara Oliveira Sacht

2016-12-01

Full Text Available Os métodos de monitoramento ambiental para contaminantes emergentes requerem etapa de preparação das amostras para isolar os analitos de interesse. Para tal, a técnica de extração em fase sólida (SPE é a mais utilizada em conjunto com determinações por técnicas cromatográficas. Este trabalho descreve o desenvolvimento de um método analítico para a determinação da presença e medição das concentrações de um contaminante emergente de ampla ocorrência, o estrogênio 17β-estradiol. Nesta investigação foi testado o uso de um novo sorvente, de hidrofobicidade reduzida, produzido pela imobilização térmica do poli(dimetilsiloxano-co-alquilmetilsiloxano sobre partículas de sílica, Si(PDAS, resultando uma menor hidrofobicidade. Com a metodologia desenvolvida usando o novo sorvente obteve-se recuperações satisfatórias (108±16%, comprovando sua equivalência frente aos sorventes comerciais utilizando um único solvente de baixo custo (metanol na eluição.

Heterologous aggregates promote de novo prion appearance via more than one mechanism.

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Fatih Arslan

2015-01-01

Full Text Available Prions are self-perpetuating conformational variants of particular proteins. In yeast, prions cause heritable phenotypic traits. Most known yeast prions contain a glutamine (Q/asparagine (N-rich region in their prion domains. [PSI+], the prion form of Sup35, appears de novo at dramatically enhanced rates following transient overproduction of Sup35 in the presence of [PIN+], the prion form of Rnq1. Here, we establish the temporal de novo appearance of Sup35 aggregates during such overexpression in relation to other cellular proteins. Fluorescently-labeled Sup35 initially forms one or a few dots when overexpressed in [PIN+] cells. One of the dots is perivacuolar, colocalizes with the aggregated Rnq1 dot and grows into peripheral rings/lines, some of which also colocalize with Rnq1. Sup35 dots that are not near the vacuole do not always colocalize with Rnq1 and disappear by the time rings start to grow. Bimolecular fluorescence complementation failed to detect any interaction between Sup35-VN and Rnq1-VC in [PSI+][PIN+] cells. In contrast, all Sup35 aggregates, whether newly induced or in established [PSI+], completely colocalize with the molecular chaperones Hsp104, Sis1, Ssa1 and eukaryotic release factor Sup45. In the absence of [PIN+], overexpressed aggregating proteins such as the Q/N-rich Pin4C or the non-Q/N-rich Mod5 can also promote the de novo appearance of [PSI+]. Similar to Rnq1, overexpressed Pin4C transiently colocalizes with newly appearing Sup35 aggregates. However, no interaction was detected between Mod5 and Sup35 during [PSI+] induction in the absence of [PIN+]. While the colocalization of Sup35 and aggregates of Rnq1 or Pin4C are consistent with the model that the heterologous aggregates cross-seed the de novo appearance of [PSI+], the lack of interaction between Mod5 and Sup35 leaves open the possibility of other mechanisms. We also show that Hsp104 is required in the de novo appearance of [PSI+] aggregates in a [PIN

De novo assembly of plant body plan: a step ahead of Deadpool.

Science.gov (United States)

Kareem, Abdul; Radhakrishnan, Dhanya; Sondhi, Yash; Aiyaz, Mohammed; Roy, Merin V; Sugimoto, Kaoru; Prasad, Kalika

2016-08-01

While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom.

De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

DEFF Research Database (Denmark)

Myers, Candace T; McMahon, Jacinta M; Schneider, Amy L

2016-01-01

whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals...

Melhoramento do cafeeiro: XLII. Produtividade de progênies derivadas de hibridação dos cultivares Laurina e Mundo Novo Coffee breeding: XLII. Yield of progenies from crosses of Laurina and Mundo Novo cultivars of Coffea arabica L.

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Alcides Carvalho

1988-01-01

Full Text Available O cultivar Laurina de Coffea arabica L. caracteriza-se pelo pequeno porte, folhas de dimensões reduzidas, frutos afilados na base, sementes pequenas e afiladas, pequeno rendimento e reduzida produção. Apresenta, no entanto, bebida de boa qualidade e baixo teor de cafeína nas sementes. Suas principais características são controladas pela ação de um par de alelos recessivos lrlr, de acentuado efeito pleiotrópico. Devido ao atual interesse do comércio por produto de baixo teor de cafeína, iniciaram-se pesquisas tendo em vista principalmente aumentar a produtividade do 'Laurina'. Para esse fim, realizaram-se numerosas hibridações de cafeeiros do 'Laurina' com os do 'Mundo Novo' (Coffea arabica e, posteriormente, retrocruzamentos com o 'Mundo Novo'. Estudaram-se as progênies F2 e retrocruzamentos com o 'Mundo Novo' (RC em Campinas, em um experimento, anotando-se as produções por oito anos consecutivos. Separaram-se algumas progênies F2 em dois grupos, antes do plantio: normais (LrLr,Lrlr e laurina (Irlr. Como testemunhas, usaram-se progênies do 'Mundo Novo' e 'Catuaí Amarelo' de C. arabica. O conjunto de plantas F2 do grupo laurina e os retrocruzamentos tiveram produção média maior do que as plantas F2 normais, porém menor do que as testemunhas. Alguns retrocruzamentos e progênies F2 apresentaram plantas com razoável produtividade, indicando que, através de retrocruzamentos com o 'Mundo Novo', podem-se obter novos tipos comerciais com as características morfológicas do 'Laurina'. Fizeram-se considerações sobre a melhor capacidade de combinação do 'Laurina' com algumas seleções do 'Mundo Novo'.The Laurina cultivars of Coffea arabica L. has a reduced plant size, small leaves, small and pointed seeds and low yield capacity. However the seeds have a good cup quality and the desirable characteristic of low caffeine content The Laurina phenotype is supposed to be controlled by a pair of recessive alleles lrlr, with

Whole-Genome de novo Sequencing Of Quail And Grey Partridge

DEFF Research Database (Denmark)

Holm, Lars-Erik; Panitz, Frank; Burt, Dave

2011-01-01

The development in sequencing methods has made it possible to perform whole genome de novo sequencing of species without large commercial interests. Within the EU-financed QUANTOMICS project (KBBE-2A-222664), we have performed de novo sequencing of quail (Coturnix coturnix) and grey partridge...... (Perdix perdix) on a Genome Analyzer GAII (Illumina) using paired-end sequencing. The amount of generated sequences amounts to 8 to 9 Gb for each species. The analysis and assembly of the generated sequences is ongoing. Access to the whole genome sequence from these two species will enable enhanced...... comparative studies towards the chicken genome and will aid in identifying evolutionarily conserved sequences within the Galliformes. The obtained sequences from quail and partridge represent a beginning of generating the whole genome sequence for these species. The continuation of establishing the genome...

Potencial forrageiro de novos clones de capim-elefante

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Botrel Milton de Andrade

2000-01-01

Full Text Available O objetivo deste trabalho foi avaliar o comportamento de novos clones selecionados de capim-elefante. O experimento foi realizado na Embrapa Gado de Leite, em Coronel Pacheco -- MG, por um período de dois anos. Foi avaliado o potencial forrageiro de 20 clones de capim-elefante, obtidos pelo programa de melhoramento, e mais duas cultivares tradicionais (Cameroon e Taiwan A-146 usadas como testemunhas. O delineamento experimental foi o de blocos ao acaso com quatro repetições. As adubações para estabelecimento e manutenção foram realizadas de acordo com a análise do solo, visando suprir as exigências nutricionais do capim-elefante. Observaram-se diferenças significativas entre os clones, quanto ao potencial para produção de forragem, à relação folha/colmo e ao perfilhamento aéreo e basal. A maioria dos clones avaliados apresentou maior produção de matéria seca que as cultivares tradicionais, Cameroon e Taiwan A-146, durante o período seco e chuvoso. Não houve diferença significativa no teor de proteína bruta da matéria seca das cultivares controles (Cameroon e Taiwan A-146 e dos clones avaliados, em ambas as estações (águas e seca. O clone F 27-01, lançado pela Embrapa Gado de Leite com o nome de cultivar Pioneiro, destacou-se para quase todas as características agronômicas estudadas.

De novo mutations in the genome organizer CTCF cause intellectual disability

DEFF Research Database (Denmark)

Gregor, Anne; Oti, Martin; Kouwenhoven, Evelyn N

2013-01-01

An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift...... mutations and one de novo missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates...... and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three individuals with point mutations revealed deregulation of genes involved in signal transduction...

Right sided single coronary artery origin: surgical interventions without clinical consequences.

Science.gov (United States)

Hamid, Tahir; Rose, Samman; Horner, Simon

2011-11-01

Congenital coronary anomalies are uncommon and are usually diagnosed incidentally during coronary angiogram or autopsy. Isolated coronary artery anomalies and the anomalous origin of left main stem (LMS) from the proximal portion of the right coronary artery or from the right sinus of valsalva are extremely rare. A 68 years old woman with atypical chest pains was referred for risk assessment for the general anaesthesia. A stress exercise treadmill test and myocardial perfusion scan revealed evidence of mild myocardial ischemia. Her coronary angiography revealed her left coronary artery to have a single origin with the right coronary artery. There were no flowlimiting lesions. A CT aortography confirmed a retro-aortic course of the left coronary artery. She successfully underwent multiple surgical procedures under general anaesthesia including total abdominal hysterectomy, Burch colposuspension (twice) for stress incontinence, intravesical botox injection for urge incontinence and haemorrhoidectomy for recurrent rectal mucosal prolapse. Various anaesthetic agents including halothane, thiopentone, suxamethonium, pancuronium, enflurane, fentanyl, propofol and isoflurane were used without any adverse clinical consequences. She remained well on 48 months follow-up.

De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

Science.gov (United States)

Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin

2016-08-01

To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

Science.gov (United States)

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Clinical experience in coronary stenting with the Vivant Z Stent.

Science.gov (United States)

Chee, K H; Siaw, F S; Chan, C G; Chong, W P; Imran, Z A; Haizal, H K; Azman, W; Tan, K H

2005-06-01

This single centre study was designed to demonstrate feasibility, safety and efficacy of the Vivant Z stent (PFM AG, Cologne, Germany). Patients with de novo lesion were recruited. Coronary angioplasty was performed with either direct stenting or after balloon predilatation. Repeated angiogram was performed 6 months later or earlier if clinically indicated. Between January to June 2003, a total of 50 patients were recruited (mean age 55.8 +/- 9 years). A total of 52 lesions were stented successfully. Mean reference diameter was 2.77 mm (+/-0.59 SD, range 2.05-4.39 mm) with mean target lesion stenosis of 65.5% (+/-11.6 SD, range 50.1-93.3%). Forty-six lesions (88.5%) were American College of Cardiologist/American Heart Association class B/C types. Direct stenting was performed in 18 (34.6%) lesions. Mean stent diameter was 3.18 mm (+/-0.41 SD, range 2.5-4 mm), and mean stent length was 14.86 mm (+/-2.72 SD, range 9-18 mm). The procedure was complicated in only one case which involved the loss of side branch with no clinical sequelae. All treated lesions achieved Thrombolysis In Myocardial Infarction 3 flow. Mean residual diameter stenosis was 12.2% (+/-7.55 SD, range 0-22.6%) with acute gain of 1.72 mm (+/-0.50 SD, range 0.5-2.8). At 6 months, there was no major adverse cardiovascular event. Repeated angiography after 6 months showed a restenosis rate of 17% (defined as >50% diameter restenosis). Mean late loss was 0.96 mm (+/-0.48 SD) with loss index of 0.61 (+/-0.38 SD). The restenosis rate of those lesions less than 3.0 mm in diameter was 22.2% compared with 6.25% in those lesions more than 3.0 mm in diameter. The Vivant Z stent was shown to be safe and efficacious with low restenosis rate in de novo coronary artery lesion.

Optimization of de novo transcriptome assembly from high-throughput short read sequencing data improves functional annotation for non-model organisms

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Haznedaroglu Berat Z

2012-07-01

Full Text Available Abstract Background The k-mer hash length is a key factor affecting the output of de novo transcriptome assembly packages using de Bruijn graph algorithms. Assemblies constructed with varying single k-mer choices might result in the loss of unique contiguous sequences (contigs and relevant biological information. A common solution to this problem is the clustering of single k-mer assemblies. Even though annotation is one of the primary goals of a transcriptome assembly, the success of assembly strategies does not consider the impact of k-mer selection on the annotation output. This study provides an in-depth k-mer selection analysis that is focused on the degree of functional annotation achieved for a non-model organism where no reference genome information is available. Individual k-mers and clustered assemblies (CA were considered using three representative software packages. Pair-wise comparison analyses (between individual k-mers and CAs were produced to reveal missing Kyoto Encyclopedia of Genes and Genomes (KEGG ortholog identifiers (KOIs, and to determine a strategy that maximizes the recovery of biological information in a de novo transcriptome assembly. Results Analyses of single k-mer assemblies resulted in the generation of various quantities of contigs and functional annotations within the selection window of k-mers (k-19 to k-63. For each k-mer in this window, generated assemblies contained certain unique contigs and KOIs that were not present in the other k-mer assemblies. Producing a non-redundant CA of k-mers 19 to 63 resulted in a more complete functional annotation than any single k-mer assembly. However, a fraction of unique annotations remained (~0.19 to 0.27% of total KOIs in the assemblies of individual k-mers (k-19 to k-63 that were not present in the non-redundant CA. A workflow to recover these unique annotations is presented. Conclusions This study demonstrated that different k-mer choices result in various quantities

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

DEFF Research Database (Denmark)

Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

2017-01-01

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 ...

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

DEFF Research Database (Denmark)

Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki

2012-01-01

and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation...... affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3....

Incidental finding of single coronary artery in a patient with alcoholic cardiomyopathy presenting as acute heart failure.

Science.gov (United States)

McNair, Patrick; Jones, Erica; Truong, Quynh; Singh, Harsimran

Single coronary artery is a rare clinical finding. Diagnosis is typically made incidentally after the patient presents with symptoms and undergoes coronary angiography, coronary computed tomography angiography (CTA), or post-mortem during autopsy. Several high-risk features of anomalous coronary arteries have been described in the literature. Our paper describes a case of dilated alcoholic cardiomyopathy presenting as heart failure with diagnostic workup incidentally revealing single coronary artery. Copyright © 2017 Elsevier Inc. All rights reserved.

NOVOS PRODUTOS SOB O ENFOQUE DO SISTEMA DE CONSUMO E A ORIENTAÇÃO PARA O MERCADO

OpenAIRE

Mauro Calixta Tavares; Valéria Braga Pinto

2009-01-01

A orientação para o mercado tem sido abordada com suas possíveis implicações na estrutura, processos, pessoas, desenvolvimento de novos produtos, inovação e flexibilidade estratégica, entre outras possibilidades. O foco do presente capítulo é sobre sua relação com novos produtos sob a perspectiva de sistema de consumo. A partir de um estudo exploratório, os alunos de um programa de MBA, divididos em grupos, realizaram um trabalho envolvendo o consumo de vários produtos e serviços sob a perspe...

Categorização de questões de Física do novo ENEM

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Jesusney Silva Hernandes

2013-04-01

Full Text Available http://dx.doi.org/10.5007/2175-7941.2013v30n1p58 Este artigo estuda questões que envolvem Física nas provas de Ciências da Natureza e suas Tecnologias do novo ENEM. Selecionamos itens que evidenciam alguma Física nestas provas. Classificamos as questões por Competência e Habilidade segundo a matriz de referência do Exame e, através da análise de conteúdo de Bardin (2010, propusemos, para cada grupo de itens inseridos em uma dada competência, um agrupamento em categorias. A partir da observação e reflexão das categorias emergentes apresentamos ao longo do texto orientações sobre características das situações-problema que abordam alguma Física no novo ENEM. Além disso, através da análise das categorias emergentes, procuramos avaliar a aproximação das questões selecionadas com as orientações presentes nos Parâmetros Curriculares Nacionais para o Ensino Médio (PCNEM, nas Orientações Complementares aos Parâmetros Curriculares Nacionais (PCN+ e nas Orientações Curriculares para o Ensino Médio (OCEM. Percebemos que muitas orientações que surgiram das categorias emergentes atendem às orientações dos PCN, PCN+ e OCEM. Esperamos que nossa pesquisa possa contribuir para o alinhamento da prática docente com um ensino de Física inovador pautado no desenvolvimento de competências e habilidades, viabilizando melhoria de aprendizado e, consequentemente, de desempenho em Exames como o ENEM.

Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients

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Alejandro Martin-Gorgojo

2018-03-01

Full Text Available The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

Recruitable collateral blood flow index predicts coronary instent restenosis after percutaneous coronary intervention

DEFF Research Database (Denmark)

Jensen, Lisette Okkels; Thayssen, Per; Lassen, Jens Flensted

2007-01-01

AIMS: Collateral flow may influence long-term results after percutaneous coronary intervention (PCI) because of haemodynamic forces compete with the antegrade flow through the dilated lesion. The aim of the study was to assess the influence of recruitable collateral blood flow on restenosis...... in patients undergoing PCI with bare metal stents and using optimal antithrombotic treatment. METHODS AND RESULTS: In 95 patients, 95 de novo lesions were treated with PCI and a bare metal stent. Fractional flow reserve (FFR) at maximum hyperaemia induced by intravenous adenosine was determined. The pressure.......02-1.12, P = 0.016). CONCLUSION: Recruitable collateral blood flow measured during balloon inflation predicts angiographic instent restenosis in PCI patients treated with bare metal stents. Udgivelsesdato: 2007-Aug...

Hipercalcemia hipocalciúrica debida a una mutación de novo del gen del receptor sensor de calcio Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor

Directory of Open Access Journals (Sweden)

Marcelo Sarli

2004-08-01

Full Text Available El objetivo de este trabajo es presentar el inusual caso clínico de una paciente de 34 años que consultó para establecer diagnóstico de certeza y conducta terapéutica ante una hipercalcemia asintomática, detectada en un examen bioquímico de rutina. La elevación de la calcemia en ausencia de inhibición de la secreción de parathormona orientó hacia una patología paratiroidea. La persistencia de la hipercalcemia concomitante con hipocalciuria y coincidente con una relación clearance de calcio/clearance de creatinina inferior a 0.01, hicieron sospechar el diagnóstico de hipercalcemia hipocalciúrica familiar. La falta de antecedentes familiares llevó a realizar un estudio molecular de la paciente y su grupo familiar. Los resultados de los estudios nos permitieron concluir que la paciente es portadora de una mutación de novo (inactivante del gen del receptor sensor del calcio. Se incluyen los datos del estudio molecular y una breve revisión bibliográfica del tema.The aim of this paper is to refer the unusual case of a 34 years old woman who consulted because of asymptomatic hypercalcemia, detected in a biochemical routine examination. The elevated values of serum calcium without blunted parathyroid hormone secretion suggested a parathyroid pathology. The concomitance of hypocalciuria with hypercalcemia and a calcium clearance/creatinine clearance ratio less than 0.01 reverted the diagnosis of familial hypocalciuric hypercalcemia, the first option. The absence of familial background led to the molecular study of the patient and her family. The latter confirmed the diagnosis of a de novo inactivating mutation of the calcium sensing receptor. Details on the molecular study and a brief review of this subject are included.

Dual-artery stenting of a type III single coronary artery from right aortic sinus

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Shivanad Patil

2015-12-01

Full Text Available A single coronary artery presenting with stenosis in two of the three vessels arising from a common ostium is a rare anomaly Lipton et al. proposed a classification, which was modified by Yamanaka and Hobbs. In our case, a single coronary artery was giving rise to the LAD, left circumflex (LCx, and the right coronary artery (RCA. There was 80% stenosis in the ostium of the LCx. The RCA in the mid and distal segment had stenosis of 80% and 70%, respectively. We were able to successfully stent the three stenotic segments.

Spontaneous de novo vaginal adenosis resembling Bartholin’s ...

African Journals Online (AJOL)

Adebayo Alade Adewole

Spontaneous de novo vaginal adenosis resembling Bartholin's cyst: A case report ... 6 by 5 cm. The cervix, uterus, adnexa and Pouch of Douglas (POD) were normal. .... of vaginal cancer.2–4 Although, DES exposed daughters have an.

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages.

Science.gov (United States)

Rangel-Salazar, Rubén; Wickström-Lindholm, Marie; Aguilar-Salinas, Carlos A; Alvarado-Caudillo, Yolanda; Døssing, Kristina B V; Esteller, Manel; Labourier, Emmanuel; Lund, Gertrud; Nielsen, Finn C; Rodríguez-Ríos, Dalia; Solís-Martínez, Martha O; Wrobel, Katarzyna; Wrobel, Kazimierz; Zaina, Silvio

2011-11-25

We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

An 11bp region with stem formation potential is essential for de novo DNA methylation of the RPS element.

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Matthew Gentry

Full Text Available The initiation of DNA methylation in Arabidopsis is controlled by the RNA-directed DNA methylation (RdDM pathway that uses 24nt siRNAs to recruit de novo methyltransferase DRM2 to the target site. We previously described the REPETITIVE PETUNIA SEQUENCE (RPS fragment that acts as a hot spot for de novo methylation, for which it requires the cooperative activity of all three methyltransferases MET1, CMT3 and DRM2, but not the RdDM pathway. RPS contains two identical 11nt elements in inverted orientation, interrupted by a 18nt spacer, which resembles the features of a stemloop structure. The analysis of deletion/substitution derivatives of this region showed that deletion of one 11nt element RPS is sufficient to eliminate de novo methylation of RPS. In addition, deletion of a 10nt region directly adjacent to one of the 11nt elements, significantly reduced de novo methylation. When both 11nt regions were replaced by two 11nt elements with altered DNA sequence but unchanged inverted repeat homology, DNA methylation was not affected, indicating that de novo methylation was not targeted to a specific DNA sequence element. These data suggest that de novo DNA methylation is attracted by a secondary structure to which the two 11nt elements contribute, and that the adjacent 10nt region influences the stability of this structure. This resembles the recognition of structural features by DNA methyltransferases in animals and suggests that similar mechanisms exist in plants.

De novo analysis of transcriptome dynamics in the migratory locust during the development of phase traits.

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Shuang Chen

Full Text Available Locusts exhibit remarkable density-dependent phenotype (phase changes from the solitary to the gregarious, making them one of the most destructive agricultural pests. This phenotype polyphenism arises from a single genome and diverse transcriptomes in different conditions. Here we report a de novo transcriptome for the migratory locust and a comprehensive, representative core gene set. We carried out assembly of 21.5 Gb Illumina reads, generated 72,977 transcripts with N50 2,275 bp and identified 11,490 locust protein-coding genes. Comparative genomics analysis with eight other sequenced insects was carried out to identify the genomic divergence between hemimetabolous and holometabolous insects for the first time and 18 genes relevant to development was found. We further utilized the quantitative feature of RNA-seq to measure and compare gene expression among libraries. We first discovered how divergence in gene expression between two phases progresses as locusts develop and identified 242 transcripts as candidates for phase marker genes. Together with the detailed analysis of deep sequencing data of the 4(th instar, we discovered a phase-dependent divergence of biological investment in the molecular level. Solitary locusts have higher activity in biosynthetic pathways while gregarious locusts show higher activity in environmental interaction, in which genes and pathways associated with regulation of neurotransmitter activities, such as neurotransmitter receptors, synthetase, transporters, and GPCR signaling pathways, are strongly involved. Our study, as the largest de novo transcriptome to date, with optimization of sequencing and assembly strategy, can further facilitate the application of de novo transcriptome. The locust transcriptome enriches genetic resources for hemimetabolous insects and our understanding of the origin of insect metamorphosis. Most importantly, we identified genes and pathways that might be involved in locust development

De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

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Quimsiyeh Mazin

2008-12-01

Full Text Available Abstract Background In routine Assisted Reproductive Technology (ART men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG. Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9(p22.1p24 [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

De novo and salvage pathway precursor incorporation during DNA replication at the nuclear matrix

International Nuclear Information System (INIS)

Panzeter, P.L.

1988-01-01

Total nuclear DNA can be empirically subdivided into low salt-soluble (LS) DNA (75-80%), high salt-soluble (HS) DNA (18-23%), and nuclear matrix-associated (NM) DNA which remains tightly bound to the nuclear matrix (∼2%). The most-newly replicated DNA is that associated with the nuclear matrix in regenerating rat liver. Analyses of the DNA fractions after various pulse times revealed that the salvage and de novo pathway DNA precursors investigated were incorporated preferentially into NM-DNA at early pulse times, after which the radioactivity became progressively incorporated into HS- and LS-DNA, respectively. These results support two models of nuclear matrix-associated DNA replication, proposed previously, and a third model presented in this dissertation. In addition, the incorporation of de novo pathway precursors lagged significantly (> 10 minutes) behind the incorporation of precursors entering through the salvage pathway. Channeling of salvage pathway precursors to DNA replication sites would explain the more rapid uptake of salvage precursors into NM-DNA than de novo precursors. To investigate the possibility of this heretofore in vitro phenomenon, the incorporation of the salvage precursor, ( 3 H)deoxythymidine, and the de novo precursor, ( 14 C)orotic acid, into NM-DNA and dTTP was examined in regenerating rat liver. There was no significant difference between the incorporation pattern of ( 14 C)orotic acid into NM-DNA thymine and that of ( 14 C)orotic acid into soluble dTTP. Contrastingly, the salvage pathway precursor, ( 3 H)deoxythymidine, labeled NM-DNA before labeling the dTTP pool

De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

NARCIS (Netherlands)

Hoischen, Alexander; van Bon, Bregje W. M.; Rodríguez-Santiago, Benjamín; Gilissen, Christian; Vissers, Lisenka E. L. M.; de Vries, Petra; Janssen, Irene; van Lier, Bart; Hastings, Rob; Smithson, Sarah F.; Newbury-Ecob, Ruth; Kjaergaard, Susanne; Goodship, Judith; McGowan, Ruth; Bartholdi, Deborah; Rauch, Anita; Peippo, Maarit; Cobben, Jan M.; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Veltman, Joris A.; Brunner, Han G.; de Vries, Bert B. B. A.

2011-01-01

Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is

Reacções de Ciclo-Adição na Síntese de Novos Heterociclos Funcionalizados

OpenAIRE

Lopes, Susana Margarida Martins

2012-01-01

Tese de doutoramento em Química, na especialidade de Síntese Orgânica O trabalho apresentado nesta dissertação teve como objectivo principal a síntese de novos compostos heterocíclicos funcionalizados via reacções de cicloadição. Este objectivo foi alcançado através do estudo de reacções de ciclo-adição 1,3- dipolar de alenoatos, na qual estes podem funcionar como percusores de dipolos e como dipolarófilos. Uma outra vertente estudada foi a reacção de hetero-Diels-Alder de n...

Developing a de novo targeted knock-in method based on in utero electroporation into the mammalian brain.

Science.gov (United States)

Tsunekawa, Yuji; Terhune, Raymond Kunikane; Fujita, Ikumi; Shitamukai, Atsunori; Suetsugu, Taeko; Matsuzaki, Fumio

2016-09-01

Genome-editing technology has revolutionized the field of biology. Here, we report a novel de novo gene-targeting method mediated by in utero electroporation into the developing mammalian brain. Electroporation of donor DNA with the CRISPR/Cas9 system vectors successfully leads to knock-in of the donor sequence, such as EGFP, to the target site via the homology-directed repair mechanism. We developed a targeting vector system optimized to prevent anomalous leaky expression of the donor gene from the plasmid, which otherwise often occurs depending on the donor sequence. The knock-in efficiency of the electroporated progenitors reached up to 40% in the early stage and 20% in the late stage of the developing mouse brain. Furthermore, we inserted different fluorescent markers into the target gene in each homologous chromosome, successfully distinguishing homozygous knock-in cells by color. We also applied this de novo gene targeting to the ferret model for the study of complex mammalian brains. Our results demonstrate that this technique is widely applicable for monitoring gene expression, visualizing protein localization, lineage analysis and gene knockout, all at the single-cell level, in developmental tissues. © 2016. Published by The Company of Biologists Ltd.

Orbital atherectomy system in treating calcified coronary lesions: 3-Year follow-up in first human use study (ORBIT I trial)

Energy Technology Data Exchange (ETDEWEB)

Bhatt, Parloop, E-mail: parloop.bhatt@cims.me [Care Institute of Medical Sciences (CIMS), Ahmedabad 380060, Gujarat (India); Parikh, Parth, E-mail: parth.parikh@cimshospital.org [Care Institute of Medical Sciences (CIMS), Ahmedabad 380060, Gujarat (India); Patel, Apurva, E-mail: patela12@ccf.org [Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH (United States); Chag, Milan, E-mail: milan.chag@cims.me [Care Institute of Medical Sciences (CIMS), Ahmedabad 380060, Gujarat (India); Chandarana, Anish, E-mail: anish.chandarana@cims.me [Care Institute of Medical Sciences (CIMS), Ahmedabad 380060, Gujarat (India); Parikh, Roosha, E-mail: parikhr@ccf.org [Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH (United States); Parikh, Keyur, E-mail: keyur.parikh@cims.me [Care Institute of Medical Sciences (CIMS), Ahmedabad 380060, Gujarat (India)

2014-06-15

Background/Purpose: The ORBIT I trial evaluated the safety and performance of an orbital atherectomy system (OAS) in treating de novo calcified coronary lesions. Severely calcified coronary arteries pose ongoing treatment challenges. Stent placement in calcified lesions can result in stent under expansion, malapposition and procedural complications. OAS treatment may be recommended to facilitate coronary stent implantation in these difficult lesions. Materials/Methods: Fifty patients with de novo calcified coronary lesions were enrolled in the ORBIT I trial. Patients were treated with the OAS followed by stent placement. Our institution treated 33/50 patients and continued follow-up for 3 years. Results: Average age was 54.4 years and 90.9% were males. Mean lesion length was 15.9 mm. The average number of OAS devices used per patient was 1.3. Procedural success was achieved in 97% of patients. Angiographic complications were observed in five patients (two minor dissections, one major dissection and two perforations). The cumulative major adverse cardiac event (MACE) rate was 6.1% in-hospital, 9.1% at 30 days, 12.1% at 6 months, 15.2% at 2 years, and 18.2% at 3 years. The MACE rate included two in-hospital non Q-wave myocardial infarctions (MI), one additional non Q-wave MI at 30 days leading to target lesion revascularization (TLR), and three cardiac deaths. Conclusions: The ORBIT I trial suggests that OAS treatment may offer an effective method to modify calcified coronary lesion compliance to facilitate optimal stent placement in these difficult-to-treat patients with acceptable levels of safety up to 3 years post-index procedure.

Demonstration of de novo synthesis of enzymes by density labelling with stable isotopes

International Nuclear Information System (INIS)

Huebner, G.; Hirschberg, K.

1977-01-01

The technique of in vivo density labelling of proteins with H 2 18 O and 2 H 2 O has been used to investigate hormonal regulation and developmental expression of enzymes in plant cells. Buoyant density data obtained from isopycnic equilibrium centrifugation demonstrated that the cytokinine-induced nitrate reductase activity and the gibberellic acid-induced phosphatase activity in isolated embryos of Agrostemma githago are activities of enzymes synthesized de novo. The increase in alanine-specific aminopeptidase in germinating A. githago seeds is not due to de novo synthesis but to the release of preformed enzyme. On the basis of this result it is possible to apply the enzyme aminopeptidase as an internal density standard in equilibrium centrifugation. Density labelling experiments on proteins in pea cotyledons have been used to study the change in the activity of acid phosphatase, alanine-specific aminopeptidase, and peroxidase during germination. The activities of these enzymes increase in cotyledons of Pisum sativum. Density labelling by 18 O and 2 H demonstrates de novo synthesis of these three enzymes. The differential time course of enzyme induction shows the advantage of using H 2 18 O as labelling substance in cases when the enzyme was synthesized immediately at the beginning of germination. At this stage of development the amino-acid pool available for synthesis is formed principally by means of hydrolysis of storage proteins. The incorporation of 2 H into the new proteins takes place in a measurable amount at a stage of growth in which the amino acids are also synthesized de novo. The enzyme acid phosphatase of pea cotyledons was chosen to demonstrate the possibility of using the density labelling technique to detect protein turnover. (author)

Beroepsdifferentiatie in de tandheelkunde 19 : Het effect van parodontale behandeling op de mate van de novo plaquevorming

NARCIS (Netherlands)

Dahan, M; Timmerman, M F; van Winkelhoff, A J; van der Velden, U

In order to determine whether the quantity of bacteria in saliva and the degree of periodontal infection influence the speed of de novo plaque formation in periodontitis patients, 23 patients rinsed with 10 ml sterile saline. All teeth were then supragingivally and professionally cleaned, after

De novo transcriptome assembly of Setatria italica variety Taejin

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Yeonhwa Jo

2016-06-01

Full Text Available Foxtail millet (Setaria italica belonging to the family Poaceae is an important millet that is widely cultivated in East Asia. Of the cultivated millets, the foxtail millet has the longest history and is one of the main food crops in South India and China. Moreover, foxtail millet is a model plant system for biofuel generation utilizing the C4 photosynthetic pathway. In this study, we carried out de novo transcriptome assembly for the foxtail millet variety Taejin collected from Korea using next-generation sequencing. We obtained a total of 8.676 GB raw data by paired-end sequencing. The raw data in this study can be available in NCBI SRA database with accession number of SRR3406552. The Trinity program was used to de novo assemble 145,332 transcripts. Using the TransDecoder program, we predicted 82,925 putative proteins. BLASTP was performed against the Swiss-Prot protein sequence database to annotate the functions of identified proteins, resulting in 20,555 potentially novel proteins. Taken together, this study provides transcriptome data for the foxtail millet variety Taejin by RNA-Seq.

NxRepair: error correction in de novo sequence assembly using Nextera mate pairs

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Rebecca R. Murphy

2015-06-01

Full Text Available Scaffolding errors and incorrect repeat disambiguation during de novo assembly can result in large scale misassemblies in draft genomes. Nextera mate pair sequencing data provide additional information to resolve assembly ambiguities during scaffolding. Here, we introduce NxRepair, an open source toolkit for error correction in de novo assemblies that uses Nextera mate pair libraries to identify and correct large-scale errors. We show that NxRepair can identify and correct large scaffolding errors, without use of a reference sequence, resulting in quantitative improvements in the assembly quality. NxRepair can be downloaded from GitHub or PyPI, the Python Package Index; a tutorial and user documentation are also available.

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

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Rangel-Salazar Rubén

2011-11-01

Full Text Available Abstract Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20 hypermethylation in THP-1 macrophages. Here, we: 1 ask what gene expression changes accompany these epigenetic responses; 2 test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Results Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1 surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2 independent of the Dicer/micro-RNA pathway. Conclusions Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

Building a better fragment library for de novo protein structure prediction.

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Saulo H P de Oliveira

Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

Building a Better Fragment Library for De Novo Protein Structure Prediction

Science.gov (United States)

de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

2015-01-01

Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

DEFF Research Database (Denmark)

Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

2007-01-01

Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...... at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein...

REQUALIFICAÇÃO URBANA E DESPEJOS EM CENTROS NOVO E ANTIGO DE SALVADOR

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John Gledhill

Full Text Available A cidade de Salvador replica o processo de “acumulação por espoliação”, característico de um urbanismo neoliberal em todo o mundo. Neste artigo, comparamos como atua a lógica da requalificação urbana em duas zonas da cidade. A primeira é uma grande e historicamente combativa favela localizada na região que tem se tornado o mais moderno “novo centro” da cidade. Nela, a chave dos problemas são os novos projetos de mobilidade urbana e a construção de condomínios para outras classes sociais. A segunda zona é o centro colonial da cidade, que experimenta uma nova fase de gentrificação. Ali, as políticas de patrimônio histórico se encontram com outras políticas, transformando os remanescentes espaços públicos da cidade neoliberal securitizada em zonas mais seguras para turistas e residentes mais ricos. Enfatizamos o valor de um entendimento etnograficamente fundamentado para compreender o que essas mudanças significam para moradores pobres da cidade, assim como a complexidade, a heterogeneidade e a ambiguidade de suas diferentes reações.

Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates.

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Jia-Yu Chen

2015-07-01

Full Text Available While some human-specific protein-coding genes have been proposed to originate from ancestral lncRNAs, the transition process remains poorly understood. Here we identified 64 hominoid-specific de novo genes and report a mechanism for the origination of functional de novo proteins from ancestral lncRNAs with precise splicing structures and specific tissue expression profiles. Whole-genome sequencing of dozens of rhesus macaque animals revealed that these lncRNAs are generally not more selectively constrained than other lncRNA loci. The existence of these newly-originated de novo proteins is also not beyond anticipation under neutral expectation, as they generally have longer theoretical lifespan than their current age, due to their GC-rich sequence property enabling stable ORFs with lower chance of non-sense mutations. Interestingly, although the emergence and retention of these de novo genes are likely driven by neutral forces, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution, which may contribute to human-specific genetic novelties by taking advantage of existed genomic contexts.

Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

International Nuclear Information System (INIS)

Hashimoto, Muneaki; Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu; Tanaka, Akiko; Aoki, Takashi; Nara, Takeshi

2012-01-01

Highlights: ► We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. ► Disruption of the cpsII gene significantly reduced the growth of epimastigotes. ► In particular, the CPSII-null mutant severely retarded intracellular growth. ► The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes—an insect form—possess both activities, amastigotes—an intracellular replicating form of T. cruzi—are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

De novo post-pollen mitosis II tobacco pollen tube transcriptome

Czech Academy of Sciences Publication Activity Database

Hafidh, Said; Breznenová, Katarína; Honys, David

2012-01-01

Roč. 7, č. 8 (2012), s. 918-921 ISSN 1559-2316 R&D Projects: GA ČR GPP501/11/P321; GA ČR GA522/09/0858 Institutional research plan: CEZ:AV0Z50380511 Keywords : de novo pollen tube transcriptome * male gametophyte development * pollen tube growth Subject RIV: ED - Physiology

De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly.

Science.gov (United States)

Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

2015-11-26

Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

Science.gov (United States)

Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

2018-05-08

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

Norgal: extraction and de novo assembly of mitochondrial DNA from whole-genome sequencing data.

Science.gov (United States)

Al-Nakeeb, Kosai; Petersen, Thomas Nordahl; Sicheritz-Pontén, Thomas

2017-11-21

Whole-genome sequencing (WGS) projects provide short read nucleotide sequences from nuclear and possibly organelle DNA depending on the source of origin. Mitochondrial DNA is present in animals and fungi, while plants contain DNA from both mitochondria and chloroplasts. Current techniques for separating organelle reads from nuclear reads in WGS data require full reference or partial seed sequences for assembling. Norgal (de Novo ORGAneLle extractor) avoids this requirement by identifying a high frequency subset of k-mers that are predominantly of mitochondrial origin and performing a de novo assembly on a subset of reads that contains these k-mers. The method was applied to WGS data from a panda, brown algae seaweed, butterfly and filamentous fungus. We were able to extract full circular mitochondrial genomes and obtained sequence identities to the reference sequences in the range from 98.5 to 99.5%. We also assembled the chloroplasts of grape vines and cucumbers using Norgal together with seed-based de novo assemblers. Norgal is a pipeline that can extract and assemble full or partial mitochondrial and chloroplast genomes from WGS short reads without prior knowledge. The program is available at: https://bitbucket.org/kosaidtu/norgal .

Management, nutrition, and lactation performance are related to bulk tank milk de novo fatty acid concentration on northeastern US dairy farms.

Science.gov (United States)

Woolpert, M E; Dann, H M; Cotanch, K W; Melilli, C; Chase, L E; Grant, R J; Barbano, D M

2016-10-01

This study investigated the relationship of management practices, dietary characteristics, milk composition, and lactation performance with de novo fatty acid (FA) concentration in bulk tank milk from commercial dairy farms with Holstein, Jersey, and mixed-breed cows. It was hypothesized that farms with higher de novo milk FA concentrations would more commonly use management and nutrition practices known to optimize ruminal conditions that enhance de novo synthesis of milk FA. Farms (n=44) located in Vermont and northeastern New York were selected based on a history of high de novo (HDN; 26.18±0.94g/100g of FA; mean ± standard deviation) or low de novo (LDN; 24.19±1.22g/100g of FA) FA in bulk tank milk. Management practices were assessed during one visit to each farm in March or April, 2014. Total mixed ration samples were collected and analyzed for chemical composition using near infrared spectroscopy. We found no differences in days in milk at the farm level. Yield of milk fat, true protein, and de novo FA per cow per day were higher for HDN versus LDN farms. The HDN farms had lower freestall stocking density (cows/stall) than LDN farms. Additionally, tiestall feeding frequency was higher for HDN than LDN farms. No differences between HDN and LDN farms were detected for dietary dry matter, crude protein, neutral detergent fiber, starch, or percentage of forage in the diet. However, dietary ether extract was lower for HDN than LDN farms. This research indicates that overcrowded freestalls, reduced feeding frequency, and greater dietary ether extract content are associated with lower de novo FA synthesis and reduced milk fat and true protein yields on commercial dairy farms. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

DISTRIBUIÇÃO ESPACIAL DOS CASOS NOVOS DE TUBERCULOSE PULMONAR NOS MUNICÍPIOS DA REGIÃO NORTE DO BRASIL.

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Isabelle Ribeiro Barbosa

2013-10-01

Full Text Available A Tuberculose é uma endemia de grande impacto na saúde pública brasileira, e o uso de mapas para análise da espacialização de indicadores torna-se uma importante ferramenta para subsidiar as ações de controle dessa doença. O objetivo desse estudo foi analisar a distribuição espacial dos casos novos de tuberculose pulmonar na região Norte do Brasil. Trata-se de um estudo ecológico que utiliza a distribuição espacial de dados secundários de casos novos de tuberculose diagnosticados em residentes nos municípios do Norte do Brasil nos anos de 2005 a 2010. Analisou-se os principais indicadores da doença. Foram diagnosticados 41.832 casos novos de Tuberculose; o estado do Amazonas registrou a maior incidência; 84,9% dos casos foram classificados como Tuberculose pulmonar; a taxa de letalidade foi de 5,43%. Os municípios com as maiores médias anuais de casos novos foram Manaus, Belém e Ananindeua. O percentual de co-infecção com o Vírus da Imunodeficiência Humana foi de 4,17%; 1533 casos foram registrados em menores de 15 anos. A taxa de cura foi menor que 85% em mais de 80% dos municípios. Os indicadores de Tuberculose na Região Norte do Brasil estão aquém das metas preconizadas pelo Ministério da saúde, apontando para a necessidade de implementação de políticas de saúde voltadas para populações residentes em áreas de maior risco.

Identification of de novo mutations of Duchénnè/Becker muscular dystrophies in southern Spain.

Science.gov (United States)

Garcia, Susana; de Haro, Tomás; Zafra-Ceres, Mercedes; Poyatos, Antonio; Gomez-Capilla, Jose A; Gomez-Llorente, Carolina

2014-01-01

Duchénnè/Becker muscular dystrophies (DMD/BMD) are X-linked diseases, which are caused by a de novo gene mutation in one-third of affected males. The study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain) and to establish the percentage of affected males in whom a de novo gene mutation was responsible. Multiplex ligation-dependent probe amplification (MLPA) technology was applied to determine the incidence of DMD/BMD in 84 males with suspicion of the disease and 106 female relatives. Dystrophin gene exon deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son pairs studied. MLPA technology is adequate for the molecular diagnosis of DMD/BMD and establishes whether the mother carries the molecular alteration responsible for the disease, a highly relevant issue for genetic counseling.

Influence of a pressure gradient distal to implanted bare-metal stent on in-stent restenosis after percutaneous coronary intervention

DEFF Research Database (Denmark)

Jensen, Lisette Okkels; Thayssen, Per; Thuesen, Leif

2007-01-01

pullback recording in the entire length of the artery. METHODS AND RESULTS: In 98 patients with angina pectoris, 1 de novo coronary lesion was treated with a bare-metal stent. After stent implantation, pressure wire measurements (P(d)=mean hyperemic coronary pressure and P(a)=mean aortic pressure) were......-stent restenosis after 9 months. CONCLUSIONS: A residual abnormal P(d)/P(a) distal to a bare-metal stent was an independent predictor of in-stent restenosis after implantation of a coronary bare-metal stent. Udgivelsesdato: 2007-Dec-11......BACKGROUND: Fractional flow reserve predicts cardiac events after coronary stent implantation. The aim of the present study was to assess the 9-month angiographic in-stent restenosis rate in the setting of optimal stenting and a persisting gradient distal to the stent as assessed by a pressure wire...

De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

Science.gov (United States)

Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

2014-06-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

Science.gov (United States)

Guella, Ilaria; Huh, Linda; McKenzie, Marna B.; Toyota, Eric B.; Bebin, E. Martina; Thompson, Michelle L.; Cooper, Gregory M.; Evans, Daniel M.; Buerki, Sarah E.; Adam, Shelin; Van Allen, Margot I.; Nelson, Tanya N.; Connolly, Mary B.; Farrer, Matthew J.

2016-01-01

Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report. PMID:27872899

Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease

DEFF Research Database (Denmark)

Berti, Valentina; Polito, C; Borghammer, Per

2012-01-01

, recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread...... metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev...... normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore...

Análise da distribuição de focos de calor no município de Novo Progresso, Pará

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Andréia Caroline Lima Lopes

2017-06-01

Full Text Available Os incêndios são um dos principais causadores de danos aos ecossistemas florestais. Existem diversas formas de detecção dos focos de calor. Entretanto, para países com grande extensão territorial como o Brasil, é mais eficiente e barato o monitoramento por imagens de satélite. A partir disso, objetivou-se analisar a distribuição de focos de calor no município de Novo Progresso, Pará no período de 2010 a 2015, por meio de dados do monitoramento realizado por satélites de referência pertencentes ao Instituto Nacional de Pesquisas Espaciais. Após a organização das informações obtidas através do Banco de Dados de Queimadas, foram feitas análises dos fatores socioeconômicos e ambientais que intensificam o surgimento de focos de incêndios com o auxílio da literatura científica. Observou-se que os focos se concentraram na região nordeste do munícipio, ao longo da BR-163, apresentando maior ocorrência nos meses de agosto e setembro, o que pode estar relacionado com o período de estiagem do município. Analysis of the Distribution of hotspots in the Novo Progresso Town, Pará, BrazilAbstract: Fires are a major cause of damage to forest ecosystems. There are several ways of detecting hotspots. However, for countries with a vast territory as Brazil, the monitoring by satellite images is more efficient and cheaper. The aim of this study was to analyze the distribution of hotspots in the county of Novo Progresso, Pará, from 2010 to 2015 through data monitoring performed by reference satellites of the National Institute for Space Research. After organizing the information obtained through the Hotspots Database, analyses of socioeconomic and environmental factors that enhance the appearance of fire outbreaks were made with the assistance of scientific literature. It was observed that the outbreaks are concentrated in the northeastern area of the county along the BR-163, presenting higher occurrence in August and September, which

The sequence and de novo assembly of the giant panda genome

Science.gov (United States)

Li, Ruiqiang; Fan, Wei; Tian, Geng; Zhu, Hongmei; He, Lin; Cai, Jing; Huang, Quanfei; Cai, Qingle; Li, Bo; Bai, Yinqi; Zhang, Zhihe; Zhang, Yaping; Wang, Wen; Li, Jun; Wei, Fuwen; Li, Heng; Jian, Min; Li, Jianwen; Zhang, Zhaolei; Nielsen, Rasmus; Li, Dawei; Gu, Wanjun; Yang, Zhentao; Xuan, Zhaoling; Ryder, Oliver A.; Leung, Frederick Chi-Ching; Zhou, Yan; Cao, Jianjun; Sun, Xiao; Fu, Yonggui; Fang, Xiaodong; Guo, Xiaosen; Wang, Bo; Hou, Rong; Shen, Fujun; Mu, Bo; Ni, Peixiang; Lin, Runmao; Qian, Wubin; Wang, Guodong; Yu, Chang; Nie, Wenhui; Wang, Jinhuan; Wu, Zhigang; Liang, Huiqing; Min, Jiumeng; Wu, Qi; Cheng, Shifeng; Ruan, Jue; Wang, Mingwei; Shi, Zhongbin; Wen, Ming; Liu, Binghang; Ren, Xiaoli; Zheng, Huisong; Dong, Dong; Cook, Kathleen; Shan, Gao; Zhang, Hao; Kosiol, Carolin; Xie, Xueying; Lu, Zuhong; Zheng, Hancheng; Li, Yingrui; Steiner, Cynthia C.; Lam, Tommy Tsan-Yuk; Lin, Siyuan; Zhang, Qinghui; Li, Guoqing; Tian, Jing; Gong, Timing; Liu, Hongde; Zhang, Dejin; Fang, Lin; Ye, Chen; Zhang, Juanbin; Hu, Wenbo; Xu, Anlong; Ren, Yuanyuan; Zhang, Guojie; Bruford, Michael W.; Li, Qibin; Ma, Lijia; Guo, Yiran; An, Na; Hu, Yujie; Zheng, Yang; Shi, Yongyong; Li, Zhiqiang; Liu, Qing; Chen, Yanling; Zhao, Jing; Qu, Ning; Zhao, Shancen; Tian, Feng; Wang, Xiaoling; Wang, Haiyin; Xu, Lizhi; Liu, Xiao; Vinar, Tomas; Wang, Yajun; Lam, Tak-Wah; Yiu, Siu-Ming; Liu, Shiping; Zhang, Hemin; Li, Desheng; Huang, Yan; Wang, Xia; Yang, Guohua; Jiang, Zhi; Wang, Junyi; Qin, Nan; Li, Li; Li, Jingxiang; Bolund, Lars; Kristiansen, Karsten; Wong, Gane Ka-Shu; Olson, Maynard; Zhang, Xiuqing; Li, Songgang; Yang, Huanming; Wang, Jian; Wang, Jun

2013-01-01

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. PMID:20010809

Recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation Recurrência e "de novo" esteatohepatite não-alcoólica após transplante ortotópico de fígado

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Raquel F. Liermann GARCIA

2001-10-01

Full Text Available Background — Non-alcoholic steatohepatitis was coined in 1980 to describe pathological and clinical features of non-alcoholic disease associated with pathological features, commonly seen in alcoholic-liver disease itself. It is now a well-recognised cause of end-stage liver disease and a rare cause of orthotopic liver transplantation. A small number of cases with recurrent non-alcoholic steatohepatitis following liver transplantation have been reported, however de novo non-alcoholic steatohepatitis in the liver allograft is not well recognised. Aims/Results - We report four cases of non-alcoholic steatohepatitis following orthotopic liver transplantation describing the factors related with the pathology. The recurrence of fatty infiltration occurred within 21 months and transition from mild steatosis to non-alcoholic steatohepatitis and early fibrosis was observed within 60 months post transplant in all four patients. All four cases had association with one or multiples risk factors (obesity, type 2 diabetes and/or hyperlipidemia. Conclusions - Management of this risk factors may play a therapeutic role in the prevention of recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation.Racional — O termo NASH (esteatohepatite não-alcoólica foi introduzida em 1980 para descrever "características patológicas e clínicas de doença não-alcoólica observadas comumente na própria doença alcoólica". Atualmente é causa reconhecida de doença hepática crônica e rara indicação de transplante hepático. Pequeno número de casos de recurrência de NASH pós-transplante foram descritos na literatura; entretanto, de novo NASH no enxerto jamais foi relatado. Objetivos/Resultados - Reportam-se quatro casos de NASH pós-transplante, descrevendo fatores associados a esta patologia. A média de recurrência da infiltração gordurosa foi de 21 meses com transição para esteatohepatite/fibrose aos 60 meses p

Sintese fotoquimica de polipirrol em membranas microporosas de PVDF : um novo metodo para obter compositos condutores eletricos

OpenAIRE

Ruth Marlene Campomanes Santana

1995-01-01

Resumo: Este trabalho descreve em linhas gerais um novo método de obter compósitos condutores de polipirrol (PPy)/Poli(fluoreto de vinilideno) (PVDF), polimerização via luz UV induzida em presença de um adequado fotogerador de ácido (PAG), compostos tais como os sais de Ferro-areno e Trifenil sulfônio ou compostos geradores orgânicos tal como a triazina clorinada. Estudos Gravimétricos confirmados por Análise Termogravimé-trico (TGA), tem mostrado que o rendimento da polimerização insidente n...

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

Science.gov (United States)

Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

2014-01-01

In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

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Hui Miao

Full Text Available BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic. RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53 to 0.63 (95% CI, 0.60-0.66. CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort.

Science.gov (United States)

Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon

2012-04-01

The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in

Um novo modelo de previsão de demanda para inovações radicais

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Donald Neumann

2014-09-01

Full Text Available Este trabalho apresenta um novo modelo para a previsão de demanda de inovações radicais baseada em simulação de Dinâmica de Sistemas que combina conceitos do modelo de difusão de Bass e do modelo de escolha discreta. Diferentemente de outras abordagens existentes, esta proposta permite estimar não somente a fatia de mercado do produto, mas também seu comportamento no tempo (timing, a partir das preferências individuais do consumidor e das forças que as influenciam. O modelo proposto pode ser facilmente parametrizado através da Conjoint Analysis e foi testado em escala real no mercado alemão de carros elétricos. Os resultados obtidos colocam em evidência o potencial da abordagem proposta, auxiliando na compreensão dos principais fatores na escolha desse produto.

Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher

International Nuclear Information System (INIS)

Shuvalova, Yulia A.; Shirokov, Roman O.; Kaminnaya, Violetta I.; Samko, Anatoliy N.; Kaminnyi, Alexander I.

2013-01-01

Background: The EucaTax stent (EUPES) is a coronary stent with biodegradable polymer and camouflage coating that has been developed to promote the complete elution of drugs and decrease the risk of late complications. The aim of this study was to evaluate the efficacy and safety of the double-coated EUPES in patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with permanent polymer coating. Methods and Materials: The study included consecutive patient with at least 70% de novo coronary lesions in one or two native coronary arteries and who had undergone the coronary stenting using either EUPES or SES. We evaluated the 2-year major adverse cardiac events (MACE) rates, including total death (cardiac, non-cardiac), myocardial infarction (MI), target lesion revascularisation (TLR) and stent thrombosis. Results: Between 2006 and 2009 this observational, prospective, single centre study included 602 patients (282 with EUPES and 320 with SES). At 2 years, the rates of TLR (16.3% versus 6.25%; p = 0.0001) and MACE (18.4% versus 7.8%; p = 0.001) were significantly higher in the EUPES than in the SES group. The rate of TLR was significantly higher in the EUPES group compared with SES group in stenting of artery with a diameter less than 3 mm, using stent length more than 18 mm, as well as when the residual stenosis was more than 12%. Conclusions: We found that EUPES was inferior to SES during the 2-year follow-up with respect to rates of MACE and TLR that were significantly higher in the EUPES than in the SES group

Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher

Energy Technology Data Exchange (ETDEWEB)

Shuvalova, Yulia A., E-mail: shuvalovaj@mail.ru [Russian Cardiology Research and Production Complex, Department of Atherosclerosis Problems (Russian Federation); Shirokov, Roman O. [Russian Cardiology Research and Production Complex, Laboratory of Radio Vascular Therapy (Russian Federation); Kaminnaya, Violetta I. [Russian Cardiology Research and Production Complex, Department of Atherosclerosis Problems (Russian Federation); Samko, Anatoliy N. [Russian Cardiology Research and Production Complex, Laboratory of Radio Vascular Therapy (Russian Federation); Kaminnyi, Alexander I. [Russian Cardiology Research and Production Complex, Department of Atherosclerosis Problems (Russian Federation)

2013-09-15

Background: The EucaTax stent (EUPES) is a coronary stent with biodegradable polymer and camouflage coating that has been developed to promote the complete elution of drugs and decrease the risk of late complications. The aim of this study was to evaluate the efficacy and safety of the double-coated EUPES in patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with permanent polymer coating. Methods and Materials: The study included consecutive patient with at least 70% de novo coronary lesions in one or two native coronary arteries and who had undergone the coronary stenting using either EUPES or SES. We evaluated the 2-year major adverse cardiac events (MACE) rates, including total death (cardiac, non-cardiac), myocardial infarction (MI), target lesion revascularisation (TLR) and stent thrombosis. Results: Between 2006 and 2009 this observational, prospective, single centre study included 602 patients (282 with EUPES and 320 with SES). At 2 years, the rates of TLR (16.3% versus 6.25%; p = 0.0001) and MACE (18.4% versus 7.8%; p = 0.001) were significantly higher in the EUPES than in the SES group. The rate of TLR was significantly higher in the EUPES group compared with SES group in stenting of artery with a diameter less than 3 mm, using stent length more than 18 mm, as well as when the residual stenosis was more than 12%. Conclusions: We found that EUPES was inferior to SES during the 2-year follow-up with respect to rates of MACE and TLR that were significantly higher in the EUPES than in the SES group.

Intérprete surdo de língua de sinais brasileira: o novo campo de tradução / interpretação cultural e seu desafio

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Ana Regina e Souza Campello

2014-07-01

  Esse artigo é o resultado da pesquisa que trata da nova modalidade de tradução/interpretação de línguas de sinais dos intérpretes Surdos, observando a norma surda (STONE, 2009 apud SOUZA, 2010. Recentemente surgiu esse novo campo de tradução no contexto educacional do ensino a distância: o da tradução e interpretação do ator/tradutor e finalmente e intérprete de uma língua de sinais para outra língua de sinais (SEGALA, 2010; SOUZA, 2010. Estas atividades de tradução e interpretação têm sido desempenhadas por Surdos bilíngues intermodais. Exatamente por representar um novo campo de estudo, este artigo apresenta a sua constituição.

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

DEFF Research Database (Denmark)

Muona, M.; Berkovic, S. F.; Dibbens, L. M.

2015-01-01

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonicclonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo...

De-novo discovery of differentially abundant transcription factor binding sites including their positional preference.

Science.gov (United States)

Keilwagen, Jens; Grau, Jan; Paponov, Ivan A; Posch, Stefan; Strickert, Marc; Grosse, Ivo

2011-02-10

Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters. The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not been fully solved yet. Here, we present a de-novo motif discovery tool called Dispom for finding differentially abundant transcription factor binding sites that models existing positional preferences of binding sites and adjusts the length of the motif in the learning process. Evaluating Dispom, we find that its prediction performance is superior to existing tools for de-novo motif discovery for 18 benchmark data sets with planted binding sites, and for a metazoan compendium based on experimental data from micro-array, ChIP-chip, ChIP-DSL, and DamID as well as Gene Ontology data. Finally, we apply Dispom to find binding sites differentially abundant in promoters of auxin-responsive genes extracted from Arabidopsis thaliana microarray data, and we find a motif that can be interpreted as a refined auxin responsive element predominately positioned in the 250-bp region upstream of the transcription start site. Using an independent data set of auxin-responsive genes, we find in genome-wide predictions that the refined motif is more specific for auxin-responsive genes than the canonical auxin-responsive element. In general, Dispom can be used to find differentially abundant motifs in sequences of any origin. However, the positional distribution learned by Dispom is especially beneficial if all sequences are aligned to some anchor point like the transcription start site in case of promoter sequences. We demonstrate that the combination of searching for differentially abundant motifs and inferring a position distribution from the data is beneficial for de-novo motif discovery. Hence, we make the tool freely available as a component of the open

A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

Science.gov (United States)

Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

2018-05-02

The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

Transferência do fator caturra para o cultivar Mundo Novo de Coffea arabica Transfer of the CT gene to Mundo Novo cultivar

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A. Carvalho

1972-01-01

Full Text Available No presente trabalho são relatados os estudos realizados visando à introdução do gene Ct (caturra que contribui para reduzir a altura da planta, no cultivar Mundo" Novo de Coffea arabica.Estudaram-se, em ensaios de produtividade, as populações Fv F.,, F3 e F4. Nessas populações e principalmente entre os descendentes dos "caféeiros H 2077-2-5 e H 2077-2-12, foram selecionadas plantas homozigotas para os alelos Ct e também para os alelos responsáveis pela cor do fruto xc ou Xc. Essas combinações foram denominadas 'Catuaí Amarelo' e 'Catuaí Vermelho', respectivamente, e suas características são apresentadas. Os novos cultivares vêm-se mostrando de interesse econômico para as regiões cafeeiras não somente pelo porte pequeno, mas também pela produtividade, pelo vigor vegetativo e pela precocidade.The successful transfer of the Ct gene for short internode to the tall cultivar of Coffea arábica'Mundo Novo' is reported. Individual selections were carried out in the F1, F2, F3 and F4 generations. It was found that early selection in the F2 generation was quite effective. A remarkably good correlation was found between productitivity of F2 plants and the yield of the F3 and F4 generations. Plants of the F4 generation have shown reasonable uniformity and high yield in several trials. The new selections showed to be early producers. Two new cultivars were released namely 'Catuaí Amarelo' and 'Catuaí Vermelho'. The former has yellow fruits whereas the latter has red fruits. The plants are much shorter that the ones of Mundo Novo. The new cultivars have a very strong secondary and tertiary branching. Because of these characteristics Catuaí Amarelo and Catuaí Vermelho are being planted in large scale replacing the tall cultivars.

Marketing social para doação de sangue: análise da predisposição de novos doadores

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Stephanie Ingrid Souza Barboza

2014-07-01

Full Text Available Este artigo objetiva compreender os fatores motivacionais que influenciam os indivíduos a doarem sangue, com a finalidade de subsidiar as ações de marketing social orientadas à captação de novos doadores. Com base em uma revisão teórica, um modelo de hipóteses foi elaborado, para análise de influências e interações de construtos na formação da predisposição das pessoas a serem doadores de sangue. Foi feito o levantamento de campo por meio de um questionário estruturado, junto a uma amostra de 346 pessoas. Para análise, foram usadas técnicas de análise descritiva, avaliação de consistência psicométrica e modelagem de equações estruturais com estimação por mínimos quadrados parciais. Como resultados, verificou-se principalmente que há uma influência negativa do medo e positiva do grupo de referência na predisposição dos sujeitos em doar sangue. Isso indicou que as ações de marketing social para a doação de sangue são mais eficientes em incentivar novos doadores se mantiverem foco nesses dois fatores.

A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

DEFF Research Database (Denmark)

Puschmann, Andreas; Ross, Owen A; Vilariño-Güell, Carles

2009-01-01

A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cog......A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria......) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected...

Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling.

Science.gov (United States)

Scarlatti, Francesca; Sala, Giusy; Somenzi, Giulia; Signorelli, Paola; Sacchi, Nicoletta; Ghidoni, Riccardo

2003-12-01

Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L-cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA-MB-231 by activating the de novo ceramide synthesis pathway.

CIPESC® Curitiba: o trabalho da enfermagem no Distrito Bairro Novo CIPESC® Curitiba: el trabajo de enfermería en el Districto Bairro Novo CIPESC® Curitiba: the work of nursing at Bairro Novo District

Directory of Open Access Journals (Sweden)

Denise Maria Altino

2006-08-01

Full Text Available Curitiba implantou em rede o sistema Classificação Internacional das Práticas de Enfermagem em Saúde Coletiva - CIPESC®. O presente estudo objetivou identificar as atividades exercidas pelos profissionais de enfermagem nas unidades de saúde do distrito Bairro Novo de Curitiba. Trata-se de uma pesquisa descritiva em que foram entrevistados auxiliares e enfermeiras utilizando-se de um check-list. Os resultados mostram que: o acolhimento é realizado por todos; as auxiliares se ocupam mais das atividades assistencial-procedimentais; a totalidade das enfermeiras realiza consulta de enfermagem diariamente, recorrendo ao prontuário eletrônico de base CIPESC®. Conclui-se que, excetuando-se as atividades de pesquisa, houve intensificação e ampliação das atividades assistenciais sistematizadas e embasadas no trabalho cotidiano da enfermagem, intra e extramuros.Curitiba implantó el sistema Clasificación Internacional de las Prácticas de Enfermería en Salud Colectiva - CIPESC®. El presente estudio objetivó identificar las actividades ejercidas por personal de enfermería en la red de atención básica de la salud del distrito Bairro Novo, Curitiba. Ha hecho una investigación junto a los trabajadores de enfermería, recorriendo-se a check-list. Los resultados mostrarán: todos realizan el acogimiento; las auxiliares de enfermería se ocupan más de las actividades asistencial-procedimentales; todas las enfermeras realizan consulta de enfermería diariamente, utilizando-se del prontuario electrónico bases CIPESC®. En conclusión, excepto las actividades del investigación, hube intensificación y ampliación de las actividades asistenciales, que se ubican sistematizadas e embasadas en el trabajo cotidiano de la enfermería, así como la educación y planeamiento.Curitiba has been utilized system CIPESC® - International Nursing Practice Classification in Collective Health. This study goal identifies the activities of nursing staff in

Analysis of pyrimidine synthesis "de novo" intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry

NARCIS (Netherlands)

van Kuilenburg, André B. P.; van Lenthe, Henk; Löffler, Monika; van Gennip, Albert H.

2004-01-01

BACKGROUND: The concentrations of the pyrimidine "de novo" metabolites and their degradation products in urine are useful indicators for the diagnosis of an inborn error of the pyrimidine de novo pathway or a urea-cycle defect. Until now, no procedure was available that allowed the analysis of all

Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

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Hee Jeong Yoo

2015-03-01

Full Text Available Rubinstein-Taybi syndrome (RSTS is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS and Autism diagnostic interview revised (ADI-R to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

Antimicrobial peptide capsids of de novo design.

Science.gov (United States)

De Santis, Emiliana; Alkassem, Hasan; Lamarre, Baptiste; Faruqui, Nilofar; Bella, Angelo; Noble, James E; Micale, Nicola; Ray, Santanu; Burns, Jonathan R; Yon, Alexander R; Hoogenboom, Bart W; Ryadnov, Maxim G

2017-12-22

The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that-by emulating the virus architecture-assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function-they destroy bacteria on contact.

A divide-and-conquer algorithm for large-scale de novo transcriptome assembly through combining small assemblies from existing algorithms.

Science.gov (United States)

Sze, Sing-Hoi; Parrott, Jonathan J; Tarone, Aaron M

2017-12-06

While the continued development of high-throughput sequencing has facilitated studies of entire transcriptomes in non-model organisms, the incorporation of an increasing amount of RNA-Seq libraries has made de novo transcriptome assembly difficult. Although algorithms that can assemble a large amount of RNA-Seq data are available, they are generally very memory-intensive and can only be used to construct small assemblies. We develop a divide-and-conquer strategy that allows these algorithms to be utilized, by subdividing a large RNA-Seq data set into small libraries. Each individual library is assembled independently by an existing algorithm, and a merging algorithm is developed to combine these assemblies by picking a subset of high quality transcripts to form a large transcriptome. When compared to existing algorithms that return a single assembly directly, this strategy achieves comparable or increased accuracy as memory-efficient algorithms that can be used to process a large amount of RNA-Seq data, and comparable or decreased accuracy as memory-intensive algorithms that can only be used to construct small assemblies. Our divide-and-conquer strategy allows memory-intensive de novo transcriptome assembly algorithms to be utilized to construct large assemblies.

De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.

Science.gov (United States)

Stanik, Juraj; Dusatkova, Petra; Cinek, Ondrej; Valentinova, Lucia; Huckova, Miroslava; Skopkova, Martina; Dusatkova, Lenka; Stanikova, Daniela; Pura, Mikulas; Klimes, Iwar; Lebl, Jan; Gasperikova, Daniela; Pruhova, Stepanka

2014-03-01

MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A). Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing. Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo. In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.

BayesMotif: de novo protein sorting motif discovery from impure datasets.

Science.gov (United States)

Hu, Jianjun; Zhang, Fan

2010-01-18

Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of

Functional characterization of a rice de novo DNA methyltransferase, OsDRM2, expressed in Escherichia coli and yeast

Energy Technology Data Exchange (ETDEWEB)

Pang, Jinsong, E-mail: pangjs542@nenu.edu.cn [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China); Dong, Mingyue; Li, Ning; Zhao, Yanli [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China); Liu, Bao, E-mail: baoliu@nenu.edu.cn [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China)

2013-03-01

Highlights: ► A rice de novo DNA methyltransferase OsDRM2 was cloned. ► In vitro methylation activity of OsDRM2 was characterized with Escherichia coli. ► Assays of OsDRM2 in vivo methylation were done with Saccharomyces cerevisiae. ► OsDRM2 methylation activity is not preferential to any type of cytosine context. ► The activity of OsDRM2 is independent of RdDM pathway. - Abstract: DNA methylation of cytosine nucleotides is an important epigenetic modification that occurs in most eukaryotic organisms and is established and maintained by various DNA methyltransferases together with their co-factors. There are two major categories of DNA methyltransferases: de novo and maintenance. Here, we report the isolation and functional characterization of a de novo methyltransferase, named OsDRM2, from rice (Oryza sativa L.). The full-length coding region of OsDRM2 was cloned and transformed into Escherichia coli and Saccharomyces cerevisiae. Both of these organisms expressed the OsDRM2 protein, which exhibited stochastic de novo methylation activity in vitro at CG, CHG, and CHH di- and tri-nucleotide patterns. Two lines of evidence demonstrated the de novo activity of OsDRM2: (1) a 5′-CCGG-3′ containing DNA fragment that had been pre-treated with OsDRM2 protein expressed in E. coli was protected from digestion by the CG-methylation-sensitive isoschizomer HpaII; (2) methylation-sensitive amplified polymorphism (MSAP) analysis of S. cerevisiae genomic DNA from transformants that had been introduced with OsDRM2 revealed CG and CHG methylation levels of 3.92–9.12%, and 2.88–6.93%, respectively, whereas the mock control S. cerevisiae DNA did not exhibit cytosine methylation. These results were further supported by bisulfite sequencing of the 18S rRNA and EAF5 genes of the transformed S. cerevisiae, which exhibited different DNA methylation patterns, which were observed in the genomic DNA. Our findings establish that OsDRM2 is an active de novo DNA

Functional characterization of a rice de novo DNA methyltransferase, OsDRM2, expressed in Escherichia coli and yeast

International Nuclear Information System (INIS)

Pang, Jinsong; Dong, Mingyue; Li, Ning; Zhao, Yanli; Liu, Bao

2013-01-01

Highlights: ► A rice de novo DNA methyltransferase OsDRM2 was cloned. ► In vitro methylation activity of OsDRM2 was characterized with Escherichia coli. ► Assays of OsDRM2 in vivo methylation were done with Saccharomyces cerevisiae. ► OsDRM2 methylation activity is not preferential to any type of cytosine context. ► The activity of OsDRM2 is independent of RdDM pathway. - Abstract: DNA methylation of cytosine nucleotides is an important epigenetic modification that occurs in most eukaryotic organisms and is established and maintained by various DNA methyltransferases together with their co-factors. There are two major categories of DNA methyltransferases: de novo and maintenance. Here, we report the isolation and functional characterization of a de novo methyltransferase, named OsDRM2, from rice (Oryza sativa L.). The full-length coding region of OsDRM2 was cloned and transformed into Escherichia coli and Saccharomyces cerevisiae. Both of these organisms expressed the OsDRM2 protein, which exhibited stochastic de novo methylation activity in vitro at CG, CHG, and CHH di- and tri-nucleotide patterns. Two lines of evidence demonstrated the de novo activity of OsDRM2: (1) a 5′-CCGG-3′ containing DNA fragment that had been pre-treated with OsDRM2 protein expressed in E. coli was protected from digestion by the CG-methylation-sensitive isoschizomer HpaII; (2) methylation-sensitive amplified polymorphism (MSAP) analysis of S. cerevisiae genomic DNA from transformants that had been introduced with OsDRM2 revealed CG and CHG methylation levels of 3.92–9.12%, and 2.88–6.93%, respectively, whereas the mock control S. cerevisiae DNA did not exhibit cytosine methylation. These results were further supported by bisulfite sequencing of the 18S rRNA and EAF5 genes of the transformed S. cerevisiae, which exhibited different DNA methylation patterns, which were observed in the genomic DNA. Our findings establish that OsDRM2 is an active de novo DNA

A rice gene of de novo origin negatively regulates pathogen-induced defense response.

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Wenfei Xiao

Full Text Available How defense genes originated with the evolution of their specific pathogen-responsive traits remains an important problem. It is generally known that a form of duplication can generate new genes, suggesting that a new gene usually evolves from an ancestral gene. However, we show that a new defense gene in plants may evolve by de novo origination, resulting in sophisticated disease-resistant functions in rice. Analyses of gene evolution showed that this new gene, OsDR10, had homologs only in the closest relative, Leersia genus, but not other subfamilies of the grass family; therefore, it is a rice tribe-specific gene that may have originated de novo in the tribe. We further show that this gene may evolve a highly conservative rice-specific function that contributes to the regulation difference between rice and other plant species in response to pathogen infections. Biologic analyses including gene silencing, pathologic analysis, and mutant characterization by transformation showed that the OsDR10-suppressed plants enhanced resistance to a broad spectrum of Xanthomonas oryzae pv. oryzae strains, which cause bacterial blight disease. This enhanced disease resistance was accompanied by increased accumulation of endogenous salicylic acid (SA and suppressed accumulation of endogenous jasmonic acid (JA as well as modified expression of a subset of defense-responsive genes functioning both upstream and downstream of SA and JA. These data and analyses provide fresh insights into the new biologic and evolutionary processes of a de novo gene recruited rapidly.

De novo formation of centrosomes in vertebrate cells arrested during S phase

NARCIS (Netherlands)

Khodjakov, A; Rieder, CL; Sluder, G; Cassels, G; Sibon, O; Wang, CL

2002-01-01

The centrosome usually replicates in a semiconservative fashion, i.e., new centrioles form in association with preexisting "maternal" centrioles. De novo formation of centrioles has been reported for a few highly specialized cell types but it has not been seen in vertebrate somatic cells. We find

Single coronary artery originating from the right sinus Valsalva and ability to work.

Science.gov (United States)

De Rosa, Roberto; Ratti, Gennaro; Gerardi, Donato; Tedeschi, Carlo; Lamberti, Monica

2015-01-01

We present a case of a 56-year-old male electrician who was admitted to the hospital with atrial fibrillation, atypical chest pain and dyspnea. He gave a history that on the morning he had working for almost 4 hours carrying out various activities with considerable physical effort. After cardioversion, conventional coronary angiography revealed a suspect of single coronary vessel (SCA) arising from the right sinus of Valsalva. The patient underwent multislice computed tomography that showed a SCA arising from the right sinus Valsalva and dividing in Right Coronary Artery (RCA) and Left Main coronary artery (LM). The finding of posterior course of the LM without atherosclerotic has proved crucial for the expression of an opinion of working capacity even with limitation.

Função vísuo-espacial em paralisia cerebral e proposta de novo teste com a ajuda de computador

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Marilisa M. Guerreiro

1991-09-01

Full Text Available Os autores apresentam o estudo da função vísuo-espacial em uma criança com paralisia cerebral (PC. Apoiados nas teorias de Luria e Piaget, justificam a existência de tal distúrbio em PC. A criança-propósito deste estudo apresentou elementos teórico-práticos que embasaram esta idéia. Face às limitações dos testes disponíveis, propomos novo teste aplicável tanto em papel quanto em computador. Trata-se de quatro linhas dispostas equidistantemente em diferentes inclinações. A simplicidade do teste permitiu seu uso em computador, o que ampliou e aprofundou a investigação, acrescentando novos elementos ao estudo.

A rare case of de novo gigantic ovarian abscess within an endometrioma.

Science.gov (United States)

Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

2010-06-01

We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one.

Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

KAUST Repository

Takahashi, Yuta

2017-05-05

CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.

Acute heart failure with and without concomitant acute coronary syndromes: patient characteristics, management, and survival.

Science.gov (United States)

Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Nieminen, Markku S; Siirilä-Waris, Krista; Tolonen, Jukka; Tolppanen, Heli; Lassus, Johan

2014-10-01

Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03). Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Dependência de jogos eletrônicos: a possibilidade de um novo diagnóstico psiquiátrico

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Igor Lins Lemos

2012-01-01

Full Text Available CONTEXTO: A prática de jogos eletrônicos vem se desconectando do caráter meramente lúdico, podendo seu uso excessivo ser considerado um novo transtorno psiquiátrico. OBJETIVO: Realizar uma revisão da literatura científica a respeito dessa possível dependência, abordando suas principais características, a prevalência em âmbito mundial e a possibilidade de comorbidades, e avaliar a existência de procedimentos de tratamento baseados na terapia cognitivo-comportamental. MÉTODO: O estudo foi realizado nos bancos de dados da PubMed, BVS, Lilacs e SciELO, no período de 2001 a junho de 2011. RESULTADOS: Não há consenso se a dependência de jogos eletrônicos pertence ao grupo do transtorno do controle dos impulsos ou de dependência química. É visto que a prevalência dessa dependência ao redor do mundo tem média de 3%, com predominância do sexo masculino. Foram encontradas comorbidades relacionadas à dependência de jogos eletrônicos. A terapia cognitivo-comportamental já é utilizada como possível tratamento, com resultados eficazes em curto prazo. CONCLUSÃO: Apesar de a dependência de jogos eletrônicos ainda não possuir um diagnóstico específico, esse novo fenômeno deve ser discutido e aprofundado na literatura científica, buscando-se, paralelamente, um modelo eficiente de tratamento psicoterapêutico e farmacológico.

Heart failure in patients admitted for acute coronary syndromes: A report from a large national registry.

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Jeger, Raban V; Pfister, Otmar; Radovanovic, Dragana; Eberli, Franz R; Rickli, Hans; Urban, Philip; Pedrazzini, Giovanni; Stauffer, Jean-Christophe; Nossen, Jörg; Erne, Paul

2017-10-01

Data on temporal trends of heart failure (HF) in acute coronary syndrome (ACS) are scarce. Improved treatment options may have led to lower case-fatality rates (CFRs) during the last years in ACS complicated by HF. Patients of the nationwide Acute Myocardial Infarction in Switzerland (AMIS)-Plus ACS registry were analyzed from 2000 to 2014. Of 36 366 ACS patients, 3376 (9.3%) had acute or chronic HF, 2111 (5.8%) de novo acute HF (AHF), 964 (2.7%) chronic HF (CHF), and 301 (0.8%) acute decompensated CHF (ADCHF). In-hospital CFRs were highest in patients with ADCHF (32.6%) and de novo AHF (29.7%), followed by patients with CHF (12.9%) and without HF (3.2%, P acute HF. Although advances in ACS therapy improved in-hospital CFRs in patients with no HF or CHF, CFRs remained unchanged and high in patients with acute HF and ACS over the last decade. © 2017 Wiley Periodicals, Inc.

Novo método para seleção de dispersantes de última geração para concretos refratários

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Pardo A. R. F.

2002-01-01

Full Text Available O aprimoramento dos processos de instalação de concretos refratários (auto-escoamento, bombeamento, projeção, etc. tem intensificado a necessidade de otimização e controle do comportamento reológico destes materiais. A distribuição granulométrica e a concentração de sólidos, além da natureza das matérias-primas e dos aditivos químicos presentes no sistema, são os principais fatores que determinam sua reologia. Em conseqüência, a correta escolha dos agentes dispersantes é uma das tarefas fundamentais para o desenvolvimento sistemático de concretos. Contudo, os critérios tradicionalmente empregados para esta seleção, os quais se baseiam no ensaio de fluidez ou na caracterização reológica da matriz, não avaliam o comportamento do material frente às solicitações diversas de seu processamento e de sua aplicação. Sendo assim, neste trabalho foi proposto um novo método para avaliação e seleção de dispersantes, o qual analisa o comportamento do concreto desde a etapa de mistura até seu fluxo sob cisalhamento intenso. Dois aditivos usualmente empregados em concretos de alta alumina, polimetacrilato de sódio e ácido cítrico, além de dois novos dispersantes de última geração, foram então avaliados pelo método proposto e pela tradicional fluidez. Os resultados demonstraram a eficiência da nova técnica, além de atestarem o superior desempenho dos novos dispersantes avaliados.

Orbital atherectomy for the treatment of severely calcified coronary lesions: evidence, technique, and best practices.

Science.gov (United States)

Shlofmitz, Evan; Martinsen, Brad J; Lee, Michael; Rao, Sunil V; Généreux, Philippe; Higgins, Joe; Chambers, Jeffrey W; Kirtane, Ajay J; Brilakis, Emmanouil S; Kandzari, David E; Sharma, Samin K; Shlofmitz, Richard

2017-11-01

The presence of severe coronary artery calcification is associated with higher rates of angiographic complications during percutaneous coronary intervention (PCI), as well as higher major adverse cardiac events compared with non-calcified lesions. Incorporating orbital atherectomy (OAS) for effective preparation of severely calcified lesions can help maximize the benefits of PCI by attaining maximal luminal gain (or stent expansion) and improve long-term outcomes (by reducing need for revascularization). Areas covered: In this manuscript, the prevalence, risk factors, and impact of coronary artery calcification on PCI are reviewed. Based on current data and experience, the authors review orbital atherectomy technique and best practices to optimize lesion preparation. Expert Commentary: The coronary OAS is the only device approved for use in the U.S. as a treatment for de novo, severely calcified coronary lesions to facilitate stent delivery. Advantages of the device include its ease of use and a mechanism of action that treats bi-directionally, allowing for continuous blood flow during treatment, minimizing heat damage, slow flow, and subsequent need for revascularization. The OAS technique tips reviewed in this article will help inform interventional cardiologists treating patients with severely calcified lesions.

Get phases from arsenic anomalous scattering: de novo SAD phasing of two protein structures crystallized in cacodylate buffer.

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Xiang Liu

Full Text Available The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA and the human caspase-6 (Casp6, were solved by de novo arsenic single-wavelength anomalous diffraction (As-SAD phasing method. Arsenic (As, an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent arsenic group (As (V. This arsenic atom and a protein-bound zinc atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent arsenic group (As (III, in the presence of the reducing agent, dithiothreitol (DTT, and arsenic atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy atoms that generate anomalous signals, together with a few arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography.

Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

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Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

2012-01-01

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

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Marcelo Razera Baruffi

2012-01-01

Full Text Available Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19(p21.2;q13.4. Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY. Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

MERCHANDISING – ESTUDO DE CASO SOBRE UM NOVO CONCEITO DE EXPOSIÇÃO DOS PRODUTOS ADAMS NO VAREJO

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Eliseu Klein

2007-01-01

Full Text Available A partir da necessidade de se explorar melhor os espaços para exibição de confeitos em lojas do pequeno varejo, detectou-se a oportunidade de serem desenvolvidas peças expositoras que além de destacarem os produtos Adams, ainda dispusessem de um espaço extra para os varejistas exibirem outros produtos. Este estudo procurou avaliar a percepção dos resultados da mudança na forma de expor os confeitos. Buscou entender como era a situação da exposição anterior e como se deu o processo de mudança. Também teve como objetivo demonstrar a forma atual de exibição dos produtos, bem como averiguar a percepção do novo conceito de exposição por parte dos varejistas e lideranças da empresa. Realizou-se um estudo de caso exploratório, em três etapas: (1ª pesquisa bibliográfica; (2ª pesquisa de observação direta e (3ª entrevistas em profundidade, realizadas com varejistas e lideranças da Adams. Os entrevistados apontaram aspectos positivos em relação aos materiais e ao novo conceito de exposição, enfatizando a importância do merchandising no auto-serviço e sua influência nas vendas de produtos que são comprados por impulso. PALAVRAS-CHAVE: Varejo. Marketing. Merchandising. Exposição. Auto-serviço. Compra por impulso.

Lethal Ultra-Early Subarachnoid Hemorrhage Due to Rupture of De Novo Aneurysm 5 Months After Primary Aneurysmatic Subarachnoid Hemorrhage.

Science.gov (United States)

Walter, Johannes; Unterberg, Andreas W; Zweckberger, Klaus

2018-05-01

Approximately 1% of all patients surviving rupture of a cerebral aneurysm suffer from a second aneurysmatic subarachnoid hemorrhage later in their lives, 61% of which are caused by rupture of a de novo aneurysm. Latency between bleedings is usually many years, and younger patients tend to achieve better outcomes from a second subarachnoid hemorrhage. We report an unusual case of lethal ultra-early rupture of a de novo aneurysm of the anterior communicating artery only 5 months after the initial subarachnoid hemorrhage and complete coiling in a young, healthy male patient. Despite complete aneurysm obliteration, young age, and good recovery, patients may be subjected to secondary subarachnoid hemorrhages from de novo aneurysms after only a few months of the initial bleeding. Early-control magnetic resonance angiography might hence be advisable. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma.

Science.gov (United States)

Lee, Sang Hoon; Kim, Seung Up; Jang, Jeong Won; Bae, Si Hyun; Lee, Sanghun; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub

2015-01-01

Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA). This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence. This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238-7.842, Pmeasurement is a useful predictor of HCC de novo recurrence and overall survival after RFA.

Novo tipo de evaporímetro terrestre A new type of evaporimeter

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Rino N. Tosello

1960-01-01

Full Text Available No presente trabalho descreve-se um novo tipo de evaporímetro, cujo princípio de funcionamento está baseado em leis físicas que regem o fenômeno de tensão superficial. Neste tipo de evaporímetro a medida da evaporação é feita por processo volumétrieo, dispensando o emprego de mecanismos de precisão e dispendiosos. Foi feita uma análise matemática do princípio de funcionamento do novo evaporímetro, demonstrando-se oferecer exatidão plenamente satisfatória para propósitos práticos. São dados suficientes detalhes construtivos, de instalação e operação, a fim de permitir que pessoas e entidades interessadas possam reproduzi-lo e comprovar as vantagens de seu emprêgo.In this paper is described a new type of evaporimeter, the principle of operation of which is based on physical laws governing the surface tension phenomenon. The measurement of evaporation in, the new evaporimeter, described as Evaporimeter IA-58, is made by simple volumetric procedure, thus avoiding the use of precise and expensive mechanisms. A mathematical analysis of the principle of operation is made, and proves that the new evaporimeter can offer satisfactory xeaults for practical use. The operation of the new evaporimeter is very simple, since only volumetric measurements are made, with a graduated cylinder of 1000 ml, both of the added water to restore the water level to the same initial level and the outflown or excess water. It is believed that enough details are given to allow the understanding of the construction, installation and operation of the new evaporimeter, bo that interested persons or organizations could have the model reproduced and verify the advantage of its use.

Whole-genome sequencing in autism identifies hot spots for de novo germline mutation

DEFF Research Database (Denmark)

Michaelson, Jacob J.; Shi, Yujian; Gujral, Madhusudan

2012-01-01

De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We...

A simple method suitable to study de novo root organogenesis

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Xiaodong eChen

2014-05-01

Full Text Available De novo root organogenesis is the process in which adventitious roots regenerate from detached or wounded plant tissues or organs. In tissue culture, appropriate types and concentrations of plant hormones in the medium are critical for inducing adventitious roots. However, in natural conditions, regeneration from detached organs is likely to rely on endogenous hormones. To investigate the actions of endogenous hormones and the molecular mechanisms guiding de novo root organogenesis, we developed a simple method to imitate natural conditions for adventitious root formation by culturing Arabidopsis thaliana leaf explants on B5 medium without additive hormones. Here we show that the ability of the leaf explants to regenerate roots depends on the age of the leaf and on certain nutrients in the medium. Based on these observations, we provide examples of how this method can be used in different situations, and how it can be optimized. This simple method could be used to investigate the effects of various physiological and molecular changes on the regeneration of adventitious roots. It is also useful for tracing cell lineage during the regeneration process by differential interference contrast observation of -glucuronidase staining, and by live imaging of proteins labeled with fluorescent tags.

Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) Trials.

Science.gov (United States)

Planer, David; Smits, Pieter C; Kereiakes, Dean J; Kedhi, Elvin; Fahy, Martin; Xu, Ke; Serruys, Patrick W; Stone, Gregg W

2011-10-01

Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT III]; NCT00180479; SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT IV]; NCT00307047; A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: the COMPARE Trial [COMPARE]; NCT01016041). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Avifauna da Zona da Mata de Minas Gerais: municípios de Goianá e Rio Novo, com alguns registros para Coronel Pacheco e Juiz de Fora Avifaunal inventory of the "Zona da Mata" of Minas Gerais: Goianá and Rio Novo, with some records for Coronel Pacheco and Juiz de Fora municipalities

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Rômulo Ribon

2004-04-01

Full Text Available A partir da oportunidade criada pelos Estudos de Impacto Ambiental para implantação do Aeroporto Regional da Zona da Mata, fez-se a caracterização qualitativa preliminar da avifauna dos municípios de Goianá e Rio Novo, na Zona da Mata, sudeste de Minas Gerais. Alguns registros para áreas limítrofes dos municípios de Juiz de Fora e Coronel Pacheco são também fornecidos. A região, originalmente coberta por Mata Atlântica, é hoje composta por um mosaico de pastagens, fragmentos florestais, pomares domésticos e ambientes limícolas. Foram registradas 185 espécies de aves, sendo os ambientes de mata os mais ricos em espécies. Neste artigo serão dadas informações sobre o habitat, o método de registro das espécies e, para algumas delas, sobre a atividade reprodutiva. A presença da planície de inundação do rio Novo proporciona ambiente para espécies normalmente pouco abundantes no restante da Zona da Mata. Destacam-se a extinção local de pelo menos duas espécies registradas no século XIX, a presença de algumas aves ameaçadas de extinção e a importância de estudos de impacto ambiental como oportunidade, muitas vezes perdida, para obtenção de informações biológicas.The support provided by the Environmental Impact Assessment for the construction of the Zona da Mata Regional Airport allowed the conduction of a qualitative sampling of the bird community at Goianá and Rio Novo municipalities, in the "Zona da Mata" region, southeastern Minas Gerais, Brazil. Some records for neighboring areas at Juiz de Fora and Coronel Pacheco municipalities are also given. The region is located in the Semidecidual Lowland Atlantic Forest domain but the current landscape is a mosaic of artificial pasturelands, secondary forest fragments, small orchards around farms' headquarters, small ponds for fish farming, and marshes at the Rio Novo floodplain. We recorded 185 bird species with the forest fragments being the richest habitat

Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

International Nuclear Information System (INIS)

Haigh, Cathryn L.; Drew, Simon C.

2015-01-01

The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation

Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

Energy Technology Data Exchange (ETDEWEB)

Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Drew, Simon C., E-mail: sdrew@unimelb.edu.au [Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010 (Australia)

2015-06-05

The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.

Marketing de Novos Produtos: Lançamento e Inovação

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Adriana Conceicao Dutra

2014-12-01

Full Text Available Atualmente as empresas lançam um produto com o objetivo de permanecerem por mais tempo no mercado. Embora muitas empresas fracassassem ao lançarem um produto, seria um mito dizer que as maiorias dos novos produtos fracassam ou que seu sucesso vai de acordo com sua atratividade. A modernização traz consigo as premissas, a eficiência, a qualidade e a produtividade, que de certa forma impõem uma carga à sociedade como um todo. Superar as expectativas dos consumidores, por meio de produtos e serviços inovadores, assegura vantagens competitivas e permite às empresas a ocupação de posições de liderança, em mercados altamente competitivos.

Differences in Recurrence Rate and De Novo Incontinence after Endoscopic Treatment of Vesicourethral Stenosis and Bladder Neck Stenosis

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Jennifer Kranz

2017-08-01

Full Text Available ObjectivesThe objective of this study was to compare the recurrence rate and de novo incontinence after endoscopic treatment of vesicourethral stenosis (VUS after radical prostatectomy (RP and for bladder neck stenosis (BNS after transurethral resection of the prostate (TURP.MethodsRetrospective analysis of patients treated endoscopically for VUS after RP or for BNS after TURP at three German tertiary care centers between March 2009 and June 2016. Investigated endpoints were recurrence rate and de novo incontinence. Chi-squared tests and t-tests were used to model the differences between groups.ResultsA total of 147 patients underwent endoscopic therapy for VUS (59.2% or BNS (40.8%. Mean age was 68.3 years (range 44–86, mean follow-up 27.1 months (1–98. Mean time to recurrence after initial therapy was 23.9 months (1–156, mean time to recurrence after prior endoscopic therapy for VUS or BNS was 12.0 months (1–159. Patients treated for VUS underwent significantly more often radiotherapy prior to endoscopic treatment (33.3 vs. 13.3%; p = 0.006 and the recurrence rate was significantly higher (59.8 vs. 41.7%; p = 0.031. The overall success rate of TUR for VUS was 40.2%, success rate of TUR for BNS was 58.3%. TUR for BNS is significantly more successful (p = 0.031. The mean number of TUR for BNS vs. TUR for VUS in successful cases was 1.5 vs. 1.8, which was not significantly different. The rate of de novo incontinence was significantly higher in patients treated for VUS (13.8 vs. 1.7%; p = 0.011. After excluding those patients with radiotherapy prior to endoscopic treatment, the recurrence rate did not differ significantly between both groups (60.3% for VUS vs. 44.2% for BNS; p = 0.091, whereas the rate of de novo incontinence (13.8 for VUS vs. 0% for BNS; p = 0.005 stayed significantly higher in patients treated for VUS.ConclusionMost patients with BNS are successfully treated endoscopically. In patients with

Origins of De Novo Genes in Human and Chimpanzee.

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Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

2015-12-01

The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

Characterization and analysis of a de novo transcriptome from the pygmy grasshopper Tetrix japonica.

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Qiu, Zhongying; Liu, Fei; Lu, Huimeng; Huang, Yuan

2017-05-01

The pygmy grasshopper Tetrix japonica is a common insect distributed throughout the world, and it has the potential for use in studies of body colour polymorphism, genomics and the biology of Tetrigoidea (Insecta: Orthoptera). However, limited biological information is available for this insect. Here, we conducted a de novo transcriptome study of adult and larval T. japonica to provide a better understanding of its gene expression and develop genomic resources for future work. We sequenced and explored the characteristics of the de novo transcriptome of T. japonica using Illumina HiSeq 2000 platform. A total of 107 608 206 paired-end clean reads were assembled into 61 141 unigenes using the trinity software; the mean unigene size was 771 bp, and the N50 length was 1238 bp. A total of 29 225 unigenes were functionally annotated to the NCBI nonredundant protein sequences (Nr), NCBI nonredundant nucleotide sequences (Nt), a manually annotated and reviewed protein sequence database (Swiss-Prot), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A large number of putative genes that are potentially involved in pigment pathways, juvenile hormone (JH) metabolism and signalling pathways were identified in the T. japonica transcriptome. Additionally, 165 769 and 156 796 putative single nucleotide polymorphisms occurred in the adult and larvae transcriptomes, respectively, and a total of 3162 simple sequence repeats were detected in this assembly. This comprehensive transcriptomic data for T. japonica will provide a usable resource for gene predictions, signalling pathway investigations and molecular marker development for this species and other pygmy grasshoppers. © 2016 John Wiley & Sons Ltd.

Improved protein quality in transgenic soybean expressing a de novo synthetic protein, MB-16.

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Zhang, Yunfang; Schernthaner, Johann; Labbé, Natalie; Hefford, Mary A; Zhao, Jiping; Simmonds, Daina H

2014-06-01

To improve soybean [Glycine max (L.) Merrill] seed nutritional quality, a synthetic gene, MB-16 was introduced into the soybean genome to boost seed methionine content. MB-16, an 11 kDa de novo protein enriched in the essential amino acids (EAAs) methionine, threonine, lysine and leucine, was originally developed for expression in rumen bacteria. For efficient seed expression, constructs were designed using the soybean codon bias, with and without the KDEL ER retention sequence, and β-conglycinin or cruciferin seed specific protein storage promoters. Homozygous lines, with single locus integrations, were identified for several transgenic events. Transgene transmission and MB-16 protein expression were confirmed to the T5 and T7 generations, respectively. Quantitative RT-PCR analysis of developing seed showed that the transcript peaked in growing seed, 5-6 mm long, remained at this peak level to the full-sized green seed and then was significantly reduced in maturing yellow seed. Transformed events carrying constructs with the rumen bacteria codon preference showed the same transcription pattern as those with the soybean codon preference, but the transcript levels were lower at each developmental stage. MB-16 protein levels, as determined by immunoblots, were highest in full-sized green seed but the protein virtually disappeared in mature seed. However, amino acid analysis of mature seed, in the best transgenic line, showed a significant increase of 16.2 and 65.9 % in methionine and cysteine, respectively, as compared to the parent. This indicates that MB-16 elevated the sulfur amino acids, improved the EAA seed profile and confirms that a de novo synthetic gene can enhance the nutritional quality of soybean.

Online Angiography Image-Based FFR Assessment During Coronary Catheterization: A Single-Center Study.

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Kornowski, Ran; Vaknin-Assa, Hana; Assali, Abid; Greenberg, Gabriel; Valtzer, Orna; Lavi, Ifat

2018-03-15

To assess the diagnostic performance of angiography-derived fractional flow reserve (FFRangio) measurements in patients with stable coronary artery disease when used online in the catheterization laboratory during routine coronary angiography. FFR, an index of the hemodynamic severity of coronary stenosis, is derived from invasive measurements using a pressure-monitoring guidewire and hyperemic stimulus. While FFR is the gold standard, it remains under-utilized. FFRangio may have several advantages owing to the reduced operator time, no wire-related or procedural complications, and no need for administration of vasodilators. FFRangio is a novel technology that uses a patient's hemodynamic data and routine angiograms to generate FFR values at each point along the coronary tree. We present the online application of the system where FFRangio was successfully used in the catheterization laboratory during routine coronary angiography and compared to invasive FFR. Fifty-three patients (79% men) and 60 coronary lesions were analyzed. Values derived using FFRangio ranged from 0.58-0.96 and correlated closely (Pearson's correlation coefficient, r=0.91; Psystem. In this single-center experience, FFRangio values showed high correlation rates to invasive FFR.

De Novo Assembly and Characterization of the Transcriptome of Grasshopper Shirakiacris shirakii

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Zhongying Qiu

2016-07-01

Full Text Available Background: The grasshopper Shirakiacris shirakii is an important agricultural pest and feeds mainly on gramineous plants, thereby causing economic damage to a wide range of crops. However, genomic information on this species is extremely limited thus far, and transcriptome data relevant to insecticide resistance and pest control are also not available. Methods: The transcriptome of S. shirakii was sequenced using the Illumina HiSeq platform, and we de novo assembled the transcriptome. Results: Its sequencing produced a total of 105,408,878 clean reads, and the de novo assembly revealed 74,657 unigenes with an average length of 680 bp and N50 of 1057 bp. A total of 28,173 unigenes were annotated for the NCBI non-redundant protein sequences (Nr, NCBI non-redundant nucleotide sequences (Nt, a manually-annotated and reviewed protein sequence database (Swiss-Prot, Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG databases. Based on the Nr annotation results, we manually identified 79 unigenes encoding cytochrome P450 monooxygenases (P450s, 36 unigenes encoding carboxylesterases (CarEs and 36 unigenes encoding glutathione S-transferases (GSTs in S. shirakii. Core RNAi components relevant to miroRNA, siRNA and piRNA pathways, including Pasha, Loquacious, Argonaute-1, Argonaute-2, Argonaute-3, Zucchini, Aubergine, enhanced RNAi-1 and Piwi, were expressed in S. shirakii. We also identified five unigenes that were homologous to the Sid-1 gene. In addition, the analysis of differential gene expressions revealed that a total of 19,764 unigenes were up-regulated and 4185 unigenes were down-regulated in larvae. In total, we predicted 7504 simple sequence repeats (SSRs from 74,657 unigenes. Conclusions: The comprehensive de novo transcriptomic data of S. shirakii will offer a series of valuable molecular resources for better studying insecticide resistance, RNAi and molecular marker discovery in the transcriptome.

Analysis of SNP rs16754 of WT1 gene in a series of de novo acute myeloid leukemia patients.

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Luna, Irene; Such, Esperanza; Cervera, Jose; Barragán, Eva; Jiménez-Velasco, Antonio; Dolz, Sandra; Ibáñez, Mariam; Gómez-Seguí, Inés; López-Pavía, María; Llop, Marta; Fuster, Óscar; Oltra, Silvestre; Moscardó, Federico; Martínez-Cuadrón, David; Senent, M Leonor; Gascón, Adriana; Montesinos, Pau; Martín, Guillermo; Bolufer, Pascual; Sanz, Miguel A

2012-12-01

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been previously described as a possible prognostic marker in normal karyotype acute myeloid leukemia (AML) patients. Nevertheless, the findings in this field are not always reproducible in different series. One hundred and seventy-five adult de novo AML patients were screened with two different methods for the detection of SNP rs16754: high-resolution melting (HRM) and FRET hybridization probes. Direct sequencing was used to validate both techniques. The SNP was detected in 52 out of 175 patients (30 %), both by HRM and hybridization probes. Direct sequencing confirmed that every positive sample in the screening methods had a variation in the DNA sequence. Patients with the wild-type genotype (WT1(AA)) for the SNP rs16754 were significantly younger than those with the heterozygous WT1(AG) genotype. No other difference was observed for baseline characteristic or outcome between patients with or without the SNP. Both techniques are equally reliable and reproducible as screening methods for the detection of the SNP rs16754, allowing for the selection of those samples that will need to be sequenced. We were unable to confirm the suggested favorable outcome of SNP rs16754 in de novo AML.

Embargos de declaração no processo eleitoral: peculiaridades e breve análise ao projeto de 'novo' código de processo civil

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Rodrigo Reis Mazzei

2013-11-01

Full Text Available Este artigo analisa a regulamentação dos embargos de declaração no seio do processo eleitoral, bem como a interpretação que tem sido dada pelos Tribunais Superiores. Aborda questões essenciais dos embargos de declaração, como prazo, natureza jurídica, hipóteses de cabimento e efeito suspensivo, muitas das quais objeto de discussão na doutrina e jurisprudência devido, sobretudo, à diversificação e variedade das normas que tratam do assunto (Código Eleitoral, regimentos internos dos Tribunais e Código de Processo Civil e Código de Processo Penal – aplicados subsidiariamente, além da necessidade de uma interpretação voltada à natureza constitucional da espécie recursal. Observa as propostas do Projeto do Novo CPC, em trâmite legislativo, para a regulamentação dos embargos de declaração e os impactos que esse novo texto trará ao processo eleitoral, pontuando possíveis caminhos para a conciliação entre o “novo” processo civil e o ordenamento eleitoral.

De novo transcriptome assembly of two different peach cultivars grown in Korea

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Yeonhwa Jo

2015-12-01

Full Text Available Peach (Prunus persica is one of the most popular stone fruits worldwide. Next generation sequencing (NGS has facilitated genome and transcriptome analyses of several stone fruit trees. In this study, we conducted de novo transcriptome analyses of two peach cultivars grown in Korea. Leaves of two cultivars, referred to as Jangtaek and Mibaek, were harvested and used for library preparation. The two prepared libraries were paired-end sequenced by the HiSeq2000 system. We obtained 8.14 GB and 9.62 GB sequence data from Jangtaek and Mibaek (NCBI accession numbers: SRS1056585 and SRS1056587, respectively. The Trinity program was used to assemble two transcriptomes de novo, resulting in 110,477 (Jangtaek and 136,196 (Mibaek transcripts. TransDecoder identified possible coding regions in assembled transcripts. The identified proteins were subjected to BLASTP search against NCBI's non-redundant database for functional annotation. This study provides transcriptome data for two peach cultivars, which might be useful for genetic marker development and comparative transcriptome analyses.

Adopting De Novo Programming Approach on IC Design Service Firms Resources Integration

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James K. C. Chen

2014-01-01

Full Text Available The semiconductor industry has very important position in computer industry, ICT field, and new electronic technology developing. The IC design service is one of key factor of semiconductor industry development. There are more than 365 IC design service firms have been established around Hsinchu Science Park in Taiwan. Building an efficient planning model for IC design service firm resources integrating is very interest issue. This study aims to construct a planning model for IC design service firm implementation resources integration. This study uses the De Novo programming as an approach of criteria alternative to achieve optimal resource allocation on IC design firm. Results show the IC design service firm should conduct open innovation concept and utilizes design outsourcing obtains cost down and enhance IC design service business performance. This plan model of De Novo programming is not only for IC design service firm and also can apply to the other industrial implementation strategic alliance/integrating resource. This plan model is a universal model for the others industries field.

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

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O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

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Idowu, Michael O; Chhatrala, Ravi; Siddiqui, M Bilal; Driscoll, Carolyn; Stravitz, R Todd; Sanyal, Arun J; Bhati, Chandra; Sargeant, Carol; Luketic, Velimir A; Sterling, Richard K; Contos, Melissa; Matherly, Scott; Puri, Puneet; Siddiqui, M Shadab

2015-11-01

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. © 2015 American Association for the Study of Liver Diseases.

Damaging de novo mutations diminish motor skills in children on the autism spectrum.

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Buja, Andreas; Volfovsky, Natalia; Krieger, Abba M; Lord, Catherine; Lash, Alex E; Wigler, Michael; Iossifov, Ivan

2018-02-20

In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills). Copyright © 2018 the Author(s). Published by PNAS.

Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

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Desai Mina

2011-05-01

Full Text Available Abstract Background Small for gestational age (SGA leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR, catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1 and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1 and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

De novo microdeletion of BCL11A is associated with severe speech sound disorder.

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Peter, Beate; Matsushita, Mark; Oda, Kaori; Raskind, Wendy

2014-08-01

In 10 cases of 2p15p16.1 microdeletions reported worldwide to date, shared phenotypes included growth retardation, craniofacial and skeletal dysmorphic traits, internal organ defects, intellectual disability, nonverbal or low verbal status, abnormal muscle tone, and gross motor delays. The size of the deletions ranged from 0.3 to 5.7 Mb, where the smallest deletion involved the BCL11A, PAPOLG, and REL genes. Here we report on an 11-year-old male with a heterozygous de novo 0.2 Mb deletion containing a single gene, BCL11A, and a phenotype characterized by childhood apraxia of speech and dysarthria in the presence of general oral and gross motor dyspraxia and hypotonia as well as expressive language and mild intellectual delays. BCL11A is situated within the dyslexia susceptibility candidate region 3 (DYX3) candidate region on chromosome 2. The present case is the first to involve a single gene within the microdeletion region and a phenotype restricted to a subset of the traits observed in other cases with more extensive deletions. © 2014 Wiley Periodicals, Inc.

De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae

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Koopman Frank

2012-12-01

Full Text Available Abstract Background Flavonoids comprise a large family of secondary plant metabolic intermediates that exhibit a wide variety of antioxidant and human health-related properties. Plant production of flavonoids is limited by the low productivity and the complexity of the recovered flavonoids. Thus to overcome these limitations, metabolic engineering of specific pathway in microbial systems have been envisaged to produce high quantity of a single molecules. Result Saccharomyces cerevisiae was engineered to produce the key intermediate flavonoid, naringenin, solely from glucose. For this, specific naringenin biosynthesis genes from Arabidopsis thaliana were selected by comparative expression profiling and introduced in S. cerevisiae. The sole expression of these A. thaliana genes yielded low extracellular naringenin concentrations ( Conclusion The results reported in this study demonstrate that S. cerevisiae is capable of de novo production of naringenin by coexpressing the naringenin production genes from A. thaliana and optimization of the flux towards the naringenin pathway. The engineered yeast naringenin production host provides a metabolic chassis for production of a wide range of flavonoids and exploration of their biological functions.

Transcriptional regulator-mediated activation of adaptation genes triggers CRISPR de novo spacer acquisition

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Liu, Tao; Li, Yingjun; Wang, Xiaodi

2015-01-01

Acquisition of de novo spacer sequences confers CRISPR-Cas with a memory to defend against invading genetic elements. However, the mechanism of regulation of CRISPR spacer acquisition remains unknown. Here we examine the transcriptional regulation of the conserved spacer acquisition genes in Type I......, it was demonstrated that the transcription level of csa1, cas1, cas2 and cas4 was significantly enhanced in a csa3a-overexpression strain and, moreover, the Csa1 and Cas1 protein levels were increased in this strain. Furthermore, we demonstrated the hyperactive uptake of unique spacers within both CRISPR loci...... in the presence of the csa3a overexpression vector. The spacer acquisition process is dependent on the CCN PAM sequence and protospacer selection is random and non-directional. These results suggested a regulation mechanism of CRISPR spacer acquisition where a single transcriptional regulator senses the presence...

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

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Zarrei, Mehdi; Fehlings, Darcy L; Mawjee, Karizma; Switzer, Lauren; Thiruvahindrapuram, Bhooma; Walker, Susan; Merico, Daniele; Casallo, Guillermo; Uddin, Mohammed; MacDonald, Jeffrey R; Gazzellone, Matthew J; Higginbotham, Edward J; Campbell, Craig; deVeber, Gabrielle; Frid, Pam; Gorter, Jan Willem; Hunt, Carolyn; Kawamura, Anne; Kim, Marie; McCormick, Anna; Mesterman, Ronit; Samdup, Dawa; Marshall, Christian R; Stavropoulos, Dimitri J; Wintle, Richard F; Scherer, Stephen W

2018-02-01

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

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Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

2013-12-01

De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

Robust de novo pathway enrichment with KeyPathwayMiner 5

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Alcaraz, Nicolas; List, Markus; Dissing-Hansen, Martin

2016-01-01

Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks tha...

Sequencing and De Novo Transcriptome Assembly of Brachypodium sylvaticum (Poaceae

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Samuel E. Fox

2013-03-01

Full Text Available Premise of the study: We report the de novo assembly and characterization of the transcriptomes of Brachypodium sylvaticum (slender false-brome accessions from native populations of Spain and Greece, and an invasive population west of Corvallis, Oregon, USA. Methods and Results: More than 350 million sequence reads from the mRNA libraries prepared from three B. sylvaticum genotypes were assembled into 120,091 (Corvallis, 104,950 (Spain, and 177,682 (Greece transcript contigs. In comparison with the B. distachyon Bd21 reference genome and GenBank protein sequences, we estimate >90% exome coverage for B. sylvaticum. The transcripts were assigned Gene Ontology and InterPro annotations. Brachypodium sylvaticum sequence reads aligned against the Bd21 genome revealed 394,654 single-nucleotide polymorphisms (SNPs and >20,000 simple sequence repeat (SSR DNA sites. Conclusions: To our knowledge, this is the first report of transcriptome sequencing of invasive plant species with a closely related sequenced reference genome. The sequences and identified SNP variant and SSR sites will provide tools for developing novel genetic markers for use in genotyping and characterization of invasive behavior of B. sylvaticum.

Identification of novel resistance mechanisms to NAMPT inhibition via the de novo NAD+ biosynthesis pathway and NAMPT mutation.

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Guo, Jun; Lam, Lloyd T; Longenecker, Kenton L; Bui, Mai H; Idler, Kenneth B; Glaser, Keith B; Wilsbacher, Julie L; Tse, Chris; Pappano, William N; Huang, Tzu-Hsuan

2017-09-23

Cancer cells have an unusually high requirement for the central and intermediary metabolite nicotinamide adenine dinucleotide (NAD + ), and NAD + depletion ultimately results in cell death. The rate limiting step within the NAD + salvage pathway required for converting nicotinamide to NAD + is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an anti-cancer strategy, and several highly selective small molecule inhibitors have been found to potently inhibit NAMPT in cancer cells, resulting in NAD + depletion and cytotoxicity. To identify mechanisms that could cause resistance to NAMPT inhibitor treatment, we generated a human fibrosarcoma cell line refractory to the highly potent and selective NAMPT small molecule inhibitor, GMX1778. We uncovered novel and unexpected mechanisms of resistance including significantly increased expression of quinolinate phosphoribosyl transferase (QPRT), a key enzyme in the de novo NAD + synthesis pathway. Additionally, exome sequencing of the NAMPT gene in the resistant cells identified a single heterozygous point mutation that was not present in the parental cell line. The combination of upregulation of the NAD + de novo synthesis pathway through QPRT over-expression and NAMPT mutation confers resistance to GMX1778, but the cells are only partially resistant to next-generation NAMPT inhibitors. The resistance mechanisms uncovered herein provide a potential avenue to continue exploration of next generation NAMPT inhibitors to treat neoplasms in the clinic. Copyright © 2017 Elsevier Inc. All rights reserved.

Perfil epidemiológico do trauma ocular penetrante antes e após o novo código de trânsito

OpenAIRE

Silber,Paulo Caldas; Souza,Luciene Barbosa de; Tongu,Maira Tiyomi Sacata

2002-01-01

Objetivo: Comparar o perfil epidemiológico dos pacientes com trauma ocular penetrante (TOP) antes e após a regulamentação do novo código de trânsito. Métodos: Estudo retrospectivo de 253 pacientes com TOP examinados na Seção de Trauma Ocular (UNIFESP) de janeiro de 1997 a abril de 1999. Os pacientes foram divididos em dois grupos: Grupo I, pacientes com trauma ocular antes da implantação do novo código; Grupo II, história de trauma após sua implantação. Os pacientes foram avaliados em relação...

De novo transcriptome assembly of the mycoheterotrophic plant Monotropa hypopitys

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Alexey V. Beletsky

2017-03-01

Full Text Available Monotropa hypopitys (pinesap is a non-photosynthetic obligately mycoheterotrophic plant of the family Ericaceae. It obtains the carbon and other nutrients from the roots of surrounding autotrophic trees through the associated mycorrhizal fungi. In order to understand the evolutionary changes in the plant genome associated with transition to a heterotrophic lifestyle, we performed de novo transcriptomic analysis of M. hypopitys using next-generation sequencing. We obtained the RNA-Seq data from flowers, flower bracts and roots with haustoria using Illumina HiSeq2500 platform. The raw data obtained in this study can be available in NCBI SRA database with accession number of SRP069226. A total of 10.3 GB raw sequence data were obtained, corresponding to 103,357,809 raw reads. A total of 103,025,683 reads were filtered after removing low-quality reads and trimming the adapter sequences. The Trinity program was used to de novo assemble 98,349 unigens with an N50 of 1342 bp. Using the TransDecoder program, we predicted 43,505 putative proteins. 38,416 unigenes were annotated in the Swiss-Prot protein sequence database using BLASTX. The obtained transcriptomic data will be useful for further studies of the evolution of plant genomes upon transition to a non-photosynthetic lifestyle and the loss of photosynthesis-related functions.

Inflammatory bowel disease after liver transplantation : Risk factors for recurrence and De novo disease

NARCIS (Netherlands)

Verdonka, RC; Dijkstra, G; Haagsma, EB; Shostrom, VK; Van den Berg, AP; Kleibeuker, JH

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver

Blooming Artifact Reduction in Coronary Artery Calcification by A New De-blooming Algorithm: Initial Study.

Science.gov (United States)

Li, Ping; Xu, Lei; Yang, Lin; Wang, Rui; Hsieh, Jiang; Sun, Zhonghua; Fan, Zhanming; Leipsic, Jonathon A

2018-05-02

The aim of this study was to investigate the use of de-blooming algorithm in coronary CT angiography (CCTA) for optimal evaluation of calcified plaques. Calcified plaques were simulated on a coronary vessel phantom and a cardiac motion phantom. Two convolution kernels, standard (STND) and high-definition standard (HD STND), were used for imaging reconstruction. A dedicated de-blooming algorithm was used for imaging processing. We found a smaller bias towards measurement of stenosis using the de-blooming algorithm (STND: bias 24.6% vs 15.0%, range 10.2% to 39.0% vs 4.0% to 25.9%; HD STND: bias 17.9% vs 11.0%, range 8.9% to 30.6% vs 0.5% to 21.5%). With use of de-blooming algorithm, specificity for diagnosing significant stenosis increased from 45.8% to 75.0% (STND), from 62.5% to 83.3% (HD STND); while positive predictive value (PPV) increased from 69.8% to 83.3% (STND), from 76.9% to 88.2% (HD STND). In the patient group, reduction in calcification volume was 48.1 ± 10.3%, reduction in coronary diameter stenosis over calcified plaque was 52.4 ± 24.2%. Our results suggest that the novel de-blooming algorithm could effectively decrease the blooming artifacts caused by coronary calcified plaques, and consequently improve diagnostic accuracy of CCTA in assessing coronary stenosis.

Políticas de Internacionalização das Vanguardas argentinas: Novos modelos institucionais na década de 1960

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Luiza Mader Paladino

2016-12-01

Full Text Available Este artigo procura refletir sobre a relação entre o desenvolvimento das vanguardas artísticas argentinas, ao longo da década de 1960, e a urgência de um novo modelo institucional. O Instituto Di Tella, entidade que protagonizou esse circuito modernizador, se amparou em uma nova modalidade de mecenato cultural privado, ligado aos setores da burguesia industrial, e disposto a apoiar o surgimento de novas vanguardas. O foco deste trabalho se dará nos modos pelos quais esta instituição promoveu e consagrou essas novas vanguardas, sobretudo as advindas da Pop Art, por meio da análise de exposições e premiações que fizeram parte de uma ampla agenda de internacionalização da arte local. Para melhor compreender essas políticas de internacionalização, pretende-se avaliar quais foram os processos de seleção, a composição dos jurados, a legitimação de artistas e dos novos movimentos artísticos desse recente circuito. Ou seja, quem foram esses artistas e por meio de quais linguagens era possível alcançar a internacionalização da arte argentina. A metodologia utilizada para este estudo baseia-se na intersecção entre a pesquisa bibliográfica e a análise de obras com o levantamento de diversos documentos primários do Arquivo do Instituto Torcuato Di Tella, de Buenos Aires.

Aneurismas y seudoaneurismas de injertos venosos coronarios Aneurysms and pseudo aneurysms from coronary venous grafts

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Sergio Franco

2005-04-01

Full Text Available Los aneurismas y seudoaneurismas de injertos de vena safena aortocoronarios, son una complicación inusual de la cirugía de revascularización miocárdica. En este reporte se presenta el caso de un paciente de género masculino de 61 años de edad, quien sufrió un infarto del miocardio de la pared inferior 14 años atrás. La angiografía coronaria mostró enfermedad severa de dos vasos. Se realizó anastomosis de la arteria mamaria interna izquierda, al tercio medio de la descendente anterior e injerto de vena safena al tercio distal de la arteria coronaria derecha. En marzo de 2003, consultó por dolor anginoso. La radiografía de tórax reveló una masa paracardiaca derecha. La arteriografía coronaria mostró aneurisma del puente venoso a la arteria coronaria derecha. Durante la evolución presentó hemoptisis masiva; se hizo cirugía y se halló fístula de aneurisma de puente venoso coronario al lóbulo medio del pulmón derecho. En este artículo se hace una revisión de la etiología, los hallazgos clínicos, la metodología diagnóstica y el tratamiento actual de esta entidad. Hasta la fecha de esta publicación se reportan aproximadamente 60 casos en la literatura inglesa.Aorto-coronary aneurysms/pseudo aneurysms from saphenous vein grafts are an unusual complication of myocardial revascularization surgery. We report the case of a 61 years old male patient who had suffered an inferior wall myocardial infarction 14 years before. Coronary angiography showed severe two-vessel disease. Anastomosis of the left internal mammary artery to the mid third left anterior descendant artery and saphenous vein grafting to the distal third of the right coronary artery, were performed. In March 2003 he complains of anginous pain. Chest X ray showed a right paracardiac mass. Coronary arteriography revealed an aneurysm of the venous bypass graft to the right coronary artery. During the evolution, the patient presents massive hemoptysis, requiring

Os motivos das relações entre orientação para mercado, orientação para aprendizagem e sucesso de novos produtos

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Mauren do Couto Soares

2016-04-01

Full Text Available O objetivo deste trabalho é identificar os motivos das relações entre os construtos de orientação para mercado, orientação para aprendizagem e sucesso de novos produtos. Neste sentido, foram coletadas 32 entrevistas com executivos de empresas de setores representativos da economia brasileira. Os principais resultados indicam que: (1 grande parte dos motivos encontrados nas entrevistas corrobora as evidências levantadas na literatura; (2 algumas variáveis podem moderar as relações entre orientação para mercado, orientação para aprendizagem e sucesso de novos produtos, entre elas a motivação, a burocracia e os recursos humanos; e, (3 empresas que integram os construtos de orientação para mercado, orientação para aprendizagem e sucesso de novos produtos podem potencializar sua performance, facilitando a obtenção de uma vantagem competitiva sustentável.

Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

Science.gov (United States)

de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

2018-04-01

Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

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Lorf Thomas

2010-04-01

Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

The limits of de novo DNA motif discovery.

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David Simcha

Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

Wound complications and surgical events in de novo heart transplant patients treated with everolimus

DEFF Research Database (Denmark)

Rashidi, Mitra; Esmaily, Sorosh; Fiane, Arnt E

2016-01-01

OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin...

A De novo Mutation in Dystrophin Causing Muscular Dystrophy in a Female Patient

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Hao Yu

2017-01-01

Conclusions: We identified two novel de novo mutations of DMD gene in two Chinese pedigrees, one of which caused a female patient with muscular dystrophy. The mutational analysis is important for DMD patients and carriers in the absence of a family history. The NGS can help detect the mutations in MLPA-negative patients.

Uncovering Clinical Features of De Novo Philadelphia Positive Myelodysplasia.

Science.gov (United States)

Armas, Aristides; Chen, Chen; Mims, Martha; Rivero, Gustavo

2017-01-01

Myelodysplastic syndrome (MDS) is cytogenetically heterogeneous and retains variable risk for acute myeloid leukemia transformation. Though not yet fully understood, there is an association between genetic abnormalities and defects in gene expression. The functional role for infrequent cytogenetic alteration remains unclear. An uncommon chromosomic abnormality is the presence of the Philadelphia (Ph) chromosome. Here, we report a patient with Ph+ MDS treated with low dose Dasatinib who achieved hematologic response for 7 months. In addition, we also examined the English literature on all de novo Ph + MDS cases between 1996 and 2015 to gain insight into clinical features and outcome.

A influência da capacidade de aprendizado, da criatividade organizacional, da orientação empreendedora internacional, da capacidade tecnológica e da capacidade de reconfiguração na habilidade em desenvolvimento de novos produtos

OpenAIRE

Panizzon, Mateus

2016-01-01

Em um contexto de globalização, com a intensificação do desenvolvimento econômico baseado em conhecimento, inovação e criatividade como fontes de valor agregado, empresas buscam continuamente vantagem competitiva sustentável em ambientes de mudança e turbulência. Deste modo, a agenda de pesquisa teórica nos campos das Capacidades Dinâmicas Baseadas em Conhecimento, Criatividade Organizacional, Orientação Empreendedora Internacional e Desenvolvimento de Novos Produtos motiva novos estudos e re...

A Case of De Novo Anterior Condylar Dural Arteriovenous Fistula Long after Curative Transvenous Embolization of Contralateral Anterior Condylar Arteriovenous Fistula

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Shinya Hagiwara

2016-01-01

Full Text Available We report on a 55-year-old man who developed a de novo DAVF in left ACC 5 years after curative transvenous embolization for DAVF in right ACC. Angiography revealed that the de novo lesion demonstrated more aggressive arteriovenous shunt flow than the initial lesion. Successful transvenous embolization was performed for also the second lesion. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence.

Novos paradigmas literários

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Denise Azevedo Duarte Guimarães

2005-12-01

Full Text Available O artigo estuda a emergência de novos paradigmas literários, procurando refletir acerca das textualidades contemporâneas. Focaliza os hipertextos informatizados e a poesia multimídia, com o intuito de desvendar como estão sendo criados novos procedimentos expressivos e em que medida eles podem ser identificados com reflexões teóricas anteriores acerca do texto literário impresso. Remete a questões ligadas à leitura dos diferentes tipos de signos e aos modos como eles se integram para a constituição dessas novíssimas linguagens híbridas em novos suportes.El artículo estudia la emergencia de nuevos paradigmas literarios, procurando reflejar acerca de las textualidades contemporáneas. Enfoca los hipertextos informatizados y la poesía multimedia, intentando desvendar cómo están siendo creados nuevos procedimientos expresivos y en qué medida ellos pueden ser identificados a reflexiones teóricas anteriores acerca del texto literario impreso. Remite a cuestiones ligadas a la lectura de los diferentes tipos de signos y a los modos cómo ellos se interaccionan para la constitución de los novísimos lenguajes híbridos en nuevos supuestos.This article investigates the emergence of new literary paradigms as it tries to understand new contemporary textualities. It analyses some hypertexts and multimedia poetry trying to trace how new expressive procedures are being created. How can these new languages be identified and what are their relations to previous theories which dealt with the literary printed text? This study approaches questions linked to the reading of different types of signs and the modes they function towards the fabrication of these new hybrid languages.

Primary intraosseous squamous cell carcinoma of the mandible arising de novo.

Science.gov (United States)

Shamim, Thorakkal

2009-07-01

Primary intraosseous squamous cell carcinoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th to 7th decades of life. The tumour is characterized by progressive swelling of the jaw, pain and loosening of teeth. Microscopically, the lesion is showing foci of keratinising cells separated by collagenous connective tissue stroma. A case of primary intraosseous squamous cell carcinoma of mandible arising de novo in a 40-year-old man is reported.

Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

Science.gov (United States)

Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

2016-12-01

: Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

Single lesion as an indicator to monitor the leprosy trend to elimination in hyperendemic areas Lesão única como indicador de monitoramento de tendência de eliminação da hanseníase em áreas hiperendêmicas

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Eliane Ignotti

2007-09-01

Full Text Available INTRODUCTION: Prevalence and detection rates of leprosy are not sufficient to show the real magnitude of changes in epidemiological patterns. OBJECTIVES: Evaluate the feasibility and usefulness of the proportion of new leprosy patients with a single skin lesion (SSL as a potential indicator of the elimination of leprosy. METHODS: We conducted a retrospective study based on secondary data analyzing newly reported cases of leprosy between 1997 and 2002, in the city of Palmas, Tocantins, Brazil. Patients with a single lesion were compared to remaining patients, and the odds ratio was used as measure of association. RESULTS: Out of the 1,303 new cases of leprosy, 481 (36.9% had a SSL. An increasing time-trend was observed in the proportion of new cases detected with a single lesion, which grew from 20.3% in 1999 to 49.1% in 2002 (linear trend pINTRODUÇÃO: As taxas de detecção e prevalência de hanseníase não são suficientes para mostrar a real magnitude de mudanças nos padrões epidemiológicos da doença. OBJETIVOS: Avaliar a aplicabilidade e utilidade da medida de proporção de casos de hanseníase com lesão única de pele como potencial indicador de avaliação do progresso da eliminação da hanseníase em áreas hiperendêmicas. METODOLOGIA: Estudo retrospectivo baseado na análise de dados secundários de casos novos de hanseníase notificados entre 1997 e 2002 na cidade de Palmas, estado de Tocantins, Brasil. Os registros de pacientes com lesão única foram comparados àqueles registrados com mais de uma lesão. Odds ratio foi utilizado como medida de associação. RESULTADOS: De um total de 1.303 casos novos de hanseníase notificados, 481 (36,9% apresentavam lesão única de pele. Verificou-se tendência de incremento na proporção de casos de casos novos diagnosticados com lesão única variando de 20,3% em 1999 para 49,1% em 2002 (p < 0,001, simultaneamente à redução do registro de número de casos novos após 1999. Maior

Comparison of immediate results and follow-up of patients with single-vessel and multivessel coronary artery disease younger than 50 years of age undergoing coronary stent implantation

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Anello Alexandre L.

2003-01-01

Full Text Available OBJECTIVE: To assess the in-hospital results and clinical follow-up of young patients (< 50 years with multivessel coronary artery disease undergoing stent implantation in native coronary arteries and to compare their results with those of patients with single-vessel coronary artery disease. METHODS: We retrospectively studied 462 patients undergoing coronary stent implantation. Patients were divided into 2 groups: group I (G-I - 388 (84% patients with single-vessel coronary artery disease; and group II (G-II - 74 (16% patients with multivessel coronary artery disease. RESULTS: The mean age of the patients was 45±4.9 years, and the clinical findings at presentation and demographic data were similar in both groups. The rate of clinical success was 95% in G-I and 95.8% in G-II (P=0.96, with no difference in regard to in-hospital evolution between the groups. Death, acute myocardial infarction, and the need for myocardial revascularization during clinical follow-up occurred in 10.1% and 11.2% (P=0.92 in G-I and G-II, respectively. By the end of 24 months, the actuarial analysis showed an event-free survival of 84.6 % in G-I and 81.1% in G-II (P=0.57. CONCLUSION: Percutaneous treatment with coronary stent implantation in young patients with multivessel disease may be safe with a high rate of clinical success, a low incidence of in-hospital complications, and a favorable evolution in clinical follow-up.

Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

DEFF Research Database (Denmark)

Obsen, Thomas; Faergeman, Nils J; Chung, Soonkyu

2012-01-01

7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA......]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10...... is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA....

Optimizing and benchmarking de novo transcriptome sequencing: from library preparation to assembly evaluation.

Science.gov (United States)

Hara, Yuichiro; Tatsumi, Kaori; Yoshida, Michio; Kajikawa, Eriko; Kiyonari, Hiroshi; Kuraku, Shigehiro

2015-11-18

RNA-seq enables gene expression profiling in selected spatiotemporal windows and yields massive sequence information with relatively low cost and time investment, even for non-model species. However, there remains a large room for optimizing its workflow, in order to take full advantage of continuously developing sequencing capacity. Transcriptome sequencing for three embryonic stages of Madagascar ground gecko (Paroedura picta) was performed with the Illumina platform. The output reads were assembled de novo for reconstructing transcript sequences. In order to evaluate the completeness of transcriptome assemblies, we prepared a reference gene set consisting of vertebrate one-to-one orthologs. To take advantage of increased read length of >150 nt, we demonstrated shortened RNA fragmentation time, which resulted in a dramatic shift of insert size distribution. To evaluate products of multiple de novo assembly runs incorporating reads with different RNA sources, read lengths, and insert sizes, we introduce a new reference gene set, core vertebrate genes (CVG), consisting of 233 genes that are shared as one-to-one orthologs by all vertebrate genomes examined (29 species)., The completeness assessment performed by the computational pipelines CEGMA and BUSCO referring to CVG, demonstrated higher accuracy and resolution than with the gene set previously established for this purpose. As a result of the assessment with CVG, we have derived the most comprehensive transcript sequence set of the Madagascar ground gecko by means of assembling individual libraries followed by clustering the assembled sequences based on their overall similarities. Our results provide several insights into optimizing de novo RNA-seq workflow, including the coordination between library insert size and read length, which manifested in improved connectivity of assemblies. The approach and assembly assessment with CVG demonstrated here would be applicable to transcriptome analysis of other species as

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

NARCIS (Netherlands)

de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van 't Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C

2016-01-01

BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

DEFF Research Database (Denmark)

de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah

2016-01-01

BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellect...

Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.

Science.gov (United States)

Siciliano, Mattia; De Micco, Rosa; Trojano, Luigi; De Stefano, Manuela; Baiano, Chiara; Passaniti, Carla; De Mase, Antonio; Russo, Antonio; Tedeschi, Gioacchino; Tessitore, Alessandro

2017-08-01

The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages. Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II. Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II. In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI. Copyright © 2017 Elsevier Ltd. All rights reserved.

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Science.gov (United States)

Heinzen, Erin L.; Swoboda, Kathryn J.; Hitomi, Yuki; Gurrieri, Fiorella; Nicole, Sophie; de Vries, Boukje; Tiziano, F. Danilo; Fontaine, Bertrand; Walley, Nicole M.; Heavin, Sinéad; Panagiotakaki, Eleni; Fiori, Stefania; Abiusi, Emanuela; Di Pietro, Lorena; Sweney, Matthew T.; Newcomb, Tara M.; Viollet, Louis; Huff, Chad; Jorde, Lynn B.; Reyna, Sandra P.; Murphy, Kelley J.; Shianna, Kevin V.; Gumbs, Curtis E.; Little, Latasha; Silver, Kenneth; Ptác̆ek, Louis J.; Haan, Joost; Ferrari, Michel D.; Bye, Ann M.; Herkes, Geoffrey K.; Whitelaw, Charlotte M.; Webb, David; Lynch, Bryan J.; Uldall, Peter; King, Mary D.; Scheffer, Ingrid E.; Neri, Giovanni; Arzimanoglou, Alexis; van den Maagdenberg, Arn M.J.M.; Sisodiya, Sanjay M.; Mikati, Mohamad A.; Goldstein, David B.; Nicole, Sophie; Gurrieri, Fiorella; Neri, Giovanni; de Vries, Boukje; Koelewijn, Stephany; Kamphorst, Jessica; Geilenkirchen, Marije; Pelzer, Nadine; Laan, Laura; Haan, Joost; Ferrari, Michel; van den Maagdenberg, Arn; Zucca, Claudio; Bassi, Maria Teresa; Franchini, Filippo; Vavassori, Rosaria; Giannotta, Melania; Gobbi, Giuseppe; Granata, Tiziana; Nardocci, Nardo; De Grandis, Elisa; Veneselli, Edvige; Stagnaro, Michela; Gurrieri, Fiorella; Neri, Giovanni; Vigevano, Federico; Panagiotakaki, Eleni; Oechsler, Claudia; Arzimanoglou, Alexis; Nicole, Sophie; Giannotta, Melania; Gobbi, Giuseppe; Ninan, Miriam; Neville, Brian; Ebinger, Friedrich; Fons, Carmen; Campistol, Jaume; Kemlink, David; Nevsimalova, Sona; Laan, Laura; Peeters-Scholte, Cacha; van den Maagdenberg, Arn; Casaer, Paul; Casari, Giorgio; Sange, Guenter; Spiel, Georg; Boneschi, Filippo Martinelli; Zucca, Claudio; Bassi, Maria Teresa; Schyns, Tsveta; Crawley, Francis; Poncelin, Dominique; Vavassori, Rosaria

2012-01-01

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations. AHC is usually a sporadic disorder with unknown etiology. Using exome sequencing of seven patients with AHC, and their unaffected parents, we identified de novo nonsynonymous mutations in ATP1A3 in all seven AHC patients. Subsequent sequence analysis of ATP1A3 in 98 additional patients revealed that 78% of AHC cases have a likely causal ATP1A3 mutation, including one inherited mutation in a familial case of AHC. Remarkably, six ATP1A3 mutations explain the majority of patients, including one observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset-dystonia-parkinsonism, AHC-causing mutations revealed consistent reductions in ATPase activity without effects on protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC, and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in this gene. PMID:22842232

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

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Atsushi Takata

2018-01-01

Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

Perinatal Autopsy Findings in a Case of De Novo Hypohidrotic Ectodermal Dysplasia.

Science.gov (United States)

Chikkannaiah, Panduranga; Nagaraju, Smitha; Kangle, Rajit; Gosavi, Mansi

2015-01-01

Ectodermal dysplasia are group of inherited disorders involving the developmental defects of ectodermal structures like hair, teeth, nails, sweat glands, and others. X-linked recessive inheritance is most common. Here we describe perinatal autopsy findings in a case of de novo ectodermal dysplasia in a female fetus. To the best of our knowledge, this is the first fetal autopsy description in a case of ectodermal dysplasia.

De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

Science.gov (United States)

Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

2015-01-01

Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

De novo origin of VCY2 from autosome to Y-transposed amplicon.

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Peng-Rong Cao

Full Text Available The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y

Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

International Nuclear Information System (INIS)

Tanaka, K.; Tanaka, H.; Kamada, N.

2003-01-01

It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

Mulheres, saúde e uso de crack: a reprodução do novo racismo na/pela mídia televisiva

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Fernanda dos Santos de Macedo

2015-12-01

Full Text Available A discussão engendrada neste artigo versa sobre as possíveis relações entre os discursos veiculados na mídia televisiva sobre a atenção à saúde, enfocando mulheres que fazem uso de crack e na reprodução do "novo racismo" - expressão empregada no campo dos Estudos Críticos do Discurso. Ainda, observamos as possíveis interlocuções do novo racismo com os discursos relacionados aos direitos sexuais e reprodutivos. Trata-se de um levantamento de documentos de domínio público, que tem como referencial teórico-metodológico os Estudos Críticos do Discurso, assim como os pressupostos da Psicologia Social Crítica em articulação com os Estudos de Gênero. Concluímos que quando o discurso midiático em foco, transmissor da ideologia das elites simbólicas, aborda as mulheres que usam crack na gravidez como um problema social desvinculado do contexto histórico, político e sociocultural, reproduz um novo racismo. Em virtude do caráter de legitimidade dos meios de comunicação de massa, as atitudes racistas são compartilhadas na sociedade, aprofundando-se, assim, as iniquidades sociais e as discriminações de gênero.

Effect of 6-BA on nodal explant bud sproutings of Coffea arabica cv. Mundo Novo Efeito de 6-BA na brotação de gemas de explantes nodais de Coffea arabica cv. Mundo Novo

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Luis Carlos da Silva Ramos

2005-01-01

Full Text Available Coffee plants can be micropropagated by nodal bud sprouting using the 6-benzylaminopurine (6-BA hormone. However, literature reports the use of a wide range of 6-BA, from 0.5 to 88.8 µM L-1. So, this study was performed to narrow that range. Nodal explants of Coffea arabica cv Mundo Novo obtained from in vitro plantlets were inoculated on gelled-MS medium supplemented with different concentrations of 6-BA. Two assays were carried out: in the first one, 6-BA was used at concentrations of 0, 5, 25, 50, and 100 µM L-1, being evaluated at 43 and 123 days. In the second experiment, dosis of 10, 20 and 30 µM L-1, have evaluated at 65 and 100 days. Treatments with 6-BA induced multiple sprouting from the nodal explants, which were best characterized around 100 days after inoculation. The nodal explants grew taller and showed multiple shoots, whereas the effect of 6-BA at 5 to 25 µM L-1 was similar to that with higher concentrations (50 and 100 µM L-1. Nodal explants yielded from 2.9 to 6.0 buds per node, achieving height of 1.3 to 1.5 cm at 5 to 25 µM L-1 of 6-BA, whereas they yielded from 4.3 to 4.9 buds per node but the sprouting grew about 0.8 cm at 50 and 100 µM L-1 of 6-BA. This study indicated that multiple sprouting of lateral buds can be induced by lower concentrations of 6-BA, for example, from 10 to 30 µM L-1, diminishing possible risks of somaclonal variation due to high levels of hormone concentration.O cafeeiro pode ser micropropagado via brotação de gemas laterais, aplicando o regulador de crescimento 6-benzilaminopurina (6-BA. Entretanto, a literatura apresenta ampla variação da dose empregada, desde 0.5 a 88.8 µM L-1. Assim, este estudo visou otimizar doses para explantes nodais do cafeeiro C. arabica cv Mundo Novo. Explantes nodais, obtidos de plântulas cultivadas in vitro, foram inoculados em meio MS geleificado, com adição de diferentes concentrações de 6-BA. Foram feitos dois experimentos: no primeiro, 6-BA foi

Molecular analysis of "de novo" purine biosynthesis in solanaceous species and in Arabidopsis thaliana

DEFF Research Database (Denmark)

van der Graaff, Eric; Hooykaas, Paul; Lein, Wolfgang

2004-01-01

Purine nucleotides are essential components to sustain plant growth and development. In plants they are either synthesized "de novo" during the process of purine biosynthesis or are recycled from purine bases and purine nucleosides throughout the salvage pathway. Comparison between animals...... biosynthesis pathway in plants, and the in planta functional analysis of PRPP (5-phosphoribosyl-1-pyrophoshate) amidotransferase (ATase), catalyzing the first committed step of the "de novo" purine biosynthesis. The cloning of the genes involved in the purine biosynthesis pathway was attained by a screening...... strategy with heterologous cDNA probes and by using S. cerevisiae mutants for complementation. Southern hybridization showed a complex genomic organization for these genes in solanaceous species and their organ- and developmental specific expression was analyzed by Northern hybridization. The specific role...

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

Science.gov (United States)

Boyden, Lynn M; Kam, Chen Y; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G; Sidbury, Robert; Mathes, Erin F; Maguiness, Sheilagh M; Crumrine, Debra A; Williams, Mary L; Hu, Ronghua; Lifton, Richard P; Elias, Peter M; Green, Kathleen J; Choate, Keith A

2016-01-15

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

UTILIZAÇÃO DE PLANTAS ORNAMENTAIS COMO NOVOS INDICADORES NATURAIS ÁCIDO-BASE NO ENSINO DE QUÍMICA

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Valdiléia Teixeira Uchôa

2016-04-01

Full Text Available A química é uma disciplina de caráter teórico-prática, mas vem sendo praticamente repassada na base de teoria, podendo acarretar desinteresse dos alunos. Isso acontece pela falta de estrutura e materiais laboratoriais nas escolas para a realização das práticas. Tal problema pode ser solucionado com a utilização de materiais alternativos para a realização das aulas praticas. A utilização de indicadores naturais ácido-base é uma proposta que vem sendo bastante trabalhada. Os indicadores naturais são substâncias que possuem extratos ricos em antocianinas, apresentando coloração diferente dependendo do meio reacional que sejam inseridas. O objetivo desse estudo foi avaliar a eficácia do extrato aquoso de duas plantas ornamentais a Allamanda cathartica L. e a Codiaeum variegatum (L. A. Juss. como novos indicadores naturais ácido-base, comparando sua potencialidade com extrato da beterraba (Beta vulgaris L e do repolho roxo (Brassica oleracea L. var. capitata L. descritos na literatura. Este estudo começou com a extração do extrato das flores da alamanda-amarela e das folhas do louro variegado, testando em soluções de pH com variação de 1 a 14. Para o teste de estabilidade foram acondicionados 2 amostras de cada extrato: uma a 0 ºC (período de 30 dias e  a 25 ºC (período de 5 e 10 dias. Os resultados obtidos demonstraram uma boa eficácia dos novos indicadores, apresentando uma estabilidade térmica significativa em comparação com os já presentes na literatura, sendo uma alternativa de fácil aquisição e baixo custo para serem usados nas práticas do conteúdo de ácido-base da disciplina química na Educação Básica.

A SA8000 e a responsabilidade social das empresas: a emergência de um novo paradigma?

OpenAIRE

Lopes, Ana Catarina Marques Figueiredo Caetano

2004-01-01

Mestrado em Desenvolvimento e Cooperação Internacional A Responsabilidade Social das Empresas, não é um tema novo. Durante muito tempo foi discutido e interpretado no âmbito do debate sobre as responsabilidades que uma empresa deve assumir para além daquelas que tem perante os seus accionistas, e das impostas por lei. Hoje, observamos a emergência de um novo paradigma assente no reconhecimento que o sector privado não só pode, mas deve, fazer mais para combater a pobreza, preservar o meio ...

Los "intelectuales" y el Estado Novo

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Luís REIS TORGAL

2010-02-01

Full Text Available RESUMEN: El concepto de “intelectual” es difícil de definir y sin duda se debate constantemente. Sin embargo, es importante reflexionar sobre él a fin de comprender su significado y los problemas que implica. Sea como fuere, a un Estado autoritario “moderno” se le supone una única ideología que tiene que difundirse por medio de una propaganda bien organizada, proceso en el que los intelectuales desempeñan un papel significativo. El “Nuevo Estado” de Salazar encaja en esta categoría y sin duda el conocimiento acerca de sus “intelectuales” es fundamental. En este artículo, el objetivo es proporcionar algunos ejemplos interesantes de “intelectuales” o de simples “funcionarios políticos” con inclinación intelectual a fin de indicar el sentido y complejidad de un estudio con una dimensión distinta sobre este asunto. A este fin han sido seleccionadas tres personalidades responsables de la actividad ideológica y cultural de gran relieve en el Estado de Salazar: António Ferro, João Ameal y Costa Brochado. Palabras clave: Estado Novo; Authotitarianism; Salazar, António de Oliveira; Intellectuals; Ferro, António; Brochado, Idalino da Costa; Ameal, João. ABSTRACT: The concept of the “intellectual” is difficult to define and undoubtedly constantly debated. It is nevertheless important to reflect on it in order to understand its meaning and the problems involved with it. Be that as it may, a “modern” authoritarian State presumes a single ideology which has to be diffused by means of well-organised propaganda, in which process “intellectuals” play a significant role. Salazar’s “New State” fits this category and, undoubtedly, knowledge about its “intellectuals” is fundamental. The objective in this article is to provide some interesting examples of “intellectuals” or simple “political functionar- ies” with an intellectual bent so as to indicate the sense and complexity of a study of a

Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction.

Science.gov (United States)

Choi, Ki Hong; Lee, Ga Yeon; Choi, Jin-Oh; Jeon, Eun-Seok; Lee, Hae-Young; Cho, Hyun-Jai; Lee, Sang Eun; Kim, Min-Seok; Kim, Jae-Joong; Hwang, Kyung-Kuk; Chae, Shung Chull; Baek, Sang Hong; Kang, Seok-Min; Choi, Dong-Ju; Yoo, Byung-Su; Kim, Kye Hun; Park, Hyun-Young; Cho, Myeong-Chan; Oh, Byung-Hee

2018-03-01

There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02). HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted

A Presença da Gastronomia Alemã na Hotelaria de Novo Hamburgo, RS

OpenAIRE

mary sandra ashton; Ana Cristina Müller

2013-01-01

Esse estudo tem por objetivo investigar os elementos e características da gastronomia alemã presentes nos serviços hoteleiros de Novo Hamburgo. Tem ênfase na gastronomia, evidenciando e (re) conhecendo os hábitos e costumes alimentares trazidos pela imigração germânica e sua relação com a oferta de alimentos nos hotéis da cidade, como diferencial no quesito turismo cultural. Para tanto, foram utilizados autores reconhe...

Novos instrumentos de financiamento do agronegócio brasileiro e uma análise das alternativas de investimentos para o CDA/WA

OpenAIRE

Gustavo de Souza e Silva

2006-01-01

O instrumento tradicional de financiamento é aquele utilizado pelo Sistema Nacional de Crédito Rural - SNCR e que possui como fonte o orçamento do governo, as exigibilidades bancárias, a poupança verde etc. Os instrumentos não tradicionais podem ser considerados os novos mecanismos com fonte de recursos privados e que pretendem substituir os instrumentos tradicionais no financiamento agropecuário. A Lei n° 11.076, de 30 de dezembro de 2004, oficializou cinco títulos de créditos que deverão se...

Norgal: Extraction and de novo assembly of mitochondrial DNA from whole-genome sequencing data

DEFF Research Database (Denmark)

Al-Nakeeb, Kosai Ali Ahmed; Petersen, Thomas Nordahl; Sicheritz-Pontén, Thomas

2017-01-01

and performing a de novo assembly on a subset of reads that contains these k-mers. The method was applied to WGS data from a panda, brown algae seaweed, butterfly and filamentous fungus. We were able to extract full circular mitochondrial genomes and obtained sequence identities to the reference sequences...

Serial 5-Year Evaluation of Side Branches Jailed by Bioresorbable Vascular Scaffolds Using 3-Dimensional Optical Coherence Tomography: Insights From the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

Science.gov (United States)

Onuma, Yoshinobu; Grundeken, Maik J; Nakatani, Shimpei; Asano, Taku; Sotomi, Yohei; Foin, Nicolas; Ng, Jaryl; Okamura, Takayuki; Wykrzykowska, Joanna J; de Winter, Robbert J; van Geuns, Robert-Jan; Koolen, Jacques; Christiansen, Evald; Whitbourn, Robert; McClean, Dougal; Smits, Pieter; Windecker, Stephan; Ormiston, John A; Serruys, Patrick W

2017-09-01

The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb bioresorbable vascular scaffold struts. We performed 3-dimensional optical coherence tomographic analysis of the ABSORB Cohort B trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) up to 5 years using a novel, validated cut-plane analysis method. We included 29 patients with a total of 85 side branch ostia. From the 12 ostia which could be assessed in true serial fashion, 7 showed a pattern of initial decrease in the ostial area free from struts, followed by an increase in strut-free ostial area toward the end of the 5 years of follow-up. In a repeated-measures analysis with time as fixed variable and ostial area free from struts as dependent variable, we showed a numeric decrease in the estimated ostial area free from struts from 0.75 mm 2 (baseline) to 0.68 mm 2 (first follow-up visit at 6 months or 1 year) and 0.63 mm 2 (second follow-up visit at 2 or 3 years). However, from the second visit to the 5-year follow-up visit, there was a statistically significant increase from 0.63 to 0.89 mm 2 ( P =0.001). Struts overlying an ostium divided the ostium into compartments, and the number of these compartments decreased over time. This study showed that in most cases, the side branch ostial area free from struts initially decreased. However, with full scaffold bioresorption, the ostial area free from scaffold increased between 2 to 3 years and 5 years in the vast majority of patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856. © 2017 American Heart Association, Inc.

Discovery of new antitumoral and antibacterial drugs from brazilian plant extracts using high throughput screening Descoberta de novos fármacos anti-tumorais e anti-bacterianos de extratos vegetais brasileiros através de screening em larga escala

Directory of Open Access Journals (Sweden)

Riad Naim Younes

2007-01-01

Full Text Available Plants have played a significant role in the treatment of cancer and infectious diseases for the last four decades. The discovery and introduction to market of paclitaxel, the vinca alkaloids, etoposide, and many antibacterial drugs support drug discovery programs based on natural products. Natural products have been rediscovered as important tools for drug development despite advances in combinatorial chemistry, due to the complex molecular structures able to interact with mammalian cell targets. The Brazilian flora, the most diverse in the world, has become an interesting spot to prospect for new chemical leads or hits due to its species diversity and associated chemical richness. Screening programs have been established in Brazil as a strategy to identify potentially active substances. High throughput screening techniques allow for the analysis of large numbers of extracts in a relatively short period of time, and can be considered one of the most efficient ways of finding new leads from natural products. An updated review of the current status of the biological screening program is presented and recent results from new antitumoral and antibacterial chemical leads are discussed.Plantas são uma importante fonte de novos protótipos há pelo menos quatro décadas. A descoberta e introdução no mercado de paclitaxel, dos alcalóides da vinca, etoposídeo e muitos agentes antibacterianos têm servido de apoio ao desenvolvimento de programas de descobrimento de novos fármacos baseados em produtos naturais. Produtos naturais foram recentemente redescobertos como importante ferramenta na descoberta de novos fármacos devido às estruturas moleculares complexas capazes de interagir com alvos em células de mamíferos. A flora brasileira, a mais rica do mundo, tornou-se um importante sítio para prospecção de novos protótipos em decorrência da riqueza de espécies vegetais relacionada a uma possível diversidade química. Programas de triagem t

Novos compostos de coordenação heteronucleares de Fe"Ni" e Ga"Ni" como modelos para as fosfatases ácidas púrpuras substituídas

OpenAIRE

Batista, Suzana Cimara

2003-01-01

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química. Novos compostos de coordenação heterobinucleares de FeIIINiII e GaIIINiII como modelos para as fosfatases ácidas púrpuras.

Desenvolvimento de um novo produto cerâmico para pavimentação de passeios e áreas públicas

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Lilian Lima Dias

Full Text Available Resumo Mobilidade e segurança são temas cada vez mais discutidos nos grandes centros urbanos, e as iniciativas nesse universo devem prever soluções práticas e econômicas, que gerem benefícios para os cidadãos. O pavimento, um dos fatores para a qualidade urbana, é a via de acesso indispensável para garantir o direito de ir e vir. Entre as soluções, o pavimento intertravado se destaca como um dos produtos mais recomendados na pavimentação das calçadas e áreas públicas. Em países da Europa e da América Latina a pavimentação com sistemas intertravados de cerâmicas é amplamente utilizada, porém essa prática ainda é pouco observada no Brasil, pela inexistência desse produto no mercado local. Desse modo, o objetivo deste projeto foi o desenvolvimento de pavimentos intertravados de cerâmica visando ao uso em passeios e áreas públicas. Também foram adicionados ao novo produto desenvolvido resíduos queimados oriundos do próprio processo de fabricação, os quais são chamados de cacos ou chamote, para diminuir a quantidade de material a ser descartado no meio ambiente. Após os resultados positivos na caracterização dos produtos, foram criados novos designs para essa tipologia de produtos, os quais foram produzidos em escala laboratorial.

De novo assembly of human genomes with massively parallel short read sequencing

DEFF Research Database (Denmark)

Li, Ruiqiang; Zhu, Hongmei; Ruan, Jue

2010-01-01

genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities...... for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way....

Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

Science.gov (United States)

Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

2015-05-01

The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography

DEFF Research Database (Denmark)

Rochitte, Carlos E; George, Richard T; Chen, Marcus Y

2014-01-01

AIMS: To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed...... emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA...... tomography (SPECT). METHODS AND RESULTS: We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon...

De novo transcriptome assembly of the calanoid copepod Neocalanus flemingeri: A new resource for emergence from diapause.

Science.gov (United States)

Roncalli, Vittoria; Cieslak, Matthew C; Sommer, Stephanie A; Hopcroft, Russell R; Lenz, Petra H

2018-02-01

Copepods, small planktonic crustaceans, are key links between primary producers and upper trophic levels, including many economically important fishes. In the subarctic North Pacific, the life cycle of copepods like Neocalanus flemingeri includes an ontogenetic migration to depth followed by a period of diapause (a type of dormancy) characterized by arrested development and low metabolic activity. The end of diapause is marked by the production of the first brood of eggs. Recent temperature anomalies in the North Pacific have raised concerns about potential negative effects on N. flemingeri. Since diapause is a developmental program, its progress can be tracked using through global gene expression. Thus, a reference transcriptome was developed as a first step towards physiological profiling of diapausing females using high-throughput Illumina sequencing. The de novo transcriptome, the first for this species was designed to investigate the diapause period. RNA-Seq reads were obtained for dormant to reproductive N. flemingeri females. A high quality de novo transcriptome was obtained by first assembling reads from each individual using Trinity software followed by clustering with CAP3 Assembly Program. This assembly consisted of 140,841transcripts (contigs). Bench-marking universal single-copy orthologs analysis identified 85% of core eukaryotic genes, with 79% predicted to be complete. Comparison with other calanoid transcriptomes confirmed its quality and degree of completeness. Trinity assembly of reads originating from multiple individuals led to fragmentation. Thus, the workflow applied here differed from the one recommended by Trinity, but was required to obtain a good assembly. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Melhoramento do cafeeiro: IV - Café Mundo Novo

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A. Carvalho

1952-06-01

Full Text Available Em um conjunto de cafeeiros existentes em Mundo Novo, hoje Urupês, na região Araraquarense do Estado de São Paulo, foram feitas seleções de vários cafeeiros baseando-se no seu aspecto vegetativo, na produção existente na época da seleção e na provável produção do ano seguinte. Estudou-se a origem da plantação inicial desse café, tanto em Urupês como em Jaú, chegando-se à conclusão de que é provavelmente originário desta última localidade. Progênies do café "Mundo Novo", anteriormente conhecido por "Sumatra" e derivado de plantas selecionadas em Urupês e Jaú, acham-se em estudo em seis localidades do Estado : Campinas, Ribeirão Prêto, Pindorama, Mococa, Jaú e Monte Alegre do Sul. No presente trabalho são apenas aproveitados dados referentes à variabilidade morfológica e característicos da produção das progênies dos primeiros cafeeiros selecionados em Urupês e estudados em Campinas, Jaú, Pindorama e Mococa. Em tôdas as localidades, observou-se variação nos caracteres morfológicos das progênies, verificando-se a ocorrência de plantas quase improdutivas. A maioria das progênies, no entanto, se caracteriza por acentuado vigor vegetativo. Foram estudadas as produções totais das progénies e das plantas, no período 1946-1951, notando-se que algumas progénies se salientaram pela elevada produção em tôdas as localidades. Os tipos de sementes "moca", "concha" e "chato" foram determinados em amostras de tôdas as plantas, por um período de três anos, notando-se que a variação ocorrida é da mesma ordem que a encontrada em outros cafeeiros em seleção. Procurou-se eliminar, pela seleção, cafeeiros com elevada produção de frutos sem sementes em uma ou duas lojas, característico êsse que parece ser hereditário. Os resultados obtidos de cruzamento entre os melhores cafeeiros "Mundo Novo" de Campinas e plantas da variedade murta, indicaram que esses cafeeiros são do tipo bourbon. Provavelmente

Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?

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Banović Marko

2010-01-01

Full Text Available Introduction. Acute heart failure (AHF is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. Objective. To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF and to identify differences in blood levels of biomarkers and echocardiography findings. Methods. This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%, and patients with acute worsening of CHF (54.7%. Results. Acute congestion (60% was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1% was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 μmol/l; p<0.05, urea (12.63 vs 7.82 mmol/l; p<0.05, BNP (1440.11 vs 712.24 pg/ml; p<001 and NTproBNP (9097.00 vs 2827.70 pg/ml; p<0.01 on admission, and lower values of M-mode left ventricular ejection fraction (LVEF during hospitalization (49.44% vs 42.94%; p<0.05. The follow-up after one year revealed still significantly higher BNP (365.49 vs 164.02 pg/ ml; p<0.05 and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs 54.41% and 39.52% vs 47.88%; p<0.05. Conclusion. Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

Optimization of treatment protocols to prevent de novo development of antibiotic resistance in Pseudomonas aeruginosa

NARCIS (Netherlands)

Feng, Yanfang

2016-01-01

The ever-increasing rate of drug resistant bacteria has been one of the most challenging problem worldwide. This thesis studied the following subjects with mostly the clinically leading pathogen, P. aeruginosa, as the model strain: de novo development of antibiotic resistance in patient during the

Coronary Artery Anomalies in Animals

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Brian A. Scansen

2017-04-01

Full Text Available Coronary artery anomalies represent a disease spectrum from incidental to life-threatening. Anomalies of coronary artery origin and course are well-recognized in human medicine, but have received limited attention in veterinary medicine. Coronary artery anomalies are best described in the dog, hamster, and cow though reports also exist in the horse and pig. The most well-known anomaly in veterinary medicine is anomalous coronary artery origin with a prepulmonary course in dogs, which limits treatment of pulmonary valve stenosis. A categorization scheme for coronary artery anomalies in animals is suggested, dividing these anomalies into those of major or minor clinical significance. A review of coronary artery development, anatomy, and reported anomalies in domesticated species is provided and four novel canine examples of anomalous coronary artery origin are described: an English bulldog with single left coronary ostium and a retroaortic right coronary artery; an English bulldog with single right coronary ostium and transseptal left coronary artery; an English bulldog with single right coronary ostium and absent left coronary artery with a prepulmonary paraconal interventricular branch and an interarterial circumflex branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae are also described including a coronary cameral fistula in a llama cria and an English bulldog with coronary artery aneurysm and anomalous shunting vessels from the right coronary artery to the pulmonary trunk. These examples are provided with the intent to raise awareness and improve understanding of such defects.

NOVO SISTEMA DE SEMEADURA CONSERVACIONISTA MULTIFUNCIONAL PARA A AGRICULTURA FAMILIAR: NOVO DRAGÃO/ NEW CONSERVATIONIST SYSTEM SEEDING FOR SMALL FARMS WITH MULTIFUNCTIONAL NEW DRAGON

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Daniel ALBIERO

2010-11-01

Full Text Available A agricultura familiar exerce papel importante na agricultura brasileira, sendo responsável por grande parcela da produção nacional de alimentos. No entanto não possui muitos equipamentos específicos para a semeadura. O objetivo principal deste trabalho foi o desenvolvimento e testes de um novo sistema de semeadura conservacionista para a agricultura familiar através de uma máquina multifuncional. Uma nova semeadora construída na filosofia de plantio em faixas com “Paraplow” Rotativo foi testada em campo em experimentos sob condições reais. Como resultado obteve-se um protótipo com bom desempenho na semeadura de soja, de fácil operação e manutenção, e principalmente adaptado às necessidades operacionais da agricultura familiar.Palavras-chaves: Sistema de semeadura, agricultura familiar, semedora multifuncional.

Association of aortic coarctation and malignant right coronary artery anomaly: an unusual cause of angina pectoris

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Sirtoli Filho R

2011-07-01

Full Text Available Rubens Sirtoli Filho1, Leonardo Cao Cãmbra de Almeida1, Maysa Godoy Gomes Mazurek Sirtoli1, Liliana Pena Pilatti2, Marcelo Valladão de Carvalho2, Marcelo Schafranski31Real e Benemérita Associação Portuguesa de Beneficência, São Paulo, Brazil; 2Department of Hemodynamics, 3Department of Intensive Care, Hospital Bom Jesus, Ponta Grossa, BrazilAbstract: A 53-year-old man with exercise-induced ischemia was referred for investigation. Coronary angiography revealed a right coronary artery originating from the trunk of the left coronary artery, and an aortic coarctation was observed on aortography. A CT angiogram confirmed these findings. Resection of the aortic coarctation and reimplantation of the ostial portion of right coronary artery into its native site was performed, and resulted in a satisfactory outcome. The association of an anomalous right coronary artery with aortic coarctation has rarely been described and represents a critical situation where early diagnosis and prompt intervention are essential.Keywords: coronary anomalies, single ostium, myocardial ischemia, angina pectoris

New noninvasive diagnosis of myocardial ischemia of the left circumflex coronary artery using coronary flow reserve measurement by transthoracic Doppler echocardiography. Comparison with thallium-201 single photon emission computed tomography

International Nuclear Information System (INIS)

Fujimoto, Kohei; Watanabe, Hiroyuki; Hozumi, Takeshi; Otsuka, Ryo; Hirata, Kumiko; Yamagishi, Hiroyuki; Yoshiyama, Minoru; Yoshikawa, Junichi

2004-01-01

The usefulness of coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography to detect myocardial ischemia was compared with exercise thallium-201 single photon emission computed tomography (SPECT). Transthoracic Doppler echocardiography was performed in 110 patients with suspected coronary artery disease. Color Doppler signals of the left circumflex coronary artery flow in the apical four-chamber view were identified, and the velocities at rest and during hyperemia recorded for calculation of coronary flow reserve by the pulsed Doppler method. All patients underwent SPECT within 1 week of the transthoracic Doppler echocardiographic study. Coronary flow reserve in the left circumflex coronary artery was measured in 79 (72%) of 110 patients. SPECT revealed reversible perfusion defect in the left circumflex coronary artery territories in 12 of 69 patients excluding those with multivessel disease. Coronary flow reserve <2.0 had a sensitivity of 92% and specificity of 96% for reversible perfusion defect detected by SPECT. Noninvasive coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography can estimate myocardial ischemia in the left ventricular lateral regions. (author)

Rapid hybrid de novo assembly of a microbial genome using only short reads: Corynebacterium pseudotuberculosis I19 as a case study.

Science.gov (United States)

Cerdeira, Louise Teixeira; Carneiro, Adriana Ribeiro; Ramos, Rommel Thiago Jucá; de Almeida, Sintia Silva; D'Afonseca, Vivian; Schneider, Maria Paula Cruz; Baumbach, Jan; Tauch, Andreas; McCulloch, John Anthony; Azevedo, Vasco Ariston Carvalho; Silva, Artur

2011-08-01

Due to the advent of the so-called Next-Generation Sequencing (NGS) technologies the amount of monetary and temporal resources for whole-genome sequencing has been reduced by several orders of magnitude. Sequence reads can be assembled either by anchoring them directly onto an available reference genome (classical reference assembly), or can be concatenated by overlap (de novo assembly). The latter strategy is preferable because it tends to maintain the architecture of the genome sequence the however, depending on the NGS platform used, the shortness of read lengths cause tremendous problems the in the subsequent genome assembly phase, impeding closing of the entire genome sequence. To address the problem, we developed a multi-pronged hybrid de novo strategy combining De Bruijn graph and Overlap-Layout-Consensus methods, which was used to assemble from short reads the entire genome of Corynebacterium pseudotuberculosis strain I19, a bacterium with immense importance in veterinary medicine that causes Caseous Lymphadenitis in ruminants, principally ovines and caprines. Briefly, contigs were assembled de novo from the short reads and were only oriented using a reference genome by anchoring. Remaining gaps were closed using iterative anchoring of short reads by craning to gap flanks. Finally, we compare the genome sequence assembled using our hybrid strategy to a classical reference assembly using the same data as input and show that with the availability of a reference genome, it pays off to use the hybrid de novo strategy, rather than a classical reference assembly, because more genome sequences are preserved using the former. Copyright © 2011 Elsevier B.V. All rights reserved.

De novo biosynthesis of volatiles induced by insect herbivory in cotton plants

International Nuclear Information System (INIS)

Pare, P.W.; Tumlinson, J.H.

1997-01-01

In response to insect feeding on the leaves, cotton (Gossypium hirsutum L.) plants release elevated levels of volatiles, which can serve as a chemical signal that attracts natural enemies of the herbivore to the damaged plant. Pulse-labeling experiments with [13C]CO2 demonstrated that many of the volatiles released, including the acyclic terpenes (E,E)-alpha-farnesene, (E)-beta-farnesene, (E)-beta-ocimene, linalool,(E)-4,8-dimethyl-1,3,7-nonatriene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetrane, as well as the shikimate pathway product indole, are biosynthesized de novo following insect damage. However, other volatile constituents, including several cyclic terpenes, butyrates, and green leaf volatiles of the lipoxygenase pathway are released from storage or synthesized from stored intermediates. Analysis of volatiles from artificially damaged plants, with and without beet armyworm (Spodoptera exigua Hubner) oral secretions exogenously applied to the leaves, as well as volatiles from beet armyworm-damaged and -undamaged control plants, demonstrated that the application of caterpillar oral secretions increased both the production and release of several volatiles that are synthesized de novo in response to insect feeding. These results establish that the plant plays an active and dynamic role in mediating the interaction between herbivores and natural enemies of herbivores

Single Center Retrospective Analysis of Conventional and Radial TIG Catheters for Transradial Diagnostic Coronary Angiography.

Science.gov (United States)

Vorpahl, Marc; Koehler, Till; Foerst, Jason; Panagiotopoulos, Spyridon; Schleiting, Heinrich; Koss, Klaus; Ziegler, Gunda; Brinkmann, Hilmar; Seyfarth, Melchior; Tiroch, Klaus

2015-01-01

Current guidelines favor the radial approach for coronary angiography. Therefore, specialty radial diagnostic catheters were designed to engage both coronary arteries with a single device. However, it is unclear if single catheters are superior to conventional catheters. A retrospective analysis was performed of consecutive right radial coronary angiographies to determine catheter use, fluoroscopy time, radiation dosage, and consumption of contrast. Procedures were performed with a single TIG catheter or conventional catheters (CONV). Procedures with coronary artery bypass grafts or ventricular angiographies were excluded. 273 transradial procedures were performed successfully. 95 procedures were performed with CONV and 178 procedures with a TIG. Crossover to additional catheters was higher in TIG (15.2%) compared to CONV (5.3%, p = 0.02). Fluoroscopy time was comparable between CONV and TIG, without crossover (2.2 ± 1.2 min versus 2.3 ± 1.2 min; n.s.), however, greater in the case of crossover for CONV (5.8 ± 0.7) and TIG (7.6 ± 3.0; p = 0.0001). Radiation dosage was similar in CONV and the TIG, without crossover (1419 ± 1075, cGy∗cm(2) versus 1690 ± 1138; n.s.), however, greater for CONV (2374 ± 620) and TIG (3733 ± 2281, p = 0.05) with crossover. Overall, the amount of contrast was greater in TIG (56 ± 13 mL) versus CONV (48 ± 3 mL; p = 0.0003). CONV femoral catheters may be the primary choice for radial approach.

Detection of coronary calcification in ultrafast CT compared to coronary angiography

International Nuclear Information System (INIS)

Koesling, S.; Hoffmann, U.; Rother, T.; Lieberenz, S.; Heywang-Koebrunner, S.H.; Schulz, H.G.

1994-01-01

The angiographical findings of 24 patients with coronary artery disease were compared with qualitative and quantitative detection of coronary calcification by ultrafast CT. Doubts concerning the capabilities of the ultrafast CT for a screening of coronary artery disease arise when the results of one third false positive and fase negative findings are considered. Variations in the quantification of coronary calcification were too great to allow a realistic assessment of the degree of stenosis of the coronary arteries. (orig.) [de

De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II.

Science.gov (United States)

Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan

2014-06-01

Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle.

Science.gov (United States)

Agerholm, Jørgen S; McEvoy, Fintan J; Heegaard, Steffen; Charlier, Carole; Jagannathan, Vidhya; Drögemüller, Cord

2017-08-02

Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS. High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire. FDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given

KeyPathwayMiner - De-novo network enrichment by combining multiple OMICS data and biological networks

DEFF Research Database (Denmark)

Baumbach, Jan; Alcaraz, Nicolas; Pauling, Josch K.

We tackle the problem of de-novo pathway extraction. Given a biological network and a set of case-control studies, KeyPathwayMiner efficiently extracts and visualizes all maximal connected sub-networks that contain mainly genes that are dysregulated, e.g., differentially expressed, in most cases ...

Novo Jornalismo: fronteiras litero-factuais em A sangue Frio e em Radical Chique

Directory of Open Access Journals (Sweden)

Francisco Aquinei Timóteo Queirós

2012-12-01

Full Text Available A pesquisa busca analisar de que forma fato e ficção se entrecruzam no “movimento” do Novo Jornalismo, a partir das obras A sangue Frio e Radical Chique e o Novo Jornalismo, de Truman Capote e Tom Wolfe, respectivamente. Pretende-se, a partir da investigação do corpus em estudo, revelar os aspectos que aproximam o fato jornalístico, a notícia e a reportagem às técnicas literárias do romance, do conto e da crônica. O estudo investiga o Novo Jornalismo sob o viés de textos centrais das áreas de teoria literária e estudos jornalísticos utilizando autores como Mikhail Bakhtin, Hayden White, Paul Ricoeur, Muniz Sodré; além de referenciar outros escritores que, como Tom Wolfe e Truman Capote, fizeram parte de um grande movimento renovador do jornalismo literário nos anos 1950, 1960 e 1970 chamado, genericamente, de Novo Jornalismo.

De novo formation of nucleoli in developing mouse embryos originating from enucleolated zygotes.

Science.gov (United States)

Kyogoku, Hirohisa; Fulka, Josef; Wakayama, Teruhiko; Miyano, Takashi

2014-06-01

The large, compact oocyte nucleoli, sometimes referred to as nucleolus precursor bodies (NPBs), are essential for embryonic development in mammals; in their absence, the oocytes complete maturation and can be fertilized, but no nucleoli are formed in the zygote or embryo, leading to developmental failure. It has been convincingly documented that zygotes inherit the oocyte nucleolar material and form NPBs again in pronuclei. It is commonly accepted that during early embryonic development, the original compact zygote NPBs gradually transform into reticulated nucleoli of somatic cells. Here, we show that zygote NPBs are not required for embryonic and full-term development in the mouse. When NPBs were removed from late-stage zygotes by micromanipulation, the enucleolated zygotes developed to the blastocyst stage and, after transfer to recipients, live pups were obtained. We also describe de novo formation of nucleoli in developing embryos. After removal of NPBs from zygotes, they formed new nucleoli after several divisions. These results indicate that the zygote NPBs are not used in embryonic development and that the nucleoli in developing embryos originate from de novo synthesized materials. © 2014. Published by The Company of Biologists Ltd.

De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal Correctional Clients.

Science.gov (United States)

DeLisi, Matt; Tahja, Katherine N; Drury, Alan J; Elbert, Michael J; Caropreso, Daniel E; Heinrichs, Timothy

2018-01-01

Adult antisocial behavior is almost always predated by delinquency during childhood or adolescence; however, there is also evidence of adult-onset criminal offending. This study examined this controversial subgroup of offenders using self-reported and official data from a total population of federal correctional clients selected from the Midwestern United States. Difference of means t-tests, chi-square tests, and logistic regression models found that 11.7% of clients had an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring at age 60 years or older. This group-introduced as de novo advanced adult-onset offenders-had high socioeconomic status, mixed evidence of adverse childhood experiences, and virtually no usage of drugs with the exception of alcohol. These offenders were primarily convicted of social security and white-collar crimes and evinced remarkably low psychopathology and criminal risk. More research is needed to replicate the phenomenon of de novo advanced adult-onset offending. © 2017 American Academy of Forensic Sciences.

CycloBranch: De Novo Sequencing of Nonribosomal Peptides from Accurate Product Ion Mass Spectra

Czech Academy of Sciences Publication Activity Database

Novák, Jiří; Lemr, Karel; Schug, K. A.; Havlíček, Vladimír

2015-01-01

Roč. 26, č. 10 (2015), s. 1780-1786 ISSN 1044-0305 R&D Projects: GA ČR(CZ) GAP206/12/1150 Grant - others:OPPC(XE) CZ.2.16/3.1.00/24023 Institutional support: RVO:61388971 Keywords : De novo sequencing * Nonribosomal peptides * Linear Subject RIV: CE - Biochemistry Impact factor: 3.031, year: 2015

Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

Science.gov (United States)

Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

2013-11-01

Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

Cinema utópico: a construção de um novo homem e um novo mundo

OpenAIRE

Erika Savernini Lopes

2011-01-01

O cinema, desde seus primórdios, prefigurou o espaço cibernético como um novo espaço imaterial construído coletivamente. A concepção desse outro lugar não físico para o qual o homem poderia migrar estabelece para o cinema e para o ciberespaço uma relação direta com as utopias. Na acepção do romance filosófico de Thomas More, a Utopia define-se como um outro espaço não-existente, irrealizável e ideal que diagnostica o atual. O cinema carregaria caracteres fundamentais da Utopia tanto no que se...

A multi-method approach toward de novo glycan characterization: a Man-5 case study.

Science.gov (United States)

Prien, Justin M; Prater, Bradley D; Cockrill, Steven L

2010-05-01

Regulatory agencies' expectations for biotherapeutic approval are becoming more stringent with regard to product characterization, where minor species as low as 0.1% of a given profile are typically identified. The mission of this manuscript is to demonstrate a multi-method approach toward de novo glycan characterization and quantitation, including minor species at or approaching the 0.1% benchmark. Recently, unexpected isomers of the Man(5)GlcNAc(2) (M(5)) were reported (Prien JM, Ashline DJ, Lapadula AJ, Zhang H, Reinhold VN. 2009. The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap mass spectrometry (MS). J Am Soc Mass Spectrom. 20:539-556). In the current study, quantitative analysis of these isomers found in commercial M(5) standard demonstrated that they are in low abundance (2-aminobenzoic acid to detect and chromatographically resolve multiple M(5) isomers in bovine ribonuclease B. With this multi-method approach, we have the capabilities to comprehensively characterize a biotherapeutic's glycan array in a de novo manner, including structural isomers at >/=0.1% of the total chromatographic peak area.

Os novos movimentos de protesto em França. A articulação de novas arenas públicas

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Daniel Cefaï

2012-10-01

Full Text Available Este artigo traça um panorama crítico da emergência dos novos movimentos de protesto (NMP em França, nas últimas décadas. Argumenta-se que desde meados dos anos oitenta, novas arenas públicas foram abertas pelos NMP, seguindo as transformações da sociedade salarial e da política pública, e respondendo à mundialização crescente dos mecanismos económicos, estratégicos e sociais. Para quem investe politicamente nos NMP, a importância da sua emergência reside no rearmamento da crítica social e na reconstituição de uma esquerda radical. Novos problemas públicos se impuseram aos cidadãos, aos especialistas e aos decisores políticos, em particular em torno da questão dos “sem documentos”, dos “sem trabalho” e dos “sem abrigo” mas também da saúde pública, da ecologia ou do consumo. Novos actores colectivos, ONGs, movimentos e coordenações tornaram-se os parceiros e os adversários incontornáveis dos poderes públicos. Contudo, alerta-se para o perigo destes movimentos resvalarem para uma acção político-partidária institucional, que poria em causa a acção concertada da esquerda política e a eficácia da sua actuação quer no contexto nacional quer no contexto europeu.

SÍNDROME CORONARIO AGUDO DE CAUSA NO ATEROESCLERÓTICA / Acute coronary syndrome of non-atherosclerotic origin

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Yuri Medrano Plana

2013-10-01

Full Text Available Resumen La embolia coronaria es una causa poco frecuente de síndrome coronario agudo. Dentro de los varios tipos de material embólico se encuentra el de origen tumoral. Estos émbolos pueden ocasionar isquemia miocárdica de intensidad variable, desde angina de pecho hasta infarto agudo de miocardio o incluso, muerte súbita. Se presenta una mujer de 58 años de edad, que presentó episodios de angina inestable con cambios eléctricos sin factores de riesgo y sin antecedentes de cardiopatía isquémica, que en la coronariografía se demostró la presencia de arterias coronarias normales. El ecocardiograma transesofágico informó imagen ecogénica polilobulada y pediculada hacia la superficie septal de la aurícula izquierda (posible mixoma, sin observarse trombos en las cavidades cardíacas. La paciente fue operada (exéresis quirúrgica del tumor, evolucionó favorablemente y fue trasladada a su hospital de origen 72 horas después. / Abstract Coronary embolism is a rare cause of acute coronary syndrome. Among the various types of embolic material is that of tumoral origin. These emboli can cause myocardial ischemia of varying intensity, from angina to acute myocardial infarction or even sudden death. The case of a 58-year-old woman who presented unstable angina episodes with electrical changes with no risk factors and no history of ischemic heart disease is presented. By means of coronary angiography, the presence of normal coronary arteries was showed. Transesophageal echocardiography showed the echogenic polylobulated and pedicled image towards the septal surface of the left atrium (possible myxoma; thrombi in the cardiac chambers were not observed. The patient underwent surgery (surgical removal of the tumor, had a good progress and was transferred to her hospital of origin 72 hours later.

De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation.

Science.gov (United States)

Kappus, Matthew; Abdelmalek, Manal

2017-05-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Coco de roda novo quilombo: saberes da cultura popular e práticas de educação popular na comunidade quilombola de Ipiranga no Conde-PB

OpenAIRE

Silva, Cicero Pedroza da

2014-01-01

O presente estudo, intitulado ―COCO DE RODE NOVO QUILOMBO: saberes da Cultura Popular e práticas de Educação Popular na comunidade quilombola de Ipiranga no Conde -PB‖, tem como objetivo central analisar a contribuição histórica, cultural social e política da comunidade quilombola de Ipiranga no Conde-PB para a construção de práticas educativas na perspectiva freireana de Educação Popular. Situada, metodologicamente, nos preceitos da abordagem qualitativa de pesquisa, enquanto pes...

De novo transcriptomic analysis of an oleaginous microalga: pathway description and gene discovery for production of next-generation biofuels.

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LingLin Wan

Full Text Available Eustigmatos cf. polyphem is a yellow-green unicellular soil microalga belonging to the eustimatophyte with high biomass and considerable production of triacylglycerols (TAGs for biofuels, which is thus referred to as an oleaginous microalga. The paucity of microalgae genome sequences, however, limits development of gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for a non-model microalgae species, E. cf. polyphem, and identify pathways and genes of importance related to biofuel production.We performed the de novo assembly of E. cf. polyphem transcriptome using Illumina paired-end sequencing technology. In a single run, we produced 29,199,432 sequencing reads corresponding to 2.33 Gb total nucleotides. These reads were assembled into 75,632 unigenes with a mean size of 503 bp and an N50 of 663 bp, ranging from 100 bp to >3,000 bp. Assembled unigenes were subjected to BLAST similarity searches and annotated with Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG orthology identifiers. These analyses identified the majority of carbohydrate, fatty acids, TAG and carotenoids biosynthesis and catabolism pathways in E. cf. polyphem.Our data provides the construction of metabolic pathways involved in the biosynthesis and catabolism of carbohydrate, fatty acids, TAG and carotenoids in E. cf. polyphem and provides a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock.

Endovascular gamma-irradiation for prevention of restenosis after angioplasty of femoropopliteal de-novo-stenoses. Long-term results of a feasibility study

International Nuclear Information System (INIS)

Krueger, K.; Zaehringer, M.; Schulte, O.; Lackner, K.; Bendel, M.; Bongartz, R.; Nolte, M.

2002-01-01

Objectives: To evaluate the performance and efficacy of endovascular irradiation after percutaneous transluminal angioplasty (PTA) of de-novo femoropopliteal stenoses in a pilot study. Methods: 6 patients received non-centered endovascular irradiation (12 Gray at surface of the vessel wall) immediately after angioplasty of de-novo femoropopliteal stenosis, 1 patient was given centered endovascular irradiation using 192-iridium (12 Gray at surface of the vessel wall) Centered irradiation was considered for two other patients. Duplex sonographies and interviews were performed the day before and after PTA and after 1, 3, 6, 9, 12, 18, 24 months up to 4 years. Intraarterial angiography was performed in symptomatic patients. Results: Non-centered endovascular irradiation was possible in all patiens without problems or complications. Centered irradiation was not possible in two patients with the cross-over approach. One thromboembolic complication occurred during centered irradiation. Both restenosis and new stenosis at the edge of irradiated distance occurred in 1/7 patiens. No other side effects were observed during follow-up. Conclusions: In our pilot study endovascular irradiation after angioplasty of de-novo femoropopliteal stenosis was possible with low rates of complications and restenosis and taking vessel anatomy into account. (orig.) [de

Detecção de casos novos de hanseníase no município de Prudentópolis, PR: uma análise de 1998 a 2005

OpenAIRE

Sanches,Lucas Augusto Thomé; Pittner,Elaine; Sanches,Hermes Francisco; Monteiro,Marta Chagas

2007-01-01

Este trabalho teve como objetivo detectar os casos novos de hanseníase do período de 1998 a 2005 no município de Prudentópolis, PR. Assim como, verificar a faixa etária e a forma clínica predominante entre os casos de hanseníase. Os dados foram obtidos através das fichas clínico-epidemiológicas de casos com diagnóstico definitivo de hanseníase notificado no Sistema de Informação sobre Agravos de Notificação, de 1998 a 2005. Neste período, foram relatados 222 casos de hanseníase, dos quais 63%...

De Novo Nodal Diffuse Large B-Cell Lymphoma: Identification of Biologic Prognostic Factors

International Nuclear Information System (INIS)

Abd El-Hameed, A.

2005-01-01

Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients. making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t( 14; 18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. Material and Methods: A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formal infixed, paraffin-embedded sections were analyzed for: I) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR). and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. Bcl-2 gene rearrangement was detected in 8 cases (20%). 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (> I 0%) was expressed in 24 cases (60%), irrespective of the presence of t( 14; 18) translocation. The t( 14; 18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (ρ=0.008. and 0.04. respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (ρ=0.04, and 0.01, respectively). The t( 14; 18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the

Caracterização de novos isolados de Bacillus thuringiensis para o controle de importantes insetos-praga da agricultura

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Emeline Boni Campanini

2012-01-01

Full Text Available A bactéria Bacillus thuringiensis Berliner produz um corpo de inclusão paraesporal (cristal de natureza proteica, formado durante a esporulação, que atua de forma eficiente no controle de insetos-praga de culturas economicamente importantes. Esse cristal é constituído de proteínas Cry, que são codificadas pelos genes cry; um isolado pode ser caracterizado pelo conteúdo de genes cry que apresenta. Visando caracterizar novos isolados no combate de insetos-praga pertencentes às ordens Lepidoptera e Coleoptera, 76 isolados bacterianos foram analisados molecularmente e tiveram seu potencial de controle avaliado por meio de bioensaios com larvas de Spodoptera frugiperda (J.E. Smith, Sphenophorus levis Vaurie e Tenebrio molitor Linnaeus. As análises moleculares indicaram 11 isolados (14,5% da coleção, contendo genes lepidóptero-específicos e 17 (22,37% com genes coleóptero-específicos. As análises de patogenicidade revelaram dois isolados com alto potencial de controle para lagartas de S. frugiperda, um para larvas de S. levis e seis prejudiciais ao desenvolvimento das larvas de T. molitor. Esses isolados de B. thuringiensis podem ser promissores no controle biológico das referidas pragas.

Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats

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Mélanie Campana

2018-02-01

Full Text Available Objectives: Hypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity. Methods: Hypothalamic GT1-7 neuronal cells were treated with palmitate. De novo ceramide synthesis was inhibited either by pharmacological (myriocin or molecular (si-Serine Palmitoyl Transferase 2, siSPT2 approaches. Obese Zucker rats (OZR were intracerebroventricularly infused with myriocin to inhibit de novo ceramide synthesis. Insulin resistance was determined by quantification of Akt phosphorylation. Ceramide levels were quantified either by a radioactive kinase assay or by mass spectrometry analysis. Glucose homeostasis were evaluated in myriocin-treated OZR. Basal and glucose-stimulated parasympathetic tonus was recorded in OZR. Insulin secretion from islets and β-cell mass was also determined. Results: We show that palmitate impaired insulin signaling and increased ceramide levels in hypothalamic neuronal GT1-7 cells. In addition, the use of deuterated palmitic acid demonstrated that palmitate activated several enzymes of the de novo ceramide synthesis pathway in hypothalamic cells. Importantly, myriocin and siSPT2 treatment restored insulin signaling in palmitate-treated GT1-7 cells. Protein kinase C (PKC inhibitor or a dominant-negative PKCζ also counteracted palmitate-induced insulin resistance. Interestingly, attenuating the increase in levels of hypothalamic ceramides with intracerebroventricular infusion of myriocin in OZR improved their hypothalamic insulin-sensitivity. Importantly, central myriocin treatment partially restored glucose tolerance in OZR. This latter effect is related to the restoration of glucose-stimulated insulin

De novo SOX11 mutations cause Coffin-Siris syndrome.

Science.gov (United States)

Tsurusaki, Yoshinori; Koshimizu, Eriko; Ohashi, Hirofumi; Phadke, Shubha; Kou, Ikuyo; Shiina, Masaaki; Suzuki, Toshifumi; Okamoto, Nobuhiko; Imamura, Shintaro; Yamashita, Michiaki; Watanabe, Satoshi; Yoshiura, Koh-ichiro; Kodera, Hirofumi; Miyatake, Satoko; Nakashima, Mitsuko; Saitsu, Hirotomo; Ogata, Kazuhiro; Ikegawa, Shiro; Miyake, Noriko; Matsumoto, Naomichi

2014-06-02

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by growth deficiency, intellectual disability, microcephaly, characteristic facial features and hypoplastic nails of the fifth fingers and/or toes. We previously identified mutations in five genes encoding subunits of the BAF complex, in 55% of CSS patients. Here we perform whole-exome sequencing in additional CSS patients, identifying de novo SOX11 mutations in two patients with a mild CSS phenotype. sox11a/b knockdown in zebrafish causes brain abnormalities, potentially explaining the brain phenotype of CSS. SOX11 is the downstream transcriptional factor of the PAX6-BAF complex, highlighting the importance of the BAF complex and SOX11 transcriptional network in brain development.

UM NOVO MÉTODO PARA CARACTERIZAÇÃO DE PROPRIEDADES MECÂNICAS EM MATERIAIS CERÂMICOS

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Eduardo A. de Carvalho

2010-05-01

Full Text Available As dificuldades de propriedades mecânicas em materiais cerâmicos, seja pela fragilidade intrínseca do material, seja pelo desalinhamento de barras de tração nos métodos tradicionais utilizados para metais, levou à proposição de um novo método de trabalho. O método proposto não se utiliza de contatos mecânicos para a aplicação de carregamento, porém de radiação de uma emissão laser. Aqui é apresentado um caso estudado onde o método determina, com sucesso, a Tenacidade, a Fratura de um corpo de prova em forma de disco feito de nitreto e silício.

De novo assembly of a 40 Mb eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis.

Science.gov (United States)

Nowrousian, Minou; Stajich, Jason E; Chu, Meiling; Engh, Ines; Espagne, Eric; Halliday, Karen; Kamerewerd, Jens; Kempken, Frank; Knab, Birgit; Kuo, Hsiao-Che; Osiewacz, Heinz D; Pöggeler, Stefanie; Read, Nick D; Seiler, Stephan; Smith, Kristina M; Zickler, Denise; Kück, Ulrich; Freitag, Michael

2010-04-08

Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30-90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in approximately 4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for

De novo assembly of a 40 Mb eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis.

Directory of Open Access Journals (Sweden)

Minou Nowrousian

2010-04-01

Full Text Available Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30-90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in approximately 4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data

Clinical correlation of the binding potential with {sup 123}I-FP-CIT in de novo idiopathic Parkinson's disease patients

Energy Technology Data Exchange (ETDEWEB)

Berti, Valentina; Pupi, Alberto; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia; Marini, Paolo; Sorbi, Sandro [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

2008-12-15

The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-{omega}-fluoropropyl-2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]iodophenyl-nortropane ({sup 123}I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Thirty-six de novo PD patients underwent {sup 123}I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal {sup 123}I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP{sub FBP}, BP{sub OSEM}, BP{sub LS}). The range of values of striatal BP{sub LS} was significantly greater than BP{sub FBP} and BP{sub OSEM}. For all striatal regions, estimates of BP{sub FBP} correlated well with BP{sub OSEM} (r=0.84) and with BP{sub LS} (r=0.64); BP{sub OSEM} correlated significantly with BP{sub LS} (r=0.76). A good correlation was found between putaminal BP{sub LS} and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r=-0.46, r=-0.42, r=-0.39, respectively). Neither putaminal BP{sub FBP} nor putaminal BP{sub OSEM} correlated with any of these motor scores. In de novo PD patients, {sup 123}I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of {sup 123}I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity. (orig.)

Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens.

Science.gov (United States)

Grant, M B; Wargovich, T J; Ellis, E A; Tarnuzzer, R; Caballero, S; Estes, K; Rossing, M; Spoerri, P E; Pepine, C

1996-12-17

The molecular and cellular processes that induce rapid atherosclerotic plaque progression in patients with unstable angina and initiate restenosis following coronary interventional procedures are uncertain. We examined primary (de novo) and restenotic lesions retrieved at the time of directional coronary atherectomy for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its receptor and binding proteins were not detected in SMCs of normal coronary arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I receptor was significantly higher in de novo lesions as compared to restenotic lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P system.

Síntese e caracterização de novos copolímeros fosforilados

Directory of Open Access Journals (Sweden)

Viviane Martins Rebello dos Santos

2015-12-01

Full Text Available Resumo O rápido desenvolvimento da química de polímeros nos últimos anos tem acompanhado a introdução dos materiais poliméricos no campo da medicina. Polímeros com aplicações médicas podem ser subdivididos em dois grandes grupos: materiais usados em próteses e a produção de polímeros biologicamente ativos. Neste trabalho foram sintetizados copolímeros possuindo cadeia principal de poli (metacrilato de metila e cadeias enxertadas de polietilenoglicol (COP GRAFT. A partir da síntese do copolímero enxertado inicial foram realizadas modificações em suas cadeias de modo a aumentar a possibilidade de incorporação de um fármaco que será utilizado em sistema de liberação controlada de medicamentos. Os novos compostos foram obtidos através de duas rotas sintéticas e os produtos formados ao final de cada etapa foram purificados e caracterizados. Através da técnica de infravermelho (FITIR foi possível observar as bandas de absorções características das ligações P-H, P=O e P-O, que foram inseridas na cadeia do COP GRAFT durante a fosforilação, além das bandas de absorções características do copolímero, antes da fosforilação, como C=O e C-O. A caracterização térmica das amostras utilizando termogravimetria (TGA e calorimetria diferencial de varredura (DSC mostrou que apenas o copolímero de diisobutila apresentou temperatura de transição endotérmica e comportamentos de degradação compatíveis a de um polímero. Através da técnica de difração de raios X (XRD foi possível observar uma modificação da cristalinidade das amostras, provavelmente devido a uma variação da conformação das cadeias após a inserção de novos grupos químicos. Nos cromatogramas obtidos pela técnica de cromatografia de permeação em gel (GPC percebeu-se aumento de massa após a fosforilação com o grupo diisobutila no COPGRAFT. A reação de fosforilação foi eficiente na obtenção do copolímero de diisobutila e as t

Identification of optimum sequencing depth especially for de novo genome assembly of small genomes using next generation sequencing data.

Science.gov (United States)

Desai, Aarti; Marwah, Veer Singh; Yadav, Akshay; Jha, Vineet; Dhaygude, Kishor; Bangar, Ujwala; Kulkarni, Vivek; Jere, Abhay

2013-01-01

Next Generation Sequencing (NGS) is a disruptive technology that has found widespread acceptance in the life sciences research community. The high throughput and low cost of sequencing has encouraged researchers to undertake ambitious genomic projects, especially in de novo genome sequencing. Currently, NGS systems generate sequence data as short reads and de novo genome assembly using these short reads is computationally very intensive. Due to lower cost of sequencing and higher throughput, NGS systems now provide the ability to sequence genomes at high depth. However, currently no report is available highlighting the impact of high sequence depth on genome assembly using real data sets and multiple assembly algorithms. Recently, some studies have evaluated the impact of sequence coverage, error rate and average read length on genome assembly using multiple assembly algorithms, however, these evaluations were performed using simulated datasets. One limitation of using simulated datasets is that variables such as error rates, read length and coverage which are known to impact genome assembly are carefully controlled. Hence, this study was undertaken to identify the minimum depth of sequencing required for de novo assembly for different sized genomes using graph based assembly algorithms and real datasets. Illumina reads for E.coli (4.6 MB) S.kudriavzevii (11.18 MB) and C.elegans (100 MB) were assembled using SOAPdenovo, Velvet, ABySS, Meraculous and IDBA-UD. Our analysis shows that 50X is the optimum read depth for assembling these genomes using all assemblers except Meraculous which requires 100X read depth. Moreover, our analysis shows that de novo assembly from 50X read data requires only 6-40 GB RAM depending on the genome size and assembly algorithm used. We believe that this information can be extremely valuable for researchers in designing experiments and multiplexing which will enable optimum utilization of sequencing as well as analysis resources.

Proposta de seleção e priorização do portfólio de novos produtos em uma empresa têxtil

Directory of Open Access Journals (Sweden)

Mauricio Johnny Loos

2016-01-01

Full Text Available Resumo A gestão de portfólio de produtos é um dos processos responsáveis por manter a posição competitiva das organizações, alocar adequadamente os recursos de desenvolvimento e assegurar maior objetividade e eficácia na seleção dos projetos de novos produtos. Assim sendo, empresas de diversos setores industriais vêm estruturando seus processos de gestão de portfólio no processo de desenvolvimento de produtos (PDP. Nesse contexto, o presente trabalho objetiva desenvolver uma proposta de seleção e priorização de projetos de novos produtos voltada para uma empresa fabricante de produtos têxteis. Com base em um diagnóstico inicial para identificar oportunidades de melhoria na gestão de portfólio de produtos, é feita uma proposta baseada em critérios tais como: importância estratégica, margem de contribuição, volume de venda previsto, dentre outros. A proposta foi então confrontada com dados históricos advindos de situação real, onde constataram-se alterações significativas na priorização dos produtos a serem desenvolvidos, devido a alguns fatores, dentre os quais os principais foram o superdimensionamento das margens de contribuição e dos volumes de venda. Por meio da comparação na aplicação da proposta, conclui-se que esta possibilita que a seleção e priorização de produtos a serem desenvolvidos pela empresa ocorram de forma mais bem estruturada e criteriosa.

A Terra em Transe: o cosmopolitismo às avessas do cinema novo

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Angela Prysthon

2008-11-01

Full Text Available Usando como referencial teórico os estudos culturais, este artigo analisa o cinema novo brasileiro como parte de uma estratégia terceiro mundista de conceber a cultura. A partir da emergência do conceito de terceiro mundo e das lutas de descolonização nos anos 1950 e 1960, a ideologia cosmopolita foi sendo vista pelos intelectuais de esquerda como a versão cultural da aliança com as forças hegemônicas da Europa e dos Estados Unidos. O projeto do cinema novo chama a atenção por suas afinidades ideológicas com o terceiro mundismo, mas, paradoxalmente, trazendo à tona uma polí­tica cosmopolita da periferia. Palavras-chave cinema novo, identidade, cultura brasileira, terceiro mundismo, estudos culturais. Abstract Using the cultural studies theoretical framework, this paper analyzes the cinema novo movement in Brazil as a part of the Third World conception of culture. Following the creation of the term "Third World" and the international politics of colonial independence of the 1950s and 1960s, a cosmopolitan attitude was seen by the intellectuals of the left as a cultural version of the alliance with the hegemonic forces of Europe and North America. Even though the cinema novo project can be associated with the ideology of an united Third World ,it brings about, paradoxically, a very cosmopolitan politics of the periphery. Key words cinema novo, identity, Brazilian culture, third world, cultural studies.

Improved outcome with novel device for low-pressure PTCA in de novo and in-stent lesions

International Nuclear Information System (INIS)

Ischinger, Thomas A.; Solar, Ronald J.; Hitzke, Evelyn

2003-01-01

Purpose: Complex lesion morphology requiring the use of high pressure to effect lumen expansion and in-stent restenosis (ISR) remain two indications that challenge conventional PTCA balloons. We report on a new PTCA device that is designed to provide precise, low-pressure dilatation of both de novo and in-stent lesions. Methods: The FX miniRAIL catheter (FX) has an integral wire positioned external to a dilating balloon and a short, 12-mm guidewire lumen distal to the balloon. The balloon inflates against the guidewire and the external wire to prevent slippage and to introduce high focal longitudinal stresses at low inflation pressures. In this initial study, the FX was used in 37 lesions (25 de novo, 12 in-stent; vessel reference diameter=2.73±0.49 mm) in 30 patients. A stepwise inflation protocol and QCA were used to determine the balloon pressure at which the stenosis was resolved (stenosis resolution pressure, SRP). Results: All lesions (100%) were easily reached, crossed and dilated without complication. The SRP was 4.5±2.9 atm, and no balloon slippage was observed. Residual stenosis after FX was 26.39±13.29%. Minor dissections (Types A and B) were observed in eight lesions (21.6%). Target lesion revascularization (TLR) and target vessel revascularization (TVR) at follow-up (8.1±1.5 months) were 8.3% and 12.5%, respectively. Conclusion: The design of the FX is versatile and appears to provide for a safe, effective and improved low-pressure PTCA technique in de novo and in-stent lesions

Management for Patients with De Novo or Recurrent Tumors in the Residual Kidney after Surgery for Nonfamilial Bilateral Renal Cell Carcinoma

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Noboru Hara

2009-01-01

Full Text Available The tumor de novo in the residual kidney after surgery for nonfamilial bilateral renal cell carcinoma (RCC is problematic. We reviewed 5 patients who experienced such a situation. Three patients had had metachronous bilateral RCC, treated with radical nephrectomy in one kidney and nephron-sparing surgery (NSS in the other. Two patients had had synchronous disease; one patient had received radical nephrectomy and NSS, and the other bilateral NSS. The 5 patients had another solid mass/de novo tumor in the residual kidney 16–88 (mean 46.8 months after surgery. For the tumor de novo in earlier years (1992–1999, one patient underwent surgery and hemodialysis, and the other selected a conservative observation. In recent years (2000–2007, one patient was conservatively observed; the remaining 2 received computerized-tomography-guided radiofrequency ablation, and the local tumors were well controlled postoperatively for 20 and 12 months with their renal function unimpaired. Ablative techniques can potentially strike a balance between oncological and nephrological outcomes in patients with sporadic multiple RCC, successful management of which was difficult previously.

Icarus: visualizer for de novo assembly evaluation.

Science.gov (United States)

Mikheenko, Alla; Valin, Gleb; Prjibelski, Andrey; Saveliev, Vladislav; Gurevich, Alexey

2016-11-01

: Data visualization plays an increasingly important role in NGS data analysis. With advances in both sequencing and computational technologies, it has become a new bottleneck in genomics studies. Indeed, evaluation of de novo genome assemblies is one of the areas that can benefit from the visualization. However, even though multiple quality assessment methods are now available, existing visualization tools are hardly suitable for this purpose. Here, we present Icarus-a novel genome visualizer for accurate assessment and analysis of genomic draft assemblies, which is based on the tool QUAST. Icarus can be used in studies where a related reference genome is available, as well as for non-model organisms. The tool is available online and as a standalone application. http://cab.spbu.ru/software/icarus CONTACT: aleksey.gurevich@spbu.ruSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evangelização que comunica e Comunicação que evangeliza: Comunidade Canção Nova, um novo jeito de ser igreja a partir do entrecruzamento evangelização-comunicação

OpenAIRE

Nivia Ivette Núñez de la Paz

2008-01-01

A tese tem como objetivo principal demonstrar, a partir de argumentos que emergem do entrecruzamento Evangelização-Comunicação, que a Comunidade Canção Nova representa um Novo Jeito de ser Igreja dentro do catolicismo romano. Os argumentos que denotam, balizam e sustentam tal afirmação são: os novos jeitos de comunidades, os novos jeitos de famílias e os novos jeitos de identidades que convivem nesse fenômeno religioso-carismático-midiático. Esses argumentos afloraram na pesquisa do cotidiano...

De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature

DEFF Research Database (Denmark)

Becker, Kerstin; Di Donato, Nataliya; Holder-Espinasse, Muriel

2012-01-01

with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.......3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14...

76 FR 61103 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Science.gov (United States)

2011-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... appropriate, and other forms of information technology. Draft Guidance for Industry and Food and Drug...

TRANSPORT OF PATIENTS FOR PRIMARY PTCA FROM GENERAL HOSPITAL NOVO MESTO TO LJUBLJANA IN 2002

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Renata Okrajšek

2004-12-01

Full Text Available Background. The treatment of acute coronary syndrome (ACS with ST-segment elevation with primary percutaneous transluminal coronary angioplasty (PTCA is the best way to treat these patients. Primary PTCA is also practicable with patients who are admitted into institution without catheter laboratory. The transport of patients into the tertiary institution is safe, but it is important to keep the time of ischemia as short as possible and to reach the time interval of door-balloon as recommended by the guidelines. The ACS patients with ST-segment elevation that were directed into General Hospital Novo mesto after examination at the internistic emergency department have been redirected to KC Ljubljana for realization of PTCA since October 2001.Methods. A prospective analysis of patients with ACS with STsegment elevation, who had been transferred from General Hospital Novo mesto to KC Ljubljana in the period from January 1, 2002 to December 31, 2002 to have a primary PTCA, was performed. The analysis comprised the following: the time interval of handling the patients at Internistic department of General Hospital Novo mesto, the time of transport of patients to Ljubljana and total time interval from the arrival of patients to General Hospital Novo mesto to the first inflation of balloon in Ljubljana. We monitored the complications that occurred during the treatment of the patients.Results. In the above mentioned period 29 patients (24 males and 5 females were transported from the General Hospital Novo mesto to the KC Ljubljana to have a primary PTCA performed. The total time interval measured between the patients’ arrival to General Hospital Novo mesto to the first inflation of balloon in Ljubljana in the year 2002 was 145 minutes, which is 17 minutes better than in the previous period. The time interval recommended by the guidelines was achieved with four patients.Conclusions. By recognizing the problems that had encountered with directing the