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Phenotypic heterogeneity

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https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-non-malignant-plasmablast-and-germinal-center-b-cell-populations
#1
Cara Ellen Wogsland, Allison Rae Greenplate, Arne Kolstad, June Helen Myklebust, Jonathan Michael Irish, Kanutte Huse
BACKGROUND: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the non-malignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. METHODS: Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, non-malignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933557/atypical-presentation-and-treatment-response-in-a-child-with-familial-hypercholesterolemia-having-a-novel-ldlr-mutation
#2
S Varma, A D McIntyre, R A Hegele
Familial hypercholesterolemia (FH) is an autosomal codominantly inherited disease. The severity of clinical presentation depends on the zygosity of the mutations in the LDLR, APOB, or PCSK9 genes. The homozygous form (HoFH) is associated with high mortality rate by third decade of life, while individuals with HeFH begin to suffer from premature cardiovascular disease in fourth or fifth decade of life. Statin drugs have helped to improve the biochemical profile and life expectancy in HeFH, while they are only minimally effective in HoFH...
December 9, 2016: JIMD Reports
https://www.readbyqxmd.com/read/27933532/precise-network-modeling-of-systems-genetics-data-using-the-bayesian-network-webserver
#3
Jesse D Ziebarth, Yan Cui
The Bayesian Network Webserver (BNW, http://compbio.uthsc.edu/BNW ) is an integrated platform for Bayesian network modeling of biological datasets. It provides a web-based network modeling environment that seamlessly integrates advanced algorithms for probabilistic causal modeling and reasoning with Bayesian networks. BNW is designed for precise modeling of relatively small networks that contain less than 20 nodes. The structure learning algorithms used by BNW guarantee the discovery of the best (most probable) network structure given the data...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933066/functionally-diverse-nk-like-t-cells-are-effectors-and-predictors-of-successful-aging
#4
REVIEW
Joshua J Michel, Patricia Griffin, Abbe N Vallejo
The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933061/ncr1-expression-identifies-canine-natural-killer-cell-subsets-with-phenotypic-similarity-to-human-natural-killer-cells
#5
Jennifer A Foltz, Srinivas S Somanchi, Yanwen Yang, Arianexys Aquino-Lopez, Erin E Bishop, Dean A Lee
Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46), the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932592/the-role-of-adipose-tissue-in-cancer-associated-cachexia
#6
Janina A Vaitkus, Francesco S Celi
Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning...
December 8, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27932480/magi2-mutations-cause-congenital-nephrotic-syndrome
#7
Agnieszka Bierzynska, Katrina Soderquest, Philip Dean, Elizabeth Colby, Ruth Rollason, Caroline Jones, Carol D Inward, Hugh J McCarthy, Michael A Simpson, Graham M Lord, Maggie Williams, Gavin I Welsh, Ania B Koziell, Moin A Saleem
Steroid-resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932399/novel-hybrid-phenotype-revealed-in-small-cell-lung-cancer-by-a-transcription-factor-network-model-that-can-explain-tumor-heterogeneity
#8
Akshata R Udyavar, David J Wooten, Megan D Hoeksema, Mukesh Bansal, Andrea Califano, Lourdes Estrada, Santiago Schnell, Jonathan M Irish, Pierre P Massion, Vito Quaranta
Small cell lung cancer (SCLC) is a devastating disease due to its propensity for early invasion and refractory relapse after initial treatment response. Although these aggressive traits have been associated with phenotypic heterogeneity, our understanding of this association remains incomplete. To fill this knowledge gap, we inferred a set of 33 transcription factors (TF) associated with gene signatures of the known neuroendocrine/epithelial (NE) and non-neuroendocrine/mesenchymal-like (ML) SCLC phenotypes...
December 8, 2016: Cancer Research
https://www.readbyqxmd.com/read/27931687/l-form-transformation-phenomenon-in-mycobacterium-tuberculosis-associated-with-drug-tolerance-to-ethambutol
#9
Georgi Slavchev, Lilia Michailova, Nadya Markova
OBJECTIVE/BACKGROUND: Cell wall-deficient bacterial forms (L-forms) may occur along with resistance to factors that trigger their appearance. It is of interest to study the relationship between the L-form transformation of Mycobacterium tuberculosis and the exhibition of drug tolerance to ethambutol (EMB), an inhibitor of cell wall synthesis. METHODS: L-form variant was produced from a sensitive EMB strain of M. tuberculosis through a cryogenic stress treatment protocol and was subsequently cultivated in Middlebrook 7H9 semisolid medium, containing EMB in a minimal inhibitory concentration of 2mg/L...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27931297/chronic-obstructive-pulmonary-disease-phenotypes-biomarkers-and-prognostic-indicators
#10
Christopher E Brightling
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria are based on lung function impairment, symptoms, and exacerbation frequency but do not capture the heterogeneity of the disease in terms of the complex pathologic changes that occur within lung, the different airway inflammatory patterns, or the airway microbial ecology. Recognition of the importance of defining the heterogeneity of COPD has led to the identification of important phenotypes with specific biomarkers, treatment responses, and underlying pathophysiologic mechanisms...
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27930405/the-cost-of-crohn-s-disease-varied-health-care-expenditure-patterns-across-distinct-disease-trajectories
#11
Bhavana B Rao, Benjamin H Click, Ioannis E Koutroubakis, Claudia Ramos Rivers, Miguel Regueiro, Jason Swoger, Marc Schwartz, Jana Hashash, Arthur Barrie, Michael A Dunn, David G Binion
BACKGROUND: Patients with Crohn's disease (CD) encompass a heterogeneous disease spectrum, with variable health care utilization and expenditure patterns. Lémann Index (LI) is a metric that quantifies cumulative bowel damage and has shown utility in delineating distinct disease phenotypes. We aimed to characterize the financial burden from all medical care in CD cohort in relation to the variations in LI-based disease phenotypes. METHODS: CD patients with 5-year (y) follow-up from a prospective registry were included...
December 7, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27930094/cancer-stem-cell-hypothesis-for-therapeutic-innovation-in-clinical-oncology-taking-the-root-out-not-chopping-the-leaf
#12
Kevin Dzobo, Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Lamech M Mwapagha, Nasir Al-Awwad, Collet Dandara, M Iqbal Parker
Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27928030/emerging-therapies-for-inherited-retinal-degeneration
#13
REVIEW
Hendrik P N Scholl, Rupert W Strauss, Mandeep S Singh, Deniz Dalkara, Botond Roska, Serge Picaud, José-Alain Sahel
Inherited retinal degenerative diseases, a genetically and phenotypically heterogeneous group of disorders, affect the function of photoreceptor cells and are among the leading causes of blindness. Recent advances in molecular genetics and cell biology are elucidating the pathophysiological mechanisms underlying these disorders and are helping to identify new therapeutic approaches, such as gene therapy, stem cell therapy, and optogenetics. Several of these approaches have entered the clinical phase of development...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927758/mitochondrial-aging-is-there-a-mitochondrial-clock
#14
Dmitry B Zorov, Vasily A Popkov, Ljubava D Zorova, Ivan A Vorobjev, Irina B Pevzner, Denis N Silachev, Savva D Zorov, Stanislovas S Jankauskas, Valentina A Babenko, Egor Y Plotnikov
Fragmentation (fission) of mitochondria, occurring in response to oxidative challenge, leads to heterogeneity in the mitochondrial population. It is assumed that fission provides a way to segregate mitochondrial content between the "young" and "old" phenotype, with the formation of mitochondrial "garbage," which later will be disposed. Fidelity of this process is the basis of mitochondrial homeostasis, which is disrupted in pathological conditions and aging. The asymmetry of the mitochondrial fission is similar to that of their evolutionary ancestors, bacteria, which also undergo an aging process...
December 7, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27925477/relevance-of-meniscal-cell-regional-phenotype-to-tissue-engineering
#15
Shawn P Grogan, Chantal Pauli, Martin K Lotz, Darryl D D'Lima
PURPOSE: Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation. MATERIALS AND METHODS: Expression of 16 different surface molecules were examined by flow cytometry after monolayer culture for 24 h, 1 week, and 2 weeks...
December 7, 2016: Connective Tissue Research
https://www.readbyqxmd.com/read/27925178/adaptive-patterns-of-phenotypic-plasticity-in-laboratory-and-field-environments-in-drosophila-melanogaster
#16
Vinayak Mathur, Paul S Schmidt
Identifying mechanisms of adaptation to variable environments is essential in developing a comprehensive understanding of evolutionary dynamics in natural populations. Phenotypic plasticity allows for phenotypic change in response to changes in the environment, and as such may play a major role in adaptation to environmental heterogeneity. Here, the plasticity of stress response in D. melanogaster originating from two distinct geographic regions and ecological habitats was examined. Adults were given a short-term, 5-day exposure to combinations of temperature and photoperiod to elicit a plastic response for three fundamental aspects of stress tolerance that vary adaptively with geography...
December 7, 2016: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/27925158/mutations-in-dync2h1-the-cytoplasmic-dynein-2-heavy-chain-1-motor-protein-gene-cause-short-rib-polydactyly-type-i-saldino-noonan-type
#17
Nora Badiner, Stephanie Paige Taylor, Kimberly Forlenza, Ralph S Lachman, Michael Bamshad, Deborah Nickerson, Daniel H Cohn, Deborah Krakow
The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I-IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies...
December 7, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27924912/next-generation-systematics-an-innovative-approach-to-resolve-the-structure-of-complex-prokaryotic-taxa
#18
Vartul Sangal, Michael Goodfellow, Amanda L Jones, Edward C Schwalbe, Jochen Blom, Paul A Hoskisson, Iain C Sutcliffe
Prokaryotic systematics provides the fundamental framework for microbiological research but remains a discipline that relies on a labour- and time-intensive polyphasic taxonomic approach, including DNA-DNA hybridization, variation in 16S rRNA gene sequence and phenotypic characteristics. These techniques suffer from poor resolution in distinguishing between closely related species and often result in misclassification and misidentification of strains. Moreover, guidelines are unclear for the delineation of bacterial genera...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924065/the-more-the-messier-centrosome-amplification-as-a-novel-biomarker-for-personalized-treatment-of-colorectal-cancers
#19
REVIEW
Monica M Mahathre, Padmashree Cg Rida, Ritu Aneja
Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27924018/disgenet-a-comprehensive-platform-integrating-information-on-human-disease-associated-genes-and-variants
#20
Janet Piñero, Àlex Bravo, Núria Queralt-Rosinach, Alba Gutiérrez-Sacristán, Jordi Deu-Pons, Emilio Centeno, Javier García-García, Ferran Sanz, Laura I Furlong
The information about the genetic basis of human diseases lies at the heart of precision medicine and drug discovery. However, to realize its full potential to support these goals, several problems, such as fragmentation, heterogeneity, availability and different conceptualization of the data must be overcome. To provide the community with a resource free of these hurdles, we have developed DisGeNET (http://www.disgenet.org), one of the largest available collections of genes and variants involved in human diseases...
October 19, 2016: Nucleic Acids Research
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