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  • 1
    Language: English
    In: Leukemia, 2017-01, Vol.31 (1), p.18-25
    Description: Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, 〈0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P〈0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P〈0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.
    Subject(s): fms-Like Tyrosine Kinase 3 - genetics ; Disease-Free Survival ; Leukemia, Myeloid, Acute - diagnosis ; Prognosis ; Epigenesis, Genetic - genetics ; Humans ; Child, Preschool ; Retrospective Studies ; Gene Expression Regulation, Leukemic ; Child ; Neoplasm, Residual - genetics ; Leukemia, Myeloid, Acute - genetics ; Molecular targeted therapy ; Gene mutations ; Gene expression ; Health aspects ; Innovations ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Leukemia, 2008-12, Vol.22 (12), p.2193-2200
    Description: The aim of the study was to analyze the impact of minimal residual disease (MRD) after reinduction therapy on the outcome of children with relapsed 'high-risk' acute lymphoblastic leukemia (ALL). Sixty patients with isolated or combined marrow relapse were studied. All patients belonged to the S3 or S4 groups, as defined by the Berlin-Frankfurt-Münster stratification for relapsed ALL. MRD was studied by real-time quantitative PCR after the first, second and third chemotherapy course (time points 1 (TP1), 2 (TP2) and 3 (TP3), respectively). MRD results, not used for treatment refinement, were categorized as negative (NEG MRD), positive not-quantifiable (POS-NQ MRD) when MRD level was below quantitative range (a level 〈10(-4)) or positive within quantitative range (POS MRD) when MRD level was 〉or=10(-4). With a median observation time of 15 months, overall 3-year event-free survival (EFS) was 27%. The 3-year EFS was 73, 45 and 19% for patients with NEG-MRD, POS NQ-MRD and POS-MRD at TP1, respectively (P〈0.05). The prognostic predictive value of MRD was statistically confirmed in multivariate analysis. MRD quantitation early and efficiently differentiates patients who benefit from conventional treatment, including allogeneic hematopoietic stem cell transplantation, from those needing innovative, experimental therapies.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Multivariate Analysis ; Predictive Value of Tests ; Recurrence ; Prognosis ; Prospective Studies ; Cytarabine - therapeutic use ; Humans ; Child, Preschool ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Methotrexate - therapeutic use ; Cyclophosphamide - therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Mercaptopurine - therapeutic use ; Female ; Neoplasm, Residual - mortality ; Asparaginase - therapeutic use ; Child ; Daunorubicin - therapeutic use ; Risk Factors ; Hematopoietic Stem Cell Transplantation ; Treatment Outcome ; Combined Modality Therapy ; Reverse Transcriptase Polymerase Chain Reaction ; Neoplasm, Residual - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Disease-Free Survival ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Neoplasm, Residual - drug therapy ; Survival Analysis ; Vincristine - therapeutic use ; Prednisone - therapeutic use ; Care and treatment ; Chemotherapy ; Leukemia in children ; Lymphocytic leukemia in children ; Stem cells ; Transplantation ; Diagnosis ; Acute lymphocytic leukemia ; Lymphoblastic leukemia in children ; Health aspects ; Cancer
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Leukemia, 2005-09, Vol.19 (9), p.1687-1689
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Leukemia-Lymphoma, Adult T-Cell - diagnosis ; Recurrence ; Leukemia-Lymphoma, Adult T-Cell - genetics ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunoglobulin Joining Region - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Immunoglobulin Variable Region - genetics ; Receptors, Antigen, T-Cell - genetics ; Child ; Sequence Analysis, DNA - methods ; Immunoglobulin Heavy Chains - genetics ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Coral reefs, 2013-09, Vol.32 (3), p.703-717
    Description: The branching coral Acropora palmata is a foundation species of Caribbean reefs that has been decimated in recent decades by anthropogenic and natural stressors. Declines in population density and genotypic diversity likely reduce successful sexual reproduction in this self-incompatible hermaphrodite and might impede recovery. We investigated variation among genotypes in larval development under thermally stressful conditions. Six two-parent crosses and three four-parent batches were reared under three temperatures and sampled over time. Fertilization rates differed widely with two-parent crosses having lower fertilization rates (5–56 %, mean 22 % ± 22 SD) than batches (from 31 to 87 %, mean 59 % ± 28 SD). Parentage analysis of larvae in batch cultures showed differences in gamete compatibility among parents, coinciding with significant variation in both sperm morphology and egg size. While all larval batches developed more rapidly at increased water temperatures, rate of progression through developmental stages varied among batches, as did swimming speed. Together, these results indicate that loss of genotypic diversity exacerbates already severe limitations in sexual reproductive success of A. palmata. Nevertheless, surviving parental genotypes produce larvae that do vary in their phenotypic response to thermal stress, with implications for adaptation, larval dispersal and population connectivity in the face of warming sea surface temperatures.
    Subject(s): Life Sciences ; Climate change ; Genotype by environment interaction ; Egg provisioning ; Freshwater & Marine Ecology ; Oceanography ; Compatibility ; Larval development ; Sperm morphology ; Fundamental and applied biological sciences. Psychology ; Sea water ecosystems ; Synecology ; Animal, plant and microbial ecology ; Exact sciences and technology ; Earth, ocean, space ; External geophysics ; Biological and medical sciences ; Climatology. Bioclimatology. Climate change ; Animal and plant ecology ; Meteorology ; Greenhouse effect ; Global temperature changes ; Reefs ; Analysis
    ISSN: 0722-4028
    E-ISSN: 1432-0975
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Heredity, 2017-08, Vol.119 (2), p.107-116
    Description: Montane environments around the globe are biodiversity 'hotspots' and important reservoirs of genetic diversity. Montane species are also typically more vulnerable to environmental change than their low-elevation counterparts due to restricted ranges and dispersal limitations. Here we focus on two abundant congeneric mayflies (Baetis bicaudatus and B. tricaudatus) from montane streams over an elevation gradient spanning 1400 m. Using single-nucleotide polymorphism genotypes, we measured population diversity and vulnerability in these two species by: (i) describing genetic diversity and population structure across elevation gradients to identify mechanisms underlying diversification; (ii) performing spatially explicit landscape analyses to identify environmental drivers of differentiation; and (iii) identifying outlier loci hypothesized to underlie adaptive divergence. Differences in the extent of population structure in these species were evident depending upon their position along the elevation gradient. Heterozygosity, effective population sizes and gene flow all declined with increasing elevation, resulting in substantial population structure in the higher elevation species (B. bicaudatus). At lower elevations, populations of both species are more genetically similar, indicating ongoing gene flow. Isolation by distance was detected at lower elevations only, whereas landscape barriers better predicted genetic distance at higher elevations. At higher elevations, dispersal was restricted due to landscape effects, resulting in greater population isolation. Our results demonstrate differentiation over small spatial scales along an elevation gradient, and highlight the importance of preserving genetic diversity in more isolated high-elevation populations.
    Subject(s): Ephemeroptera - classification ; Genetic Variation ; Genetics, Population ; Animals ; Gene Flow ; Colorado ; Genotype ; Polymorphism, Single Nucleotide ; Ephemeroptera - genetics ; Altitude ; Index Medicus ; Original
    ISSN: 0018-067X
    E-ISSN: 1365-2540
    Source: Nature Open Access
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Genetics (Austin), 2006-06-01, Vol.173 (2), p.975-983
    Description: Rice (Oryza sativa) was cultivated by Asian Neolithic farmers 〉11,000 years ago, and different cultures have selected for divergent starch qualities in the rice grain during and after the domestication process. An intron 1 splice donor site mutation of the Waxy gene is responsible for the absence of amylose in glutinous rice varieties. This mutation appears to have also played an important role in the origin of low amylose, nonglutinous temperate japonica rice varieties, which form a primary component of Northeast Asian cuisines. Waxy DNA sequence analyses indicate that the splice donor mutation is prevalent in temperate japonica rice varieties, but rare or absent in tropical japonica, indica, aus, and aromatic varieties. Sequence analysis across a 500-kb genomic region centered on Waxy reveals patterns consistent with a selective sweep in the temperate japonicas associated with the mutation. The size of the selective sweep (〉250 kb) indicates very strong selection in this region, with an inferred selection coefficient that is higher than similar estimates from maize domestication genes or wild species. These findings demonstrate that selection pressures associated with crop domestication regimes can exceed by one to two orders of magnitude those observed for genes under even strong selection in natural systems.
    Subject(s): Species Specificity ; Oryza - metabolism ; Selection, Genetic ; Genome, Plant ; Oryza - classification ; Amylose - metabolism ; Genetic Variation ; Plant Proteins - genetics ; Oryza - genetics ; Starch Synthase - genetics ; Agriculture ; Mutation ; DNA, Plant - genetics ; Evolution, Molecular ; Genetic aspects ; Research ; Nucleotide sequence ; Rice ; Index Medicus ; Investigations
    ISSN: 0016-6731
    E-ISSN: 1943-2631
    Source: PubMed Central
    Source: Genetics Society of America
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Molecular ecology, 2016-05, Vol.25 (10), p.2176-2194
    Description: The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction‐site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome‐wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential.
    Subject(s): effective population size ; divergent selection ; conservation genomics ; genetic drift ; population divergence ; Genetic Variation ; Foxes - genetics ; Genetics, Population ; Genetic Drift ; Animals ; Polymorphism, Single Nucleotide ; California ; Genotyping Techniques ; Islands ; Sequence Analysis, DNA ; Evolution, Molecular ; Animal genetics ; Genetic research ; Single nucleotide polymorphisms ; Population genetics ; Analysis ; Genomics ; Index Medicus
    ISSN: 0962-1083
    E-ISSN: 1365-294X
    Source: Smithsonian Digital Repository
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Proceedings of the National Academy of Sciences - PNAS, 2018-12-04, Vol.115 (49), p.12471-12476
    Description: Species richness is greatest in the tropics, and much of this diversity is concentrated in mountains. Janzen proposed that reduced seasonal temperature variation selects for narrower thermal tolerances and limited dispersal along tropical elevation gradients [Janzen DH (1967) 101:233–249]. These locally adapted traits should, in turn, promote reproductive isolation and higher speciation rates in tropical mountains compared with temperate ones. Here, we show that tropical and temperate montane stream insects have diverged in thermal tolerance and dispersal capacity, two key traits that are drivers of isolation in montane populations. Tropical species in each of three insect clades have markedly narrower thermal tolerances and lower dispersal than temperate species, resulting in significantly greater population divergence, higher cryptic diversity, higher tropical speciation rates, and greater accumulation of species over time. Our study also indicates that tropical montane species, with narrower thermal tolerance and reduced dispersal ability, will be especially vulnerable to rapid climate change.
    Subject(s): SEE COMMENTARY ; Temperature ; Animals ; Tropical Climate ; Genetic Speciation ; Insecta - physiology ; Animal Distribution ; Biodiversity ; Insecta - genetics ; Altitude ; Environmental aspects ; Plant populations ; Distribution ; Index Medicus ; Biological Sciences ; thermal tolerance ; climate variability ; elevation gradient ; cryptic diversity ; speciation
    ISSN: 0027-8424
    E-ISSN: 1091-6490
    Source: HighWire Press (Free Journals)
    Source: Hellenic Academic Libraries Link
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Physica scripta, 2017-12-28, Vol.93 (1), p.14001
    Subject(s): neutron sources ; superconducting linacs ; integrated control systems ; spallation targets
    ISSN: 0031-8949
    E-ISSN: 1402-4896
    Source: IOPscience extra
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  • 10
    Language: English
    In: Electrophoresis, 2011-10, Vol.32 (20), p.2830-2839
    Description: This article reports the results of a study carried out to evaluate the offline hyphenation of capillary zone electrophoresis with matrix‐assisted lased desorption ionization time of flight mass spectrometry (MALDI‐TOF‐MS) for the analysis of low‐abundant complex samples, represented by the tryptic phosphorylated peptides of phosphoproteins, such as α‐casein, β‐casein, and fetuin. The proposed method employs a latex‐coated capillary and consists in the online preconcentration of the tryptic peptides by a pH‐mediated stacking method, their separation by capillary zone electrophoresis, and subsequent deposition of the separated analytes onto a MALDI target for their MS analysis. The online preconcentration method allows loading a large sample volume (∼150 nL), which is introduced into the capillary after the hydrodynamic injection of a short plug of 1.0 M ammonium hydroxide solution and is sandwiched between two plugs of the acidic background electrolyte solution (BGE) filling the capillary. The sample spotting of the separated analytes onto the MALDI target is performed either during or postseparation using an automatic spotting device connected to the exit of the separation capillary. The proposed method allows the separation and identification of multiphosphorylated peptides from other peptides and enables their identification at femtomole level with improved efficiency compared with LC approaches hyphenated to MS.
    Subject(s): Stacking ; Phosphopeptides ; CE ; MS ; Caseins - analysis ; Amino Acid Sequence ; Limit of Detection ; Reproducibility of Results ; Molecular Weight ; Humans ; Molecular Sequence Data ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods ; Peptide Mapping - methods ; Phosphoproteins - chemistry ; Peptide Fragments - analysis ; Peptide Fragments - chemistry ; Animals ; Caseins - chemistry ; Phosphoproteins - analysis ; Cattle ; Fetuins - analysis ; Fetuins - chemistry ; Electrophoresis, Capillary - methods ; Hydrogen-Ion Concentration ; Index Medicus
    ISSN: 0173-0835
    E-ISSN: 1522-2683
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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