Clonal Evolution: The process of accumulation of genetic and epigenetic changes over time in individual cells and the effect of the changes on CELL PROLIFERATION.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Karyotyping: Mapping of the KARYOTYPE of a cell.Benzamides: BENZOIC ACID amides.Immunogenetic Phenomena: GENETIC PHENOMENA characterizing IMMUNITY and the immune response.Philadelphia Chromosome: An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).PiperazinesPhylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Chromosome Disorders: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)Leukemia, Lymphocytic, Chronic, B-Cell: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Blast Crisis: An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.Cytogenetic Analysis: Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Gene Rearrangement, B-Lymphocyte, Heavy Chain: Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Directed Molecular Evolution: The techniques used to produce molecules exhibiting properties that conform to the demands of the experimenter. These techniques combine methods of generating structural changes with methods of selection. They are also used to examine proposed mechanisms of evolution under in vitro selection conditions.Genes, abl: Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.DNA, Neoplasm: DNA present in neoplastic tissue.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell.Anemia, Aplastic: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.Genetic Variation: Genotypic differences observed among individuals in a population.Fusion Proteins, bcr-abl: Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Precursor B-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.Chromosomes, Human, Pair 8: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Comparative Genomic Hybridization: A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Recurrence: The return of a sign, symptom, or disease after a remission.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Myelodysplastic Syndromes: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Cultural Evolution: The continuous developmental process of a culture from simple to complex forms and from homogeneous to heterogeneous qualities.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Adaptation, Biological: Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.

Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. (1/77)

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Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma. (2/77)

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Psychological stress and aging: role of glucocorticoids (GCs). (3/77)

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Silencing, positive selection and parallel evolution: busy history of primate cytochromes C. (4/77)

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Somatic retrotransposition alters the genetic landscape of the human brain. (5/77)

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High order chromatin architecture shapes the landscape of chromosomal alterations in cancer. (6/77)

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Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. (7/77)

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Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms. (8/77)

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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
According to the clonal evolution model, tumour growth is driven by competing subclones in somatically evolving cancer cell populations, which gives rise to genetically heterogeneous tumours. Here we present a comparative targeted deep-sequencing approach combined with a customised statistical algorithm, called deepSNV, for detecting and quantifying subclonal single-nucleotide variants in mixed populations. We show in a rigorous experimental assessment that our approach is capable of detecting variants with frequencies as low as 1/10,000 alleles. In selected genomic loci of the TP53 and VHL genes isolated from matched tumour and normal samples of four renal cell carcinoma patients, we detect 24 variants at allele frequencies ranging from 0.0002 to 0.34. Moreover, we demonstrate how the allele frequencies of known single-nucleotide polymorphisms can be exploited to detect loss of heterozygosity. Our findings demonstrate that genomic diversity is common in renal cell carcinomas and provide ...
Conceptual revolutions have taken place in the past ten years, which have dramatically changed the field of oncology. In particular, the vast array of cancer-type diseases has emerged. The immune system has been shown to play a central role in controlling pre-cancerous cells, leading to the emergence of new areas of research. Tumoral heterogeneity, the clonal architecture of cancer cell populations, cellular plasticity, and the increasingly strong arguments on the existence of cancer-initiating stem cells have led to a different perception of tumors, no longer as monolithic, uniform cell groups, but as changing ecosystems, sensitive to the surrounding conditions and selection pressure. Stratification of cancer by omic technologies offers a new dimension, aiming to shed light on their complexity, propose and predict the validity of new therapeutic approaches, analyze and understand resistance, identify biomarkers for diagnosis, theranostics and disease progression. The ultimate Holy Grail is ...
Chris Miller is an Assistant Professor in the Division of Oncology and a member of the McDonnell Genome Institute. His focus is on developing and applying computational tools to provide insight into the origins and progression of cancer. Dr. Miller received Bachelor degrees in Biology and Computer Science from Truman State University. He received his PhD in Computational Biology from Baylor College of Medicine.. His core research interests include understanding the clonal architecture of tumors and how they evolve in response to therapy, with a special focus on hematologic cancers. His research also focuses on effective designing and targeting of cancer immunotherapies, developing open-source software for interpreting and visualizing genomic data, and integrative analysis that translates multi-dimensional genomic data into both functional and actionable contexts.. Dr. Millers Publications. Dr. Millers Website. ...
Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline polymorphisms exposed distinct somatic mutation ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
In a recent post, Philip Gerlee highlighted the two biggest contributions of mathematical oncology to cancer research: (1) increasing focus on the progress of cancer as an evolutionary process, and (2) looking at the importance of tumor heterogeneity.. For the first point, the standard historical reference is: Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23-28.. However, for the second point, although I am vaguely familiar with modern work, I dont know of a historical reference. When was tumour heterogeneity first recognized as important to cancer dynamics and treatment? Was this work related to mathematical or other modeling insights? If not, what is the first important mathematical (or computational) modeling work on tumour heterogeneity?. ...
Multistage carcinogenesis is an evolutionary process in which genetic instability generates new clones and natural selection among such variants drives clonal expansions (1, 2, 3, 4, 5, 6) . The number of genetic lesions necessary to produce a cancer is unknown for most tissues but has been variously estimated to be 2 to 12 (7, 8, 9) . Normal mutation rates in the absence of clonal expansion cannot account for the accumulation of so many lesions (10) . There has been much debate in the literature as to the relative importance of a mutator phenotype (10 , 11) and genetic instability (3 , 12) versus clonal expansion (4 , 5) in neoplastic progression.. Both genetic instability and clonal expansions are commonly observed in neoplastic progression, and it is likely that the two factors cooperate in clonal evolution (11 , 13) . If this is true, then expansion of a genetically unstable clone in a premalignant neoplasm will associate with risk of progression to cancer.. The debate over the relative ...
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Author Summary Cancer is the consequence of an evolutionary process, which lasts several decades, is impossible to observe during most of its time, and only becomes apparent in late stages. We use mathematical modeling to shed light on the evolutionary dynamics of cancer by studying the accumulation of passenger mutations. We show that the frequencies obtained by passenger mutations depend strongly on the ratio of death and birth rates of cancer cells. We use genetic data of colorectal cancer to estimate this important quantity in vivo. We estimate the size of the cancer cell population that was present when a specific mutation first emerged. Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution.
Supplementary Fig. S5 - Supplementary Fig. S5. Validation of redundant APC mutations. A, For one case (CRC2), two redundant APC mutations are validated by Sanger sequencing. One nonsense mutation (C,T; left) and one frameshift indel (AG,A; right) are shown for seven regional biopsies for the given case. For one primary case (CRC2-P1), the nonsense mutation is not observed, consistent with the metastasis-clonal presentation of this mutation. B, The copy number changes of the entire chromosome 5 are shown for seven regional biopsies. Entire loss of chromosome 5 is observed for CRC-P1. APC locus is incidated with a red dotted line ...
Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P,0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution ...
Background: PIK3CA is the single most commonly mutated gene in breast cancer, with highest incidence reported in ER positive and HER2 negative breast cancer. Substantial data now suggests that breast cancers show intra-tumoural genetic heterogeneity, with apparently clonal tumours composed of multiple populations of tumour cells that, in addition to the founder genetic events common to all cells, harbour private genetic alterations. Tumours with mutations that are sub-clonal may respond less well to therapies targeting these mutations than cancers with clonal mutations. To assess how frequently PIK3CA mutations are clonal founder mutations, or may be subclonal, we assessed the abundance on PIK3CA mutation using digital PCR.. Methods: DNA was extracted from frozen sections of 119 primary breast cancers, following macrodissection to achieve tumour cell content of ,70%. PIK3CA mutations c.1624G,A (E542K), c.1633G,A (E545K), c.3140A,T (H1047L) and c.3140A,G (H1047R) were assessed by droplet digital ...
The management of advanced colorectal cancer uses combination systemic chemotherapy with 5-fluorouracil (5-FU), irinotecan, and oxaliplatin. The EGFR-targeted agents cetuximab and panitumumab are important additions to the treatment of colorectal cancer and have demonstrated survival benefits in randomized controlled trials. However, patients cumulative exposure to drug therapy is high, with the associated toxicities and financial costs.. The concept that tumors are heterogeneous both within a single tumor lesion and between tumor lesions in the same patient (intratumor heterogeneity) has become well established over the last 30 years (1, 2). As tumors consist of diverse subclonal populations with differing genomes, epigenomes, transcriptomes, and proteomes related through a common progenitor, the capacity to evolve and develop resistance in response to selective pressures such as prolonged exposure to targeted therapies presents a significant clinical challenge.. Initial studies of acquired ...
Brady, Samuel W., Jasmine A. McQuerry, Yi Qiao, Stephen R. Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, et al. 2017. "Combating Subclonal Evolution of Resistant Cancer Phenotypes." Nature Communications 8 (1): 883. 10.1038/s41467-017-01174-3. Goldberg, Lisa R., Stacey L. Kirkpatrick, Neema Yazdani, Kimberly P. Luttik, Olga A. Lacki, R. Keith Babbs, David F. Jenkins, W. Evan Johnson, and Camron D. Bryant. 2017. "Casein Kinase 1-Epsilon Deletion Increases Mu Opioid Receptor-Dependent Behaviors and Binge Eating." Genes, Brain, and Behavior, June. 10.1111/gbb.12397. Rahman, Mumtahena†, Shelley M. MacNeil†, David F. Jenkins†, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. McQuerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson and Andrea H. Bild. 2017. "Activity of Distinct Growth Factor Receptor Network Components in Breast Tumors Uncovers Two Biologically Relevant Subtypes." Genome Medicine 9 (1): 40. 10.1186/s13073-017-0429-x. † Contributed ...
Posted: Monday, October 21, 2019. Integrating genetic, epigenetic, and transcriptional information more frequently than is already done in the clinical management of patients with chronic lymphocytic leukemia (CLL) is crucial to tailor targeted treatments in an optimized, synergic manner. Backed by an abundance of evidence, coauthors Adalgisa Condoluci, MD, and Davide Rossi, MD, both of the Oncology Institute of Southern Switzerland in Bellinzona, made their contention at the 2019 Society of Hematologic Oncology Annual Meeting in Houston (Abstract EXABS-CLL-413). Their presentation also was published in Clinical Lymphoma, Myeloma & Leukemia.. The predictive and prognostic values of some CLL biomarkers are incontrovertible, noted the authors. The "burden" of the genetic information and characteristics that technology can provide must be utilized to "follow clonal evolution and possibly avoid clonal selection conferring disease refractoriness.". CLL develops slowly, making it "a highly informative ...
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action ...
Incidence of bleeding, changes in serum thrombopoietin level, clonal evolution to PNH, clonal chromosomal population in bone marrow, myelodysplasia by morphology, or acute leukemia and health related quality of life (as measured by the Medical O ...
Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed ...
ESMO is a Swiss-registered not-for-profit organisation. All funding for this site is provided directly by ESMO or via grants from the sponsors and supporters.. Via L. Taddei 4, 6962 Viganello - Lugano - CH © Copyright 2017 European Society for Medical Oncology All rights reserved worldwide.. ...
TY - JOUR. T1 - Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines. AU - Vance, Gail H.. AU - Barry, Todd S.. AU - Bloom, Kenneth J.. AU - Fitzgibbons, Patrick L.. AU - Hicks, David G.. AU - Jenkins, Robert B.. AU - Persons, Diane L.. AU - Tubbs, Raymond R.. AU - Hammond, M. Elizabeth H.. PY - 2009/4/1. Y1 - 2009/4/1. N2 - • Context.-Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. Objectives.-To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. Design.-We convened an expert panel to discuss HER2 gene ...
Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastomas clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table ...
Study Throws Light on Mutations Facilitating Cancer Cell Survival Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. Now, with the help of this sophisticated sequencing method, researchers identified genetic mutations that promote the […]. The post Study Throws Light on Mutations Facilitating Cancer Cell Survival appeared first on BioTecNika .Read more at www.biotecnika.org/2018/03/study-throws-light-on-mutations-facilitating-cancer-cell-survival/. ...
As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of blood-based assays or "liquid biopsies" is becoming increasingly recognized in clinical practice and trial design. "Liquid biopsies" provide a less invasive approach to the current gold standard of interrogating tumors by tissue biopsies, which are frequently unfeasible, associated with morbidity, and cannot be performed as often ...
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In breast and pancreatic cancers, the majority of known mutational and copy number driver events are relatively early events [15],[16],[27],[29]. In ccRCC, however, the majority of identified driver mutations were found to be subclonal. In fact, inactivating mutations in the Von Hippel-Lindau tumor suppressor gene and loss of heterozygosity at chromosome 3p were the only somatic events occurring `early in ten ccRCC tumors analyzed [22]. Conversely, mutations in certain driver genes, including BAP1 (BRCA1 associated protein-1), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), SETD2 (SET domain containing 2) and TP53 (encoding tumor protein p53), were always subclonal, and thus probably involved in ccRCC progression. Selection for mutations in these genes during later stages of ccRCC development is evidenced by the observation that different subclones acquire mutations in the same gene in parallel.. Driver events are not ...
Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report. Abstract # 802
Most PDTCs and ATCs are thought to arise from preexisting PTCs based on their frequent co-occurrence in the same tumor specimen, where they consistently share a driver mutation (36, 40). Our results, analyzed in the context of the PTC TCGA study, provide insights into tumor microevolution and lend support to this model of tumorigenesis. Particularly compelling in this regard is the fact that mutations in the TERT promoter, which are known to activate its transcription, display a stepwise increase in frequency along the spectrum of disease progression (9% in PTCs, 40% in PDTCs, and 73% in ATCs) (1, 17-20). Interestingly, TERT mutations are subclonal in the few PTCs that harbor them, whereas they are clonal in PDTCs and ATCs, pointing to selection during tumor evolution, possibly by inducing cell immortalization. TERT promoter mutations also track with virulence of advanced disease. They are significantly associated with BRAF or RAS mutations, consistent with the proposed mechanism by which ...
The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation ...
Notably, the average size of persisting clones increased linearly with time, and their size distribution acquired long-term scaling behavior, a hallmark of a single functionally equivalent population of cells dividing at the same rate (Fig. 2C and fig. S6, A, B, and E) (18-21). Studies of interfollicular epidermis (IFE) revealed that this pattern of clonal evolution was consistent with progenitors dividing stochastically to generate differentiated and cycling daughters with equal probability (18, 19). By implementing a Bayesian inference analysis, we showed that the entire data set conforms to the IFE paradigm (Fig. 2E; fig. S6, C to E; and supplementary theory). We conclude that esophageal progenitors (EP) are functionally equivalent.. The observation of similar progenitor behavior in EE and epidermis, derived from endoderm and ectoderm, respectively, argues that squamous epithelia share a common mechanism of homeostasis irrespective of their developmental origin. However, EP behavior differs ...
Here are some very clear clips for the immune responses to infection, starting with a really well done explanation of Burnets Nobel-winning clonal selection theory: If you like that, check out some more of the videos from the Walter and Eliza Hall Institute of Medical Research. Try this animation and quiz: McGraw Hill Online Centre…
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Tasmanian devils are breeding at younger ages, and researchers at the University of Tasmania in Australia believe the phenomenon is caused by an evolutionary response to the cancer that is devastating these small marsupials.. Devil facial tumor disease (DFTD) is a contagious form of cancer that has been infecting the animals since 1996.1 Tasmanian devils are carnivorous marsupials of the family Dasyuridae. These nocturnal predators are found exclusively on the island of Tasmania and are comprised of about 50 species. They have a normal life span of five to six years, usually breeding around the ages of two or three. However, since the disease is cutting their total years down to two or three, most females would ordinarily not live to rear their first litter.. Since the onset of the epidemic, Tasmanian devils have begun to breed as early as age one. "We could be seeing evolution occurring before our eyes. Watch this space!" zoologist Menna Jones of the university said in an interview with the ...
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A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. [Cell] Full Article , Press Release , Graphical Abstract Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Mediated by a Reversible Drug-Tolerant State Barcode-mediated clonal tracking and genomic sequencing of patient-derived xenograft tumors revealed that residual tumors remaining after treatment with standard frontline chemotherapies, doxorubicin combined with cyclophosphamide, maintained the subclonal architecture of untreated tumors, yet their transcriptomes, proteomes, and histologic features were distinct from those of untreated tumors. [Sci Transl Med] Abstract , Press Release PDGFRα+ Stromal Adipocyte Progenitors Transition into ...
... s were so named for their crabby, aggressive behavior (especially around food and mating time) and the absolutely bizarre sounds that they make. They are solitary, non-monogamous, nocturnal animals, and live in burrows. Devils eat a wide variety of other creatures, though they typically only hunt things that are smaller than themselves. They also consume carrion, and thanks to their powerful teeth and jaws, are able to completely consume an animal. Devils are at their most aggressive when feeding, as it is a time that the normally solitary creatures come together and (attempt to) share a meal ...
WES of patient-matched tumor pairs from 23 individuals with HNSCC demonstrates the intertumor genetic heterogeneity of this cancer. To our knowledge, this is the first study of HNSCC to examine intertumor genetic heterogeneity in synchronous nodal metastases and metachronous recurrence across multiple patients; it provides a model to determine patterns of mutation and clonal evolution that may be targetable for the treatment of recurrent/metastatic disease.. Primary tumors in our study averaged 67.6 nonsynonymous SSNVs per tumor, including mutations in tumor suppressor genes, oncogenes, and genes that have previously been found to be significantly mutated in HNSCC, such as AJUBA, CASP8, FAT1, FBXW7, NFE2L2, and TP53 (Supplemental Table 10 and Supplemental Table 4). Interestingly, primary tumors were not found to harbor mutations in several tumor suppressor genes and oncogenes previously implicated in HNSCC, including CCND1, PIK3CA, NOTCH1, PTEN, CDKN2A, HRAS, and EGFR. However, copy number ...
Malignant melanoma is a cancer form with particularly poor response to conventional chemotherapy, but where novel immunotherapies hold great promise. We have two ongoing projects focusing on this disease: In one project, we study the clonal evolution of metastatic spread in advanced melanoma patients and assess how different metastases within the same patients are. In a second project we analyse the genetic causes behind the disease in families were individuals have a very high risk of developing melanoma at an early age.. Key publications: Birkeland, E., Zhang, S., Poduval, D., Geisler, J., Nakken, S., Vodak, D., Meza-Zepeda, L.A., Hovig, E., Myklebost, O., Knappskog, S., Lønning P.E. (2018) Patterns of genomic evolution in advanced melanoma. Nature Communications. Provisionally accepted. ...
Australian scientists said on Thursday they had made a breakthrough in the fight to save the cancer-hit Tasmanian devil by mapping the species genome for the first time.
The Tasmanian devil, another iconic animal of Tasmania, is now the islands largest surviving carnivorous marsupial. It is known for its powerful jaws and scream-like vocalizations. Tasmanian devils are also unique because they suffer from devil facial tumor disease - an infectious, non-viral parasitic cancer which they can transmit to one another through fighting. While the unusual disease makes the animals of interest to cancer researchers, it is threatening the survival of the remaining Tasmanian devils, whose wild population has declined by 70 percent during the past 20 years ...
The former chief of Eli Lilly USA is picked to replace Tom Price, who stepped down in September amid a controversy over the abuse of taxpayer-funded travel.. 0 Comments. ...
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been
The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.
The outcome of patients with MM has improved substantially during the last decades as a result of drug development and progress in the understanding of disease biology.11,12 However, even in the era of novel agents some patients with high-risk cytogenetic abnormalities or early relapse after first-line treatment have a dismal outcome.13,14 Clonal heterogeneity and evolution are contributors to disease progression and ultimately refractoriness in MM.6 So far, there are only limited data available that proved clonal evolution in patients relapsing after ASCT for newly diagnosed disease. With our current analysis of 128 patients with FISH data at primary diagnosis and relapse after ASCT we demonstrate that high-risk cytogenetic abnormalities occur more frequently at relapse. This observation was especially due to de novo gains of chromosome 1q and new deletions of chromosome 17p. No changes were observed between primary diagnosis and relapse for defined IGH translocations, including t(4;14).. A ...
Researchers believe the milk of the Tasmanian devil can hold the key to fighting drug-resistant bacteria. This milk builds a strong immune system that protects the joeys from infection and pathogens.
The Tasmanian Devil is afflicted by a unique type of contagious cancer that s never been seen in nature before Unless the spread of the cancer can be stopped the Devils could be wiped out with devas
Something extraordinary is evolving among the feisty inhabitants of the remote north-west coast of Tasmania. Something thats both astounding and delighting the researchers monitoring them. For more than 20 years, these apple-isle locals have been suffering an ugly cancer thats caused population numbers to rapidly decline. The problem has raised many complex questions and stirred urgent…
The Tasmanian Department of Primary Industries, Parks, Water and Environment (DPIPWE) is seeking comments on the strategies, objectives and recovery actions outlined in the Draft Tasmanian Devil Recovery Plan. Comments must be received by 11 February 2011. read more... ...
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The Tasmanian devil (Sarcophilus harrisii) is the worlds largest surviving marsupial carnivore. The devil facial tumour disease (DFTD) is currently threatening Tasmanian devils with extinction. Since its emergence around 1996, the disease has spread rapidly across the state resulting in a population decline of around 80 % [1]. This had led to Tasmanian devils being listed as endangered by the International Union for Conservation of Nature (IUCN) [2]. An unusual feature of DFTD is that it is transmitted as an allograft when Tasmanian devils bite each other [3, 4]. This makes DFTD one of only three naturally occurring clonally transmissible tumours along with canine transmissible venereal tumour in dogs [5], and a recently identified transmissible cancer in clams [6]. This tumour is able to transmit between unrelated hosts without eliciting an immune response [7, 8], but how this tumour avoids the host immune system is not fully understood. The tumour down-regulates cell surface Major ...
Cancer arises from accumulation of somatic mutations and accompanying evolutionary selection for growth advantage. During the evolutionary process, an ancestor clone branches into multiple clones, yielding intratumor heterogeneity. However, principles underlying intratumor heterogeneity have been poorly understood. Here, to explore the principles, we built a cellular automaton model, termed the BEP model, which can reproduce the branching cancer evolution in silico. We then extensively searched for conditions leading to high intratumor heterogeneity by performing simulations with various parameter settings on a supercomputer. Our result suggests that multiple driver genes of moderate strength can shape subclonal structures by positive natural selection. Moreover, we found that high mutation rate and a stem cell hierarchy can contribute to extremely high intratumor heterogeneity, which is characterized by fractal patterns, through neutral evolution. Collectively, This study identified the ...
A week or so ago, Ann Maree Pearce, a government cytogeneticist from Australias island state, Tasmania, and colleagues said in a Nature news report that a nasty facial cancer affecting the Tasmanian devil population, dubbed Devil Facial Tumour Disease, was in fact an infective cell line being passed between the ferocious, foxed-sized scavengers via bites and so on. At the linkurl:18th Lorne Cancer Conference Erskine on the Beach;http://www.the-scientist.com/blog/display/23110/ in Lorne, Austra
Since cancer shares the same molecular machinery as the host, most therapeutic interventions which aim to target cancer would inadvertently also adversely affect the host. Additionally, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation suggests that the evolution of cancer, usually seen as a major clinical challenge, may also afford a key opportunity in lowering on-target toxicities accosted with chemotherapy. As an
The liver CSC concept has been acknowledged to explain the molecular diversity of malignant phenotypes in liver cancer. However, many questions remain, including the role of hepatitis viruses, the origin of liver CSCs, the existence and role of the stem cell niche, similarities and differences between normal hepatic stem/progenitor cells and liver CSCs, the timing of CSC emergence, CSC concept universality in liver cancers, and the relationship between CSC plasticity and clonal evolution accompanied by genetic and epigenetic changes (11). Although chronic HBV and HCV infections are two major risk factors for the development of liver cancer, their roles in liver CSCs are largely unknown. It is also unclear whether HBV and HCV infect and replicate in hepatic stem/progenitor cells, but a recent study suggested that HCV could replicate in human fetal hepatocytes (132). Clinicopathological analysis of surgically resected HCC specimens suggested that EpCAM+ CSCs were more frequently detected in HBV- ...
Urothelial carcinomas are frequently multicentric, occurring at multiple separate sites within the urinary tract (4, 5). Urothelial tumor multifocality is often present before the onset of clinical symptoms (3), and patients with multiple, separate tumors are at higher risk for recurrence, progression, and cancer-related death (4, 5, 44). Although numerous studies have been done to address the clonal nature of multifocal urothelial carcinoma, no consensus currently exists on whether these lesions are monoclonal in origin or whether they arise independently. Two explanations have been proposed to explain tumor multifocality within the urothelium: the monoclonal theory and the "field-effect" theory. Whereas the two theories are not mutually exclusive, it is unknown which mechanism is more important in leading to urothelial tumor multifocality. Detailed characterization and comparison of genetic alterations in the cells of separate tumors may provide information about the clonal evolution of ...
Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research Nat Prod Rep. 2019 01 01; 36(1):248-249. . View in PubMed. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research Nat Prod Rep. 2019 01 01; 36(1):35-107. . View in PubMed. Rare Pediatric Invasive Gliofibroma Has BRAFV600E Mutation and Transiently Responds to Targeted Therapy Before Progressive Clonal Evolution JCO Precis Oncol. 2019; 3. . View in PubMed. Noninvasive estimation of fetal lung maturity with magnetic resonance spectroscopy Am J Obstet Gynecol. 2018 08; 219(2):209-210. . View in PubMed. Association between Subcortical Morphology and Cerebral White Matter Energy Metabolism in Neonates with Congenital Heart Disease Sci Rep. 2018 09 19; 8(1):14057. . View in PubMed. Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart DiseaseJ Pediatr. 2017 04; ...
The devil is apparently in the chromosomes.. In 1996 there were approximately 250,000 Tasmanian devils (Sarcophilus harrisii) in the wild, but by 2009 their numbers had crashed to less than 50,000 - some populations decreased by 90 per cent. The cause: the infamous Devil Facial Tumour Disease (DFTD), a transmissible cancer that has now decimated 85 per cent of Tasmanian devils in the wild.. It is estimated that over 100,000 animals have died from this unsightly disease and, despite all our hopes, its not showing any signs of slowing down. In fact, new research from the University of Sydney (USYD) suggests that this disease is able to survive indefinitely and could possibly get stronger in the future.. These hopes werent completely unfounded, the disease has been out there among the devils for 16 years and has divided millions of times, according to USYD postdoctoral research fellow Beata Ujvari. The low genetic material allows the disease to spread between individuals - its one of only three ...
Tasmanian devils have highly complex and ancient immunoglobulin light chain variable repertoires. Our article with Kathy Belov just gone online. Check out: http://www.sciencedirect.com/science/article/pii/S0165242715001750
Blue Eyed Devil lyrics by Soul Coughing: (M. Doughty) / Blue eyed devil. / Blue eyed devil. / Born to be a God among Salesmen. / Working
DEVIL: Oh, come on. Im sure its no news flash to you that I hardly have to go recruiting. My friend, you must be aware of how many come to us from up here, practically begging for a change of scenery. Listen, far be it from me to tell you how to run your paradise, but have you ever thought that installing a jacuzzi or two up here might not be the worst idea in the world? A place to go dancing, maybe? A pool table? Again, its none of my business - but it may not be in your very best interest to keep everything up here so constant.. GOD: Oh, right. And maybe we can just turn those jacuzzis up to about a million degrees, huh? Ill tell you what, "friend": you worry about your domain, and Ill worry about mine. Im doing fine, thank you very much.. DEVIL: No argument here. I know you do very well indeed. And I certainly did not mean to imply that you are anything less than the end all and be all of all that ever was or could ever be. (Wistfully.) I can only dream of obtain-ing such influence ...
Devil To Pay is the second nove, chronologically, but the first in order of publication, in the Richard Delancey series by C. Northcote Parkinson. Parkinson is best known for his work in the field of public administration and is credited with the eponymous Parkinsons Law or Work expands so as to fill the time available…
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Strong northeast winds have muddied water. Most productive perch fishermen have been at the end of piers in Burnham Harbor jigging Swedish Pimples, Jig-A-Whopper and Jigging Rapalas in 12 to 16 feet
A better understanding of P. infestans population dynamics will contribute to more durable disease management strategies, particularly if high-resolution neutral markers are combined with the use of functional markers, for example, for virulence toward individual R genes. Here, we analyzed the Dutch P. infestans population over an entire decade, determined the overall population structure, and described the emergence, dynamics, and displacement of the main clonal lineages in correlation with regional cultural practices.. STRUCTURE analysis using a set of 12 highly informative SSR markers splits the Dutch P. infestans population into three major clusters, which for Cluster 2, roughly corresponds to the NE geographical region of origin. Cluster 1 consists of a single clonal lineage, NL-001, with 27 subclones previously identified as genotype "Blue_13" (Lees et al. 2009). The subclonal lineages showed small but consistent differences, mostly by loss of alleles and by the presence of rare alleles in ...
Lachish, S and Jones, ME and McCallum, HI (2007) The impact of disease on the survival and population growth rate of the Tasmanian devil. Journal of Animal Ecology, 76. pp. 926-936. ISSN 0021-8790 ...
Definition of blue devil in the online dictionary, Lexipedia. The meaning of blue devil. What does blue devil mean? blue devil synonyms, blue devil antonyms. Information about blue devil in the free online dictionary and thesaurus.
The Devil You Know has 4,171 ratings and 145 reviews. Julie (jjmachshev) said: Whew! Im almost at a loss for words. The Devil You Know is book 2 in Je...
Devil Fruits Devil Fruits are mystical fruits found in the world that can give the eater many different and varying kinds of strange and interesting abilities,
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The Devils celebrate following a second-period goal by defenseman Anton Volchenkov (not pictured) that was deflected into the net off Kings defenseman Slava Voynov (not pictured) during Game 1 of the Stanley Cup Final.
PVP Tienda: 7.95€ / P.V.P Web: 7.55€ Serie: Defense Devil Autor: Youn In-Wan / Yang Kyung-Il Editorial: Panini Páginas: 206 páginas B/N Idioma: Castellano 
... Basic Rules Any member can roll for a fruit, no matter what kind of progress was made. Members can be just starting out and still be able to tr
Cowpokes on Devils Thumb Ranch | We didnt forget our little wranglers. All childrens treatments are booked in a couples treatment room with a parent…
Zoldan, K. et al. Automated clonal selection of high-producing hybridoma colonies from methylcellulose-based, semi-solid medium using the cell separation robot CellCelectorTM nature methods application notes 2010 ...
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12/29/15: David Schlemko fires a wrister from the corner that redirects off Justin Faulk, beating Cam Ward to give the Devils a 3-2 lead late
It turns out that marsupials do not just make more genes for cathelicidin proteins, they also make more potent ones. Two cathelicidin proteins from the tammar wallaby (Macropus eugenii) were able to kill two different antibiotic-resistant bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa) [1].. A team of Australian researchers argued the Tasmanian devils may have an even greater need than wallabies for strong, broad-spectrum antimicrobials [1]. Offspring are born after only 30 days of gestation and weigh only 0.3 grams [1]. To get an idea of just how small this is, a paper clip weighs around 1 gram. Add to this highly altricial start the observation that Tasmanian devils lead a very aggressive lifestyle (they are not called devils for nothing), resulting in cuts and bites that require pathogen protection. If the calm tammar wallaby makes such potent proteins, what about the truculent Tasmanian devil?. To address this question, researchers Emma Peel and her colleagues began by searching ...
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Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor ...
Using quantitative clonal strategies, we confirmed that RSCs are located at the peripheral extremity of the CMZ, which functions as a stem cell niche (Raymond et al., 2006; Xue and Harris, 2012), where they divide mainly in the radial orientation promoting asymmetric fate outcome and ensuring a constant production of RPCs. We also show that the same simple model (using the same parameters) that was shown to describe the clonal evolution in embryonic RPCs (He et al., 2012) fits the proliferative statistics of RPCs in the CMZ, suggesting the functional equivalency of the embryonic and CMZ progenitor cells.. The location of RSCs at the extreme periphery of the CMZ is consistent with previous studies based on molecular markers and label retention (Ahmad et al., 2004; Johns, 1977; Ohnuma et al., 2002; Xue and Harris, 2012). The position of RSCs in the CMZ, with access to the apical epithelial surface and close association with the ring blood vessel, is a feature that is common to other neurogenic ...
In the same way, the Thorny Devil "sucks up" water. So, if the Thorny Devil wants a drink, it can simply step in water and suck up the entire puddle and bring the water to its mouth with the tiny channels on its skin. It never even has to put its mouth in the water. This ability keeps the lizard alive, because any dew or moisture on plants or in the sand can be taken into its body this way.. Also, God gave the Thorny Devil several interesting ways to defend itself. Of course, the most obvious defensive tool of the Thorny Devil is its spiky skin. Just think, if you were a predator, would you want to eat something that looks like a pincushion, full of sharp spikes? Me neither. In addition to its spikes, the Thorny Devil has a "false head" on its neck just behind his real head. This false head is large and spiky. When the Thorny Devil is threatened, it can lower its real head between its front two legs and raise its "false head" to look like a head. By doing this, it protects its vital, important ...
Lyrics to Heart Of The Devil by Danzig: I am / Heart / Of the devil / I have / Heart / Of the / Devil / I can make a man / Freeze in his
Lennie Roberts, the original protagonist for the Devils Slide tunnel, drills the symbolic first hole as excavation begins on the south portal of the Devils Slide Tunnel, which will speed the trip from San Francisco to Half Moon Bay ...
The cancer, which causes genital tumors in dogs and is spread by sexual contact, is 11,000 years old. By Marc Silver National Geographic Canines are in a rare category when it comes to cancer: They and Tasmanian devils are the only two animals that can transmit it from one individual to another. A new genetic study…
Brock Lesnar: The champ erased any doubt about the legitimacy of his title reign when he methodically pounded out former conqueror Mir in two rounds at UFC 100 back in July. Lesnars game plan, which he executed masterfully, showed his tremendous improvement as a fighter since the first time the pair squared off. Rather than come out like an angry Tasmanian Devil with instant takedowns and wild ground-and-pound attacks, the champ executed a takedown, expertly moved into side control during the transition, took his time to make sure that he had the proper position, and then unloaded the most devastating series of arm punches in UFC history in a way that left him wholly unexposed to submission attempts or sweeps. It was as dominant of a performance as we have seen in the heavyweight division in quite a long time. Now that Lesnar is back in training following his bout with that pesky little bacteria, he finally has what appears to be a clear number one contender in undefeated Mexican-American ...
He hopes to remain with the New Jersey Devils long-term, he said. The fact that he is playing on a one-year contract had more do with circumstances than calculation.
Devil May Cry 3: Dantes Awakening PlayStation 2 walkthrough and guide at GameSpy - Check out the latest walkthroughs and guides for PlayStation 2
/wp-content/uploads/2011/06/castlevania.jpg!!!;!!!Castlevania, known as Akumajō Dracula (悪魔城ドラキュラ Akumajō Dorakyura, lit. Devils Castle Dracula) in Japan, is a
Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in
Advances in hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have improved survival in severe aplastic anemia (SAA) from 10%-20% in the 1960s to 80%-90% today. A matched sibling HSCT is the treatment of choice in younger patients, whereas IST is often used in older patients or in those who lack a histocompatible sibling. Graft rejection, GVHD, and poor immune reconstitution (with associated infectious complications) limit the success of HSCT, whereas lack of response, relapse, and clonal evolution limit the success of IST.
The Ope Ope no Mi is a Paramecia-type Devil Fruit that allows its user to create a the effect will result as a normal cut, as seen when the SAD gushed out of the . Despite the ROOM being stationary, in both One Piece: Gigant Battle 2 and Missing: leathers. The Artificial Devil Fruit is a type of Devil Fruit created by scientific means, as he was barely big enough to carry Monkey D. Luffy, a normal-sized human. A few Missing: leathers. Im talking about experience here as a anime fan, not a One Piece fan. I know that there can only be one devil fruit at a time but has Oda actually said and it doesnt prove how grammatically correct it is, but it certainly rolls off the tongue better. . I think they onky became standard because of laws on health and safety nd ...
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In this paper we present a new kind of vortex lenses in which the radial phase distribution is characterized by the "devils staircase" function. The focusing properties of these fractal DOEs coined Devils vortex-lenses are analytically studied and the influence of the topological charge is investigated. It is shown that under monochromatic illumination a vortex devils lens give rise a focal volume containing a delimited chain of vortices that are axially distributed according to the self-similarity of the lens.. ©2009 Optical Society of America. Full Article , PDF Article ...
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Devils Pact: Less than Perfect. Kyburi was disappointed that she hadnt been able to rattle Agura to the point where shed be reduced to a quivering wreck - her life would have been so much easier if that had happened. Those sorts were more willing to give up their secrets than the Human female, whom she had a sort of respect for. There were few beings in the Multiverse that could have the mentality of an icicle when they where inches from death at her claws, not counting the other members of the Red Sentient 5, and even fewer of those had the audacity to insult her under such circumstances. Agura was one of those beings.. The point remained - the Red Sentient female had no intention of fighting Agura down here, where the rock jammed her comm. and positioning devices, making it impossible to alert Krytus of her position. Better to do it aboveground, where the RS5 could join her in subduing the driver of the green, inferior vehicle that was so similar to the Venikus.. Green. Sun and stars, why ...
Ilya Kovalchuk will not play for the Devils in either game of a home-and-home set against the Capitals this weekend, NorthJersey.com reports. Kovalchuk has not...
Tony Scott made a short film called Beat the Devil. Hes gone, but he left us this interesting film to remember him by. It stars James Brown, Clive Owen, Gary Oldman and Marilyn Manson. ...
Clonal evolution[edit]. Main article: Somatic evolution in cancer. Just like a population of animals undergoes evolution, an ... Clonal evolution[edit]. Main article: Somatic evolution in cancer. While genetic and epigenetic alterations in tumor suppressor ... the process of carcinogenesis is formally a process of Darwinian evolution, known as somatic or clonal evolution.[60] ... Nowell PC (October 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260): 23-8. Bibcode:1976Sci...194... ...
Loxdale, H.D. & Lushai, G. (2003) Maintenance of aphid clonal lineages: images of immortality. Infection, Genetics & Evolution ... Loxdale, H.D. & Lushai, G. (2003) Rapid changes in clonal lines: the death of a 'sacred cow'. Biological Journal of the Linnean ... Loxdale, H.D. (2009) What's in a clone: the rapid evolution of aphid asexual lineages in relation to geography, host plant ... Lushai, G., Loxdale, H.D. & Allen, J. A. (2003) The dynamic clonal genome and its adaptive potential. Biological Journal of the ...
... better known as the somatic evolution model. The clonal evolution model, which occurs in both the CSC model and stochastic ... 4). These two models are not mutually exclusive, as CSCs themselves undergo clonal evolution. Thus, the secondary more dominant ... Nowell, PC (October 1, 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260): 23-8. Bibcode:1976Sci... ... Cancer Stem Cells versus Clonal Evolution". Cell Press. 138 (5): 822-9. doi:10.1016/j.cell.2009.08.017. PMID 19737509. Wang W, ...
The clonal evolution model was first proposed in 1976 by Peter Nowell. In this model, tumours arise from a single mutated cell ... These are the cancer stem cell model and the clonal evolution model. The models are not mutually exclusive, and it is believed ... Stem cell variability is often caused by epigenetic changes, but can also result from clonal evolution of the CSC population ... This has been suggested as a reliable method for tracking clonal evolution. However, this technique proves challenging in ...
... termed clonal evolution, drives progression towards more invasive stages. Clonal evolution leads to intra-tumour heterogeneity ... Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (August 2006). "Clonal origin and evolution of a transmissible cancer". ... This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the ... Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal ...
"Clonal origin and evolution of a transmissible cancer". Cell. 126 (3): 477-487. doi:10.1016/j.cell.2006.05.051. PMC 2593932 . ... Rebbeck, CA; Thomas, R; Breen, M; Leroi, AM; Burt, A (September 2009). "Origins and evolution of a transmissible cancer". ... Michael J. Metzger, Carol Reinisch, James Sherry, Stephen P. Goff (2015). "Horizontal transmission of clonal cancer cells ... Evolution. 63 (9): 2340-9. doi:10.1111/j.1558-5646.2009.00724.x. PMID 19453727. Strakova, A; Murchison, EP (February 2015). " ...
doi: 10.1016/j.gde.2015.03.005 Murgia, C; Pritchard JK; Kim SY; Fassati A; Weiss RA (2006-08-11). "Clonal Origin and Evolution ... Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A (2009). "Origins and Evolution of a Transmissible Cancer". Evolution. 63 (9): ... The infectious agent of canine transmissible venereal tumor is the cancer cell itself and the tumor is clonal in origin. All ...
Clonal origin and evolution of a transmissible cancer. Cell. 2006 Aug 11;126(3):477-87. Rayaa, G. et al. 2002. The Use of ...
Given this insignificant level of clonal mixing, there is a low chance for barriers to the evolution and propagation of an ... the researchers were able to examine the degree of clonal mixing in the colony. Clonal mixing is defined as the "mixing" of ... Ecology of Social Evolution. Davies, John R. Krebs, Stuart A. West, Nicholas B. (1981). An Introduction to Behavioural Ecology ... So, the researchers concluded that the aphids do not adapt to short-term changes in the colony via a reduction of clonal mixing ...
All ambrosia fungi are probably asexual and clonal. Mueller, U. G., N. M. Gerardo, et al. (2005): The Evolution of Agriculture ...
... termed clonal evolution, drives progression towards more invasive stages.[76] Clonal evolution leads to intra-tumour ... "Clonal origin and evolution of a transmissible cancer". Cell. 126 (3): 477-87. doi:10.1016/j.cell.2006.05.051. PMC 2593932. ... This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the ... Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal ...
Clonal origin and evolution of a transmissible cancer. Cell. 2006 Aug 11;126(3):477-87. ...
"Moving Toward a Clonal Man: Is This What We Want?" The Atlantic Monthly (1971). Park, Alice (April 17, 2014). "Researchers ... Lederberg Joshua (1966). "Experimental Genetics and Human Evolution". The American Naturalist. 100 (915): 519-531. doi:10.1086/ ... Sims Bainbridge, William (October 2003). "Religious Opposition to Cloning". Journal of Evolution and Technology. 13. [permanent ... "Moving Toward the Clonal Man", in 1971. With the cloning of a sheep known as Dolly in 1996 by somatic cell nuclear transfer ( ...
January 2012). "Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing". Nature. 481 (7382). ... A big contribution to cancer death and failed cancer treatment is clonal evolution at the cytogenetic level, for example as ... 2010). "Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors". Genome Biology. 11 (8): R82. ... October 2009). "Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution". Nature. 461 (7265). ...
Clonal selection theory Major histocompatibility complex (MHC) Tissue typing Transplant rejection "Histocompatibility". ... Kasahara, M. (2000). Major Histocompatibility Complex: Evolution, Structure, and Function. New York: Springer. ISBN 978-4-431- ...
McGovern, Tamara N. (2002). "Sex-ratio bias and clonal reproduction in the brittle star Ophiactis savignyi". Evolution. 56 (3 ...
"Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. 2 (3): 567-573. doi: ... March 2015). "Convergent evolution of the genomes of marine mammals". Nature Genetics. 47 (3): 272-5. doi:10.1038/ng.3198. PMID ... November 2007). "Evolution of genes and genomes on the Drosophila phylogeny". Nature. 450 (7167): 203-18. Bibcode:2007Natur.450 ... Genomic basis for the convergent evolution of electric organs". Science. 344 (6191): 1522-5. doi:10.1126/science.1254432. PMID ...
"Clonal genome evolution and rapid invasive spread of the marbled crayfish". Nature Ecology & Evolution. doi:10.1038/s41559-018- ... Günter Vogt (2010). "Suitability of the clonal marbled crayfish for biogerontological research: A review and perspective, with ... Development Genes and Evolution. 216 (4): 169-184. doi:10.1007/s00427-005-0041-8.. ...
Evolution, 3rd edition. Blackwell Publishing, p. 314. John Maynard Smith The Evolution of Sex 1978. Halliday, Tim R.; Adler, ... clonal plant". Ecology. 81 (2): 532-542. doi:10.1890/0012-9658(2000)081[0532:coaagt]2.0.co;2. "Timeline of same-sex procreation ... The evolution of sexual reproduction is a major puzzle for biologists. The two-fold cost of sexual reproduction is that only 50 ... "Recombination and the Evolution of Diploidy". Genetics. Vol 131 (1992): 745-751. Bernstein H, Hopf FA, Michod RE. (1987) The ...
... clonal evolution or a phenotypic mimic?". Hum. Pathol. 32 (10): 1102-8. doi:10.1053/hupa.2001.28252. PMID 11679945. Itakura E, ... will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically ...
"Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer". Cancer ... This explains the concept of tumour heterogeneity and the order of genetic events during tumor evolution. Many of the genes ... The genetic profiles of primary and metastatic lesions in breast carcinomas show a large extent of clonal pertinence between ... "Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution". Nature. 461 (7265): 809-13. doi: ...
Clonal species like the New Zealand mudsnail can often develop clonal lines with quite diverse appearances, called morphs. ... Evolution. 50 (4): 1541-1548 Schreiber, E. S. G., A. Glaister, G. P. Quinn and P. S. Lake. 1998. Life history and population ... However, asexual offspring are clonal, so lack variation. This makes them susceptible to parasites, as the entire clonal ... Clonal variation in life-history traits and feeding rates in the gastropod, Potamopyrgus antipodarum: performance across a ...
In a broad academic audience, the concept of the evolution of the genetic code from the original and ambiguous genetic code to ... de Visser JA, Rozen DE (Apr 2006). "Clonal interference and the periodic selection of new beneficial mutations in Escherichia ... As an example for addressing stop codon evolution, it has been suggested that the stop codons are such that they are most ... Later during evolution, this matching was gradually replaced with matching by aminoacyl-tRNA synthetases. Optimality: the ...
"Complex spatial clonal structure in the macroalgae Fucus radicans with both sexual and asexual recruitment". Ecology and ... Evolution. 5 (19): 4233-4245. doi:10.1002/ece3.1629. ISSN 2045-7758. PMC 4667831 . PMID 26664675. "BAMBI, Baltic Sea Marine ...
Repeated evolution of theft in fungus farming ambrosia beetles. Evolution, 64 (11): 3205-3212 Paine, T. D., K. F. Raffa, et al ... All ambrosia fungi are probably asexual and clonal. Some beetles are known to acquire ("steal") fungal inoculum from fungal ... 2001): The evolution of agriculture in beetles (Curculionidae: Scolytinae and Platypodinae). Evolution 55: 2011-2027. Malloch, ... During their evolution, most scolytid and platypodid weevils became progressively more or less dependent on fungi regularly co- ...
... clonal interference, antibiotic resistance, the evolution of novel traits, and speciation. He is also well known for his ... coli long-term evolution experiment is an ongoing study in experimental evolution led by Richard Lenski that has been tracking ... coli Long-term Experimental evolution site BEACON Center for the Study of Evolution in Action News release from Michigan State ... One particularly striking adaptation was the evolution of a strain of E. coli that was able to use citrate as a carbon source ...
... decreases impaired proliferation in response to antigenic stimulation the accumulation and the clonal expansion of memory and ... and harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution ...
Maddamsetti, Rohan; Lenski, Richard E.; Barrick, Jeffrey E. (2015). "Adaptation, Clonal Interference, and Frequency Dependent ... Interactions in a Long Term Evolution Experiment with Escherichia coli". Genetics. 200 (2): 619-631. doi:10.1534/genetics. ...
The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by ...
a) Branching clonal architecture of clonal evolution in cancer. Selective pressures allow some mutant sub-clones to expand ... Divergent (branching) clonal evolution of cancer with topographical separation.. In each example, a clonal (single cell) ... Clonal evolution in cancer.. Greaves M1, Maley CC.. Author information. 1. Division of Molecular Pathology, The Institute of ... Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive ...
Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of ... Breast tumor heterogeneity: cancer stem cells or clonal evolution?. Campbell LL1, Polyak K. ... suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor ...
Landscape of somatic mutations and clonal evolution in mantle cell lymphoma Message Subject (Your Name) has sent you a message ... Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Sílvia Beà, Rafael Valdés-Mas, Alba Navarro, ... Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our ...
Researchers sequenced samples from hundreds of individuals with aplastic anemia to narrow in on somatic mutation and clonal ... Sequencing Offers Clues to Clonal Evolution in Aplastic Anemia. Jul 02, 2015 ... Evolution of Tumor Profiling in a Clinical Lab: Moving toward Comprehensive Genomic Profiling. ... researchers from the US and Japan described mutation and clonal dynamic patterns in aplastic anemia - a non-cancerous condition ...
It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patients cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.. ...
This evidence, along with models of clonal interference (1-4), allows certain properties of the adaptive evolution of RNA ... suggests that clonal interference may play an important role in their adaptive evolution. Our goal here is to infer the ... The clonal interference model used to estimate μb andE(s) makes two important assumptions. The first is that selection ... The model of clonal interference (4) has the additional advantage of allowing us to estimate the beneficial mutation rate (μb) ...
Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. Koichi ... Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia ... These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution ... supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. ...
Exome, Targeted Sequencing of Biopsy, ctDNA Reveals Clonal Evolution of Breast Cancer Tumors. Nov 16, 2015 ... Home » Exome, Targeted Sequencing of Biopsy, ctDNA Reveals Clonal Evolution of Breast Cancer Tumors ... tumor DNA to characterize the genomic architecture of a breast cancer patients tumor and track its clonal evolution over time ...
Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the ... Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. Ugo Testa * , Germana ... Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the ... Testa U, Castelli G, Pelosi E. Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem ...
Origins and clonal evolution of childhood leukaemia. Add to your list(s) Download to your calendar using vCal ... University of Cambridge , Talks.cam , Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer , Origins and clonal ... Overall, our studies suggest that clonal selection in leukaemia results from the combined influence of genetic and epigenetic ...
Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution. ...
Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells. ... "Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells ... Clonal Evolution and Tumor-Initiating Cells. Med. Sci. 2018, 6, 31. ... Clonal Evolution and Tumor-Initiating Cells. Medical Sciences. 2018; 6(2):31. ...
Fifteen patients had clonal evolution alone (AP-CE), 32 had AP features but no evidence of clonal evolution (HEM-AP), and 24 ... and a third group had accelerated phase features plus clonal evolution (HEM-AP + CE, n = 24) (Table4). Clonal evolution ... The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Michael E. ODwyer, Michael ... The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood, 100(5), 1628-1633. ...
Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ... Chromothripsis-Mediated Structural Variations and Clonal Evolution In Recurrent Childhood High Hyperdiploid Acute Lymphoblastic ...
Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Message Subject (Your Name) has sent you a message from ...
Progression of malignant tumors is largely due to clonal evolution of the primary tumor, clones acquiring different sets of ... Progression of malignant tumors is largely due to clonal evolution of the primary tumor, clones acquiring different sets of ... Prostate cancer (PCa) provides an illustrative example of clinically significant clonal evolution. The review considers the ... Hormone Resistance and Neuroendocrine Differentiation Due to Accumulation of Genetic Lesions during Clonal Evolution of ...
Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia. Authors. MALČÍKOVÁ ... Using ultra-deep next-generation sequencing (NGS), we performed a detailed analysis of TP53 mutations clonal evolution. We ... Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia ...
Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ... Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children ...
Clonal Evolution in Aplastic Anemia is Driven by Chromosomal Instability Rather than Mutations in Myeloid Malignancy Candidate ...
Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy. Hubing Shi, Willy Hugo, Xiangju Kong, ... Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy Message Subject (Your Name) has forwarded a ...
To our knowledge, this is the first report of clonal evolution involving chromosome 5 occurring during the evolution of MDS ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ...
Evolution" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications ... Incidence of disease correlated with Daphnia clonal turnover*, ... The clonal make‐up and turnover of the Daphnia host population ... Clonal diversity, clonal persistence and rapid taxon replacement in natural populations of species and hybrids of the Daphnia ... Copyright © 2018, Society for the Study of Evolution. ISSN. 0014-3820. eISSN. 1558-5646. D.O.I.. 10.1111/evo.13413. Publisher ...
Purpose: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been ... CE, clonal evolution model; PE, parallel evolution model; SG, same-gene model. ... According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is ... Clonal and Parallel Evolution of Primary Lung Cancers and Their Metastases Revealed by Molecular Dissection of Cancer Cells. ...
  • Comparative analysis with 923 GBS genomes belonging to CC1, CC19, and CC23 revealed that the evolution of CC17 is distinct from that of other human-adapted lineages and recurrently targets functions related to nucleotide and amino acid metabolism, cell adhesion, regulation, and immune evasion. (asm.org)
  • Co-evolution of the outer surface protein C gene (ospC) and intraspecific lineages of Borrelia burgdorferi sensu stricto in the northeastern United States. (cdc.gov)
  • A key focus is on the identification of clonal lineages of B-cells undergoing the process of somatic hypermutation in germinal centres and the maturation pathways by which these lineages develop over time. (hindawi.com)
  • However, genetic data have shown the AIDS-associated pathogen Penicillium marneffei to have extensive spatial genetic structure at local and regional scales, and although there has been some genetic evidence that a sexual cycle is possible, this haploid fungus is thought to be genetically, as well as morphologically, asexual in nature because of its highly clonal population structure. (plos.org)
  • During the Chilean epidemic, the pandemic strain consisted of a highly clonal population [ 8 ], which reproduced extensively in the Chilean shore lines, and shared its habitat with many other related species. (biomedcentral.com)
  • In chronic myelogenous leukemia (CML), the development of chromosomal abnormalities in addition to the Philadelphia chromosome (clonal evolution) is considered by many to be a feature of accelerated phase (AP). (bloodjournal.org)
  • Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by a specific chromosomal translocation, t(9;22), resulting in a shortened chromosome 22, commonly referred to as the Philadelphia (Ph) chromosome. (bloodjournal.org)
  • Examination of clonal evolution in chronic lymphocytic leukemia. (cdc.gov)
  • Clonal evolution explains unpredictable leukemia disease course By Lynda Williams, Senior medwireNews Reporter Researchers have revealed the complicated clonal evolution of chronic lymphocytic leukemia , giving insight into the variation in disease training course and its own response to treatment. (parkerfirstbaptist.org)
  • By applying this analysis approach to 149 chronic lymphocytic leukemia (CLL) cases, we discovered earlier and later cancer drivers, uncovered patterns of clonal evolution in CLL and linked the presence of subclones harboring driver mutations with adverse clinical outcome. (grantome.com)
  • If common clones are selected against and rare clones gain a concomitant advantage, we expect that clonal turnover should be faster during parasite epidemics than between them. (deepdyve.com)
  • Darwinian evolution and tiding clones in multiple myeloma. (wikilite.com)
  • On the other hand, genetic diversity in specific clones of Ph + B-ALL that drive clonal evolution has recently come to light. (wiley.com)
  • Antimicrobial resistance, penicillin-binding protein sequences, and pilus islet carriage in relation to clonal evolution of Streptococcus pneumoniae serotype 19A in Russia, 2002-2013. (vanopijnenlab.com)
  • Clonal changes of serotype 19A pneumococci have been appreciated in conjunction with growing prevalence of this serotype after implementation of the seven-valent pneumococcal conjugate vaccine (PCV7). (vanopijnenlab.com)
  • In the present study, we characterized serotype 19A pneumococci collected in Russia within a decade preceding the implementation of PCV vaccination and described their clonal evolution. (vanopijnenlab.com)
  • Our findings demonstrate that the clonal structure of serotype 19A pneumococci may evolve without PCV pressure. (vanopijnenlab.com)
  • Influx and expansion in the Southern Chilean ocean of a highly clonal V. parahaemolyticus (serotype O3:K6) population from South East Asia caused one of the largest seafood-related diarrhea outbreaks in the world. (biomedcentral.com)
  • NEW YORK (GenomeWeb) - A public-private team from the US and UK has successfully used exome and targeted amplicon sequencing of tissue biopsies and circulating tumor DNA to characterize the genomic architecture of a breast cancer patient's tumor and track its clonal evolution over time in response to various therapies. (genomeweb.com)
  • Collectively, these results provide insights into clonal evolution underlying ibrutinib relapse and prompt further investigation on genomic abnormalities that have clinical application potential. (bloodadvances.org)
  • Clonal evolution and selection of tumor cells can be assessed by examining genomic and proteomic alterations of tumor samples obtained from multiple sites of primary and metastatic sites. (clinicaltrials.gov)
  • Population genetic and genomic studies have shed light on the evolutionary mechanisms underlying speciation processes, adaptive evolution and long-distance dispersal of highly damaging pathogens in agro-ecosystems. (royalsocietypublishing.org)
  • The phenotypic consequences of large genomic architecture modifications within a clonal bacterial population are rarely evaluated because of the difficulties associated with using molecular approaches in a mixed population. (biomedcentral.com)
  • This study provides insight into the field of bacterial genome architecture and further elucidates the role played by clonal genomic variation in bacterial genome evolution. (biomedcentral.com)
  • However, comparative genomic analyses of genomic variants within a clonal population are rarely undertaken because of the difficulties involved in using molecular approaches in a mixed population. (biomedcentral.com)
  • Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow. (asm.org)
  • The majority of isolates were distributed among clonal complex (CC) 663 (28%), CC230 (25%), CC156, and CC320 (14% each). (vanopijnenlab.com)
  • New isolates of V. parahaemolyticus that are able to cause diarrhea in humans by ingestion of seafood periodically emerge through their continuous evolution in the ocean. (biomedcentral.com)
  • This, together with their potentially large effective population sizes and the fact that their reproduction is not obligately sexual, suggests that clonal interference may play an important role in their adaptive evolution. (sciencemag.org)
  • When this distribution falls off slower than exponentially, clonal interference alone reasonably describes which mutations dominate the adaptation, although it gives a misleading picture of the evolutionary dynamics. (genetics.org)
  • Clonal hematopoiesis is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells. (wikipedia.org)
  • As clonal evolution could allow Bcr-Abl independent proliferation, we analyzed its impact on the outcome of 71 AP patients treated with 600 mg of imatinib mesylate. (bloodjournal.org)
  • While many of the genetic and epigenetic abnormalities in neoplasms are probably neutral evolution , many have been shown to increase the proliferation of the mutant cells, or decrease their rate of death ( apoptosis ). (wikipedia.org)
  • The integrin-binding domain of CD98 was necessary and sufficient for full clonal expansion, pointing to a role for adhesive signaling in T cell proliferation and autoimmune disease. (jimmunol.org)
  • Ex vivo experimental studies have suggested that the expression of AID in precursor B cells may promote clonal evolution towards leukemia. (cicancer.org)
  • Conversely, recent studies have revealed that clonal evolution of premalignant B-cell precursors toward leukemia as a result of in vivo infection exposure takes place through acquisition of secondary genetic events no related to mutated hotspots for AID activity in both patient-derived B-ALL and mouse models mimicking the human genetic predisposition to B-ALL. (cicancer.org)
  • In patients who had Richter transformation, we found that the transformed cells were clonal descendants of circulating leukemia cells but continued to undergo evolution and drifts. (bloodadvances.org)
  • Clonal evolution explains unpredictable leukemia disease course By Lynda Williams. (parkerfirstbaptist.org)
  • Examination of the pathophysiology of these diseases has provided interesting insights into not only the hierarchy of leukemia stem cells but also their clonal evolution. (wiley.com)
  • Our study indicates a high potential for further evolution of the clonal growth form in R. reptans, but not for its plasticity, and it demonstrates that the clonal growth form does not evolve independently of other clonal lifehistory characteristics. (uni-konstanz.de)
  • Finally, to define if subclonal mutations are predictive of clinical outcome, we will systematically identify clonal and subclonal mutations in serial samples prospectively collected from 300 subjects enrolled on a landmark phase III clinical trial of frontline fludarabine-based chemotherapy and characterize the dynamic changes in the clonal landscape within individual cases. (grantome.com)
  • The ability to predict hematologic response, relapse and clonal evolution could improve treatment allocation. (springer.com)
  • The important outcomes to be considered following IST are hematologic response, relapse and clonal evolution to MDS and survival. (springer.com)
  • For all these reasons it is worthy to explore the evolution over time of antibiotic nonsusceptibility and its relation to clonality, since it may have preventive and therapeutic consequences. (asm.org)
  • Elucidation of the molecular and genetic pathways driving clonal evolution may inform surveillance and risk stratification, and may lead to the development of novel therapeutic strategies. (cdc.gov)
  • Thus, the integrin-binding domain of CD98 is required for Ag-driven T cell clonal expansion in the pathogenesis of an autoimmune disease and may represent a useful therapeutic target. (jimmunol.org)
  • This can be exemplified by pioneering studies at The Genome Institute leveraging deep, targeted sequencing of single nucleotide variants (SNVs) discovered using whole genome sequencing (WGS) to calculate variant allele frequencies (VAFs) for studying clonal evolution over time. (grantome.com)
  • Modern descriptions of biological evolution will typically elaborate on major contributing factors to evolution such as the formation of local micro-environments, mutational robustness, molecular degeneracy , and cryptic genetic variation. (wikipedia.org)
  • The clonal make‐up and turnover of the Daphnia host population was tracked with high temporal resolution from 1998 until 2013, using first allozyme and later microsatellite markers. (deepdyve.com)
  • The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease. (evmedreview.com)
  • In this review, the implications of "trunk and branch" tumor evolution for drug discovery approaches and emerging evidence that low-frequency somatic events may drive tumor growth through paracrine signaling fostering a tumor ecologic niche are discussed. (aacrjournals.org)
  • Dykhuizen DE , Polin DS , Dunn JJ , Wilske B , Preac-Mursic V , Dattwyler RJ , Borrelia burgdorferi is clonal: implications for taxonomy and vaccine development. (cdc.gov)
  • Specifically, clinical presentation, risk of thrombosis, and clonal evolution are distinct in patients with myeloproliferative neoplasms who acquire JAK2V617F mutations prior to TET2 mutations compared to those that acquire TET2 mutations before JAK2V617F. (ncri.org.uk)
  • We can divide multicellularity into two distinct types, aggregative and clonal - which we will discuss in turn (1). (plos.org)
  • The evolution of sex contains two related, yet distinct, themes: its origin and its maintenance. (wikipedia.org)