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101.
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Ewelina Grywalska Jacek Roliński Marcin Pasiarski Izabela Korona-Glowniak Maciej Maj Agata Surdacka Agnieszka Grafka Agnieszka Stelmach-Go?dy? Micha? Zgurski Stanis?aw Gó?d? Anna Malm Piotr Grabarczyk El?bieta Staros?awska 《PloS one》2015,10(10)
Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL. 相似文献
104.
Emanuela Carlotti David Wrench Guglielmo Rosignoli Jacek Marzec Ajanthah Sangaralingam Lena Hazanov Miri Michaeli Simon Hallam Tracy Chaplin Sameena Iqbal Maria Calaminici Bryan Young Ramit Mehr Peter Campbell Jude Fitzgibbon John G. Gribben 《PloS one》2015,10(9)
Understanding the dynamics of evolution of Follicular Lymphoma (FL) clones during disease progression is important for monitoring and targeting this tumor effectively. Genetic profiling of serial FL biopsies and examples of FL transmission following bone marrow transplant suggest that this disease may evolve by divergent evolution from a common ancestor cell. However where this ancestor cell resides and how it evolves is still unclear. The analysis of the pattern of somatic hypermutation of the immunoglobulin gene (Ig) is traditionally used for tracking the physiological clonal evolution of B cells within the germinal center and allows to discriminate those cells that have just entered the germinal center and display features of ancestor cells from those B cells that keep re-circulating across different lymphoid organs. Here we investigated the pattern of somatic hypermutation of the heavy chain of the immunoglobulin gene (IgH-VH) in 4 flow-sorted B cells subpopulations belonging to different stages of differentiation, from sequential lymph node biopsies of cases displaying diverse patterns of evolution, using the GS-FLX Titanium sequencing platform. We observed an unexpectedly high level of clonality, with hundreds of distinct tumor subclones in the different subpopulations from the same sample, the majority detected at a frequency <10−2. By using a lineage trees analysis we observed in all our FL and t-FL cases that the oligoclonal FL population was trapped in a narrow intermediate stage of maturation that maintains the capacity to undergo SHM, but was unable to further differentiate. The presence of such a complex architecture highlights challenges currently encountered in finding a cure for this disease. 相似文献
105.
Chandree?L. Beaulieu Jacek Majewski Jeremy Schwartzentruber Mark?E. Samuels Bridget?A. Fernandez Francois?P. Bernier Michael Brudno Bartha Knoppers Janet Marcadier David Dyment Shelin Adam Dennis?E. Bulman Steve?J.M. Jones Denise Avard Minh?Thu Nguyen Francois Rousseau Christian Marshall Richard?F. Wintle Yaoqing Shen Stephen?W. Scherer FORGE Canada Consortium Jan?M. Friedman Jacques?L. Michaud Kym?M. Boycott 《American journal of human genetics》2014,94(6):809-817
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE’s impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. 相似文献
106.
Ranad Shaheen Hanan E. Shamseldin Catrina M. Loucks Mohammed Zain Seidahmed Shinu Ansari Mohamed Ibrahim Khalil Nadya Al-Yacoub Erica E. Davis Natalie A. Mola Katarzyna Szymanska Warren Herridge Albert E. Chudley Bernard N. Chodirker Jeremy Schwartzentruber Jacek Majewski Nicholas Katsanis Coralie Poizat Colin A. Johnson Jillian Parboosingh Kym M. Boycott A. Micheil Innes Fowzan S. Alkuraya 《American journal of human genetics》2014
107.
Fluorescence methods (VistaCam iX proof and DIAGNODent pen) for the detection of occlusal carious lesions in teeth recovered from archaeological context 下载免费PDF全文
Jacek Tomczyk Julian Komarnitki Marta Zalewska Tomasz Lekszycki Dorota Olczak‐Kowalczyk 《American journal of physical anthropology》2014,154(4):525-534
Diagnosis of occlusal enamel caries in archaeologically derived collections remains a controversial problem because the accumulation of contaminants in fissures can interfere with diagnosis. Certain novel light‐induced fluorescence methods, such as the DIAGNODent pen 2190 (DD) and VistaCam iX Proof (VC), have been used to detect dental caries in clinical settings. In this study, the abilities of DD and VC to detect initial enamel caries in archaeologically derived material is determined and compared with those of other methods (visual inspection, X‐ray, histology, and micro‐CT). Dental material encompassing the remains of 58 individuals, including a total of 380 teeth from each of three historical periods: modern Islamic (AD 1850–1950), Islamic (AD 600–1200) and late Roman (AD 200–400), obtained from two archaeological sites (Terqa and Tell Masaikh) located in the Middle Euphrates valley (Syria), were analyzed. VC was found to have excellent sensitivity (98), while DD obtained lower sensitivity (76) in detecting dental caries in its early stages. The results obtained by VC and micro‐CT, considered the most reliable imaging technique, were not statistically significant (P = 0.3068). By contrast, results obtained by DD and micro‐CT results, and DD and VC results were statistically significant (P < 0.0001, P = 0.0015, respectively). However the presence of dirt, stain, calculus, and plaque in the pits and fissures of the occlusal surface compromise correct diagnosis of caries by VC and DD. Consequently, for teeth recovered from archaeological contexts where staining, calculus and plaque are present, the best solution remains micro‐CT. Am J Phys Anthropol 154:525–534, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
108.
Jacek Wierzchowski Alicja Stachelska-Wierzchowska Beata Wielgus-Kutrowska Goran Mikleušević 《Analytical biochemistry》2014
Two nontypical nucleosides, 7-β-d-ribosyl-2,6-diamino-8-azapurine and 8-β-d-ribosyl-2,6-diamino-8-azapurine, have been found to exhibit moderately good, and selective, substrate properties toward calf and bacterial (Escherichia coli) forms of purine nucleoside phosphorylase (PNP). The former compound is effectively phosphorolysed by calf PNP and the latter by PNP from E. coli. Both compounds are fluorescent with λmax ∼ 425 to 430 nm, but the reaction product, 2,6-diamino-8-azapurine, emits in a different spectral region (λmax ∼ 363 nm) with nearly 40% yield, providing a strong fluorogenic effect at 350 to 360 nm. 相似文献
109.
Agata Plesnar Bielak Anna M. Skrzynecka Krzysztof Miler Jacek Radwan 《Evolution; international journal of organic evolution》2014,68(7):2137-2144
Intralocus sexual conflict (IASC) arises when fitness optima for a shared trait differ between the sexes; such conflict may help maintain genetic variation within populations. Sex‐limited expression of sexually antagonistic traits may help resolve the conflict, but the extent of this resolution remains a subject of debate. In species with alternative male reproductive tactics, unresolved conflict should manifest more in a more sexually dimorphic male phenotype. We tested this prediction in the bulb mite (Rhizoglyphus robini), a species in which aggressive fighters coexist with benign scramblers. To do this, we established replicated lines in which we increased the proportion of each of the alternative male morphs using artificial selection. After approximately 40 generations, the proportion of fighters and scramblers stabilized at >0.9 in fighter‐ and scrambler‐selected lines, respectively. We then measured several female fitness components. As predicted by IASC theory, female fecundity and longevity were lower in lines selected for fighters and higher in lines selected for scramblers. This finding indicates that sexually selected phenotypes are associated with an ontogenetic conflict that is not easily resolved. Furthermore, we suggest that IASC may be an important mechanism contributing to the maintenance of genetic variation in the expression of alternative reproductive tactics. 相似文献
110.
Aleksandra Kwiatkowska Jacek Zebrowski Bernadetta Oklejewicz Justyna Czarnik Joanna Halibart-Puzio Maciej Wnuk 《Biochemical and biophysical research communications》2014
Plant cell suspension cultures represent good model systems applicable for both basic research and biotechnological purposes. Nevertheless, it is widely known that a prolonged in vitro cultivation of plant cells is associated with genetic and epigenetic instabilities, which may limit the usefulness of plant lines. In this study, the age-dependent epigenetic and physiological changes in an asynchronous Arabidopsis T87 cell culture were examined. A prolonged cultivation period was found to be correlated with a decrease in the proliferation rate and a simultaneous increase in the expression of senescence-associated genes, indicating that the aging process started at the late growth phase of the culture. In addition, increases in the heterochromatin-specific epigenetic markers, i.e., global DNA methylation, H3K9 dimethylation, and H3K27 trimethylation, were observed, suggesting the onset of chromatin condensation, a hallmark of the early stages of plant senescence. Although the number of live cells decreased with an increase in the age of the culture, the remaining viable cells retained a high potential to efficiently perform photosynthesis and did not exhibit any symptoms of photosystem II damage. 相似文献