keyword
MENU ▼
Read by QxMD icon Read
search

Phenotypic heterogeneity

keyword
https://www.readbyqxmd.com/read/29226804/systems-pharmacology-dissection-of-cholesterol-regulation-reveals-determinants-of-large-pharmacodynamic-variability-between-cell-lines
#1
Peter Blattmann, David Henriques, Michael Zimmermann, Fabian Frommelt, Uwe Sauer, Julio Saez-Rodriguez, Ruedi Aebersold
In individuals, heterogeneous drug-response phenotypes result from a complex interplay of dose, drug specificity, genetic background, and environmental factors, thus challenging our understanding of the underlying processes and optimal use of drugs in the clinical setting. Here, we use mass-spectrometry-based quantification of molecular response phenotypes and logic modeling to explain drug-response differences in a panel of cell lines. We apply this approach to cellular cholesterol regulation, a biological process with high clinical relevance...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29226381/a-robust-and-powerful-two-step-testing-procedure-for-local-ancestry-adjusted-allelic-association-analysis-in-admixed-populations
#2
Qing Duan, Zheng Xu, Laura M Raffield, Suhua Chang, Di Wu, Ethan M Lange, Alex P Reiner, Yun Li
Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping...
December 10, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29225571/heterogenic-distribution-of-aromatic-l-amino-acid-decarboxylase-neurons-in-the-rat-spinal-cord
#3
Li-Qun Ren, Meng Chen, Hans Hultborn, Sen Guo, Yifan Zhang, Mengliang Zhang
Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the synthesis of serotonin, dopamine, and certain trace amines and is present in a variety of organs including the brain and spinal cord. It is previously reported that in mammalian spinal cord AADC cells (called D-cells) were largely confined to a region around the central canal and that they do not produce monoamines. To date, there has not been a detailed description of their distribution and morphology in mammals. In the present study this issue is systematically investigated using immunohistochemistry...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29224756/novel-pax3-mutations-causing-waardenburg-syndrome-type-1-in-tunisian-patients
#4
Mediha Trabelsi, Malek Nouira, Faouzi Maazoul, Lilia Kraoua, Rim Meddeb, Ines Ouertani, Imen Chelly, Valérie Benoit, Ghazi Besbes, Ridha Mrad
Waardenburg syndrome (WS) is an auditory-pigmentary disease characterized by a clinical and genetic variability. WS is classified into four types depending on the presence or absence of additional symptoms: WS1, WS2, WS3 and WS4. Type 1 and 3 are mostly caused by PAX3 mutations, while type 2 and type 4 are genetically heterogeneous. The aims of this study are to confirm the diagnostic of WS1 by the sequencing of PAX3 gene and to evaluate the genotype phenotype correlation. A clinical classification was established for 14 patients WS, as proposed by the Waardenburg Consortium, and noted a predominance of type 1 and type 2 with 6 patients WS1, 7 patients WS2 and 1 patient WS3...
December 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/29224588/alteration-of-the-microrna-expression-profile-in-familial-mediterranean-fever-patients
#5
Yeliz Z Akkaya-Ulum, Banu Balci-Peynircioglu, Omer Karadag, Fehime K Eroglu, Umut Kalyoncu, Sedat Kiraz, Ali Ihsan Ertenli, Seza Özen, Engin Yilmaz
OBJECTIVES: Phenotypic heterogeneity in familial Mediterranean fever (FMF) disease indicated that FMF is not a simple monogenic disease. Therefore it has been suggested that epigenetic factors can be one of the reason for the variations. We undertook this study to test potential involvement of miRNAs in the pathogenesis of FMF. METHODS: miRNA array was performed on whole blood RNA samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-)...
November 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29223885/three-novel-slc2a1-mutations-in-bulgarian-patients-with-different-forms-of-genetic-generalized-epilepsy-reflecting-the-clinical-and-genetic-diversity-of-glut1-deficiency-sydnrome
#6
Nevyana Ivanova, Valentina Peycheva, Kunka Kamenarova, Dalia Kancheva, Irina Tsekova, Iliana Aleksandrova, Dimitrina Hristova, Ivan Litvinenko, Diana Todorova, Gergana Sarailieva, Petya Dimova, Veselin Tomov, Veneta Bozhinova, Vanio Mitev, Radka Kaneva, Albena Jordanova
PURPOSE: GLUT1-deficiency syndrome (GLUT1-DS) is a metabolic brain disorder with a great clinical heterogeneity underlined by various mutations in the SLC2A1 gene which make the clinical and genetic diagnosis complicated. The purpose of our study is to investigate the genetic defects affecting the SLC2A1 gene in a group of Bulgarian patients with genetic generalized epilepsy (GGE), and to bring new insights into the molecular pathology of GLUT1-DS that would strengthen the genotype-phenotype correlations and improve the diagnostic procedure...
November 28, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29222989/disrupted-circuits-in-mouse-models-of-autism-spectrum-disorder-and-intellectual-disability
#7
REVIEW
Carla Em Golden, Joseph D Buxbaum, Silvia De Rubeis
Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity...
December 5, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29222693/neuroblastoma-pathogenesis-deregulation-of-embryonic-neural-crest-development
#8
REVIEW
Julie A Tomolonis, Saurabh Agarwal, Jason M Shohet
Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development...
December 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29222311/role-of-the-microenvironment-across-histological-subtypes-of-nhl
#9
REVIEW
Karin Tarte
Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221729/high-dimensional-phenotypic-mapping-of-human-dendritic-cells-reveals-interindividual-variation-and-tissue-specialization
#10
Marcela Alcántara-Hernández, Rebecca Leylek, Lisa E Wagar, Edgar G Engleman, Tibor Keler, M Peter Marinkovich, Mark M Davis, Garry P Nolan, Juliana Idoyaga
Given the limited efficacy of clinical approaches that rely on ex vivo generated dendritic cells (DCs), it is imperative to design strategies that harness specialized DC subsets in situ. This requires delineating the expression of surface markers by DC subsets among individuals and tissues. Here, we performed a multiparametric phenotypic characterization and unbiased analysis of human DC subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a...
November 28, 2017: Immunity
https://www.readbyqxmd.com/read/29221262/differences-in-airway-remodeling-and-airway-inflammation-among-moderate-severe-asthma-clinical-phenotypes
#11
Wen-Jing Ye, Wei-Guo Xu, Xue-Jun Guo, Feng-Feng Han, Juan Peng, Xiao-Ming Li, Wen-Bin Guan, Li-Wei Yu, Jin-Yuan Sun, Zhi-Lei Cui, Lin Song, Yue Zhang, Yan-Min Wang, Tian-Yun Yang, Xia-Hui Ge, Di Yao, Song Liu
Background: To identify asthma clinical phenotypes using cluster analysis and improve our understanding of heterogeneity in asthma. Methods: Clustering approaches were applied to 203 patients who were diagnosed with asthma in XinHua Hospital (January 2012 to December 2015). One hundred and twenty patients underwent multi-slice spiral computed tomography (MSCT) examination and 30 underwent bronchial mucosal biopsy for evaluation of airway remodeling and airway inflammation among the phenotypes...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29220555/multiparameter-cytometric-analysis-of-complex-cellular-response
#12
Šárka Šimečková, Radek Fedr, Ján Remšík, Zuzana Kahounová, Eva Slabáková, Karel Souček
Complex analysis of cellular responses after experimental treatment is important for screening, mechanistic understanding of treatment effects, and the identification of sensitive and resistant cell phenotypes. Modern multicolor flow cytometry has demonstrated its power for such analyses. Here, we introduce a multiparametric protocol for complex analysis of cytokinetics by the simultaneous detection of seven fluorescence parameters. This analysis includes the detection of two surface markers for immunophenotyping, analysis of proliferation based on the cell cycle and the measurement of incorporated nucleoside analogue 5-ethynyl-2'-deoxyuridine (EdU) in newly synthesized DNA, analysis of DNA damage using an anti-phospho-histone H2A...
December 8, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#13
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29219656/modulating-secreted-components-of-tumor-microenvironment-a-masterstroke-in-tumor-therapeutics
#14
Himadri Patel, Pritish Nilendu, Devashree Jahagirdar, Jayanta K Pal, Nilesh Kumar Sharma
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29218873/session-introduction-challenges-of-pattern-recognition-in-biomedical-data
#15
Shefali Setia Verma, Anurag Verma, Anna Okula Basile, Marta-Byrska Bishop, Christian Darabos
The analysis of large biomedical data often presents with various challenges related to not just the size of the data, but also to data quality issues such as heterogeneity, multidimensionality, noisiness, and incompleteness of the data. The data-intensive nature of computational genomics problems in biomedical informatics warrants the development and use of massive computer infrastructure and advanced software tools and platforms, including but not limited to the use of cloud computing. Our session aims to address these challenges in handling big data for designing a study, performing analysis, and interpreting outcomes of these analyses...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29217145/neurodevelopmental-synaptopathies-insights-from-behaviour-in-rodent-models-of-synapse-gene-mutations
#16
REVIEW
J Luo, R H Norris, S L Gordon, J Nithianantharajah
The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated...
December 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29216908/clinical-and-neuropathological-features-of-als-ftd-with-tia1-mutations
#17
Veronica Hirsch-Reinshagen, Cyril Pottier, Alexandra M Nicholson, Matt Baker, Ging-Yuek R Hsiung, Charles Krieger, Pheth Sengdy, Kevin B Boylan, Dennis W Dickson, Marsel Mesulam, Sandra Weintraub, Eileen Bigio, Lorne Zinman, Julia Keith, Ekaterina Rogaeva, Sasha A Zivkovic, David Lacomis, J Paul Taylor, Rosa Rademakers, Ian R A Mackenzie
Mutations in the stress granule protein T-cell restricted intracellular antigen 1 (TIA1) were recently shown to cause amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). Here, we provide detailed clinical and neuropathological descriptions of nine cases with TIA1 mutations, together with comparisons to sporadic ALS (sALS) and ALS due to repeat expansions in C9orf72 (C9orf72+). All nine patients with confirmed mutations in TIA1 were female. The clinical phenotype was heterogeneous with a range in the age at onset from late twenties to the eighth decade (mean = 60 years) and disease duration from one to 6 years (mean = 3 years)...
December 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29216878/adaptive-phenotype-drives-resistance-to-androgen-deprivation-therapy-in-prostate-cancer
#18
Nicoletta Ferrari, Ilaria Granata, Matteo Capaia, Marina Piccirillo, Mario Rosario Guarracino, Roberta Venè, Antonella Brizzolara, Andrea Petretto, Elvira Inglese, Martina Morini, Simonetta Astigiano, Adriana Agnese Amaro, Francesco Boccardo, Cecilia Balbi, Paola Barboro
BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS: Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP...
December 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29216508/quantitative-biomarkers-for-prediction-of-epidermal-growth-factor-receptor-mutation-in-non-small-cell-lung-cancer
#19
Liwen Zhang, Bojiang Chen, Xia Liu, Jiangdian Song, Mengjie Fang, Chaoen Hu, Di Dong, Weimin Li, Jie Tian
OBJECTIVES: To predict epidermal growth factor receptor (EGFR) mutation status using quantitative radiomic biomarkers and representative clinical variables. METHODS: The study included 180 patients diagnosed as of non-small cell lung cancer (NSCLC) with their pre-therapy computed tomography (CT) scans. Using a radiomic method, 485 features that reflect the heterogeneity and phenotype of tumors were extracted. Afterwards, these radiomic features were used for predicting epidermal growth factor receptor (EGFR) mutation status by a least absolute shrinkage and selection operator (LASSO) based on multivariable logistic regression...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29214518/outcome-of-older-persons-admitted-to-intensive-care-unit-mortality-prognosis-factors-dependency-scores-and-ability-trajectory-within-1%C3%A2-year-a-prospective-cohort-study
#20
Claude Level, Eric Tellier, Patrick Dezou, Karim Chaoui, Aissa Kherchache, Philippe Sejourné, Anne Marie Rullion-Pac Soo
BACKGROUND: The outcome and functional trajectory of older persons admitted to intensive care (ICU) unit remain a true question for critical care physicians and geriatricians, due to the heterogeneity of geriatric population, heterogeneity of practices and absence of guidelines. AIM: To describe the 1-year outcome, prognosis factors and functional trajectory for older people admitted to ICU. METHODS: In a prospective 1-year cohort study, all patients aged 75 years and over admitted to our ICU were included according to a global comprehensive geriatric assessment...
December 6, 2017: Aging Clinical and Experimental Research
keyword
keyword
42256
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"