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Phenotypic heterogeneity

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https://www.readbyqxmd.com/read/28823022/long-term-bisphosphonate-therapy-in-osteogenesis-imperfecta
#1
REVIEW
A Biggin, C F Munns
PURPOSE OF REVIEW: Osteogenesis imperfecta (OI) is a genetic bone disorder resulting in bone fragility. It has a heterogeneous phenotype which typically includes reduced bone mass, multiple fractures, deformity, and chronic disability. Bisphosphonate treatment remains the first-line medical management, but there is still debate on aspects of its effectiveness. This review summarizes current knowledge about long-term bisphosphonate use in OI with recommendations on clinical application...
August 19, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28822693/whisker-dependent-responsiveness-of-c57bl-6j-to-different-behavioral-test-paradigms
#2
Seenu Haridas, Ramya Ganapathi, Mayank Kumar, Kailash Manda
Whisker trimming is very common in C57BL/6J mice. Dewhiskering may lead to an alteration in the thalamocortical connectivity and relevant behavioral functions. Since C57BL/6J is a commonly used strain for neurobehavioral studies, it is important to examine how whisker dependent heterogeneity affects the internal validity of behavioral phenotypes. The present study aimed to investigate the responsiveness of mice to different behavioral test paradigms in the presence or absence of whiskers. We employed two models of whisker deprivation: Acute Whisker Desensitization (AWD) and Chronic Habitual Dewhiskering (CHD)...
August 16, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28821810/extracting-intercellular-signaling-network-of-cancer-tissues-using-ligand-receptor-expression-patterns-from-whole-tumor-and-single-cell-transcriptomes
#3
Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821788/bioenergetic-adaptations-in-chemoresistant-ovarian-cancer-cells
#4
Sajad Dar, Jasdeep Chhina, Ismail Mert, Dhananjay Chitale, Thomas Buekers, Hareena Kaur, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan
Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies have shown that certain cancer cells display increased oxidative phosphorylation or high metabolically active phenotype. Cellular bioenergetic profiling of 13 established and 12 patient derived ovarian cancer cell lines revealed significant bioenergetics diversity. The bioenergetics phenotype of ovarian cancer cell lines correlated with functional phenotypes of doubling time and oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820904/parametric-studies-of-metabolic-cooperativity-in-escherichia-coli-colonies-strain-and-geometric-confinement-effects
#5
Joseph R Peterson, John A Cole, Zaida Luthey-Schulten
Characterizing the complex spatial and temporal interactions among cells in a biological system (i.e. bacterial colony, microbiome, tissue, etc.) remains a challenge. Metabolic cooperativity in these systems can arise due to the subtle interplay between microenvironmental conditions and the cells' regulatory machinery, often involving cascades of intra- and extracellular signalling molecules. In the simplest of cases, as demonstrated in a recent study of the model organism Escherichia coli, metabolic cross-feeding can arise in monoclonal colonies of bacteria driven merely by spatial heterogeneity in the availability of growth substrates; namely, acetate, glucose and oxygen...
2017: PloS One
https://www.readbyqxmd.com/read/28819450/circulating-tumor-cells-moving-biological-insights-into-detection
#6
REVIEW
Lichan Chen, Ann M Bode, Zigang Dong
Circulating tumor cells (CTCs) have shown promising potential as liquid biopsies that facilitate early detection, prognosis, therapeutic target selection and monitoring treatment response. CTCs in most cancer patients are low in abundance and heterogeneous in morphological and phenotypic profiles, which complicate their enrichment and subsequent characterization. Several methodologies for CTC enrichment and characterization have been developed over the past few years. However, integrating recent advances in CTC biology into these methodologies and the selection of appropriate enrichment and characterization methods for specific applications are needed to improve the reliability of CTC biopsies...
2017: Theranostics
https://www.readbyqxmd.com/read/28819021/phenotypic-heterogeneity-of-circulating-tumor-cells-informs-clinical-decisions-between-ar-signaling-inhibitors-and-taxanes-in-metastatic-prostate-cancer
#7
Howard I Scher, Ryon P Graf, Nicole Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica Louw, Lyndsey Dugan, Hebert Alberto Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan V Dittamore
The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28817917/re-phosphorylation-induced-conformational-dynamics-in-an-intrinsically-disordered-protein-and-potential-role-in-phenotypic-heterogeneity
#8
Anthony Atala
No abstract text is available yet for this article.
September 2017: Journal of Urology
https://www.readbyqxmd.com/read/28817687/morphologic-phenotypic-and-transcriptomic-characterization-of-classically-and-alternatively-activated-canine-blood-derived-macrophages-in-vitro
#9
Franziska Heinrich, Annika Lehmbecker, Barbara B Raddatz, Kristel Kegler, Andrea Tipold, Veronika M Stein, Arno Kalkuhl, Ulrich Deschl, Wolfgang Baumgärtner, Reiner Ulrich, Ingo Spitzbarth
Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28817611/the-directed-migration-of-gonadal-distal-tip-cells-in-caenorhabditis-elegans-requires-ngat-1-a-%C3%A3-1-4-n-acetylgalactosaminyltransferase-enzyme
#10
Joseph Veyhl, Robert J Dunn, Wendy L Johnston, Alexa Bennett, Lijia W Zhang, James W Dennis, Harry Schachter, Joseph G Culotti
Glycoproteins such as growth factor receptors and extracellular matrix have well-known functions in development and cancer progression, however, the glycans at sites of modification are often heterogeneous molecular populations which makes their functional characterization challenging. Here we provide evidence for a specific, discrete, well-defined glycan modification and regulation of a stage-specific cell migration in Caenorhabditis elegans. We show that a chain-terminating, putative null mutation in the gene encoding a predicted β1,4-N-acetylgalactosaminyltransferase, named ngat-1, causes a maternally rescued temperature sensitive (ts) defect in the second phase of the three phase migration pattern of the posterior, but not the anterior, hermaphrodite Distal Tip Cell (DTC)...
2017: PloS One
https://www.readbyqxmd.com/read/28816949/whole-exome-sequencing-identifies-a-kcnj12-mutation-as-a-cause-of-familial-dilated-cardiomyopathy
#11
Hai-Xin Yuan, Kai Yan, Dong-Yan Hou, Zhi-Yong Zhang, Hua Wang, Xin Wang, Juan Zhang, Xiao-Rong Xu, Yan-Hong Liang, Wen-Shu Zhao, Lin Xu, Lin Zhang
Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases.A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#12
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28815944/neonatal-fractures-as-a-presenting-feature-of-lmod3-associated-congenital-myopathy
#13
Megan Abbott, Mahim Jain, Rachel Pferdehirt, Yuqing Chen, Alyssa Tran, Mehmet B Duz, Mehmet Seven, Richard A Gibbs, Donna Muzny, Brendan Lee, Ronit Marom, Lindsay C Burrage
Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family...
August 16, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28815891/cystic-kidneys-in-fetal-walker-warburg-syndrome-with-pomt2-mutation-intrafamilial-phenotypic-variability-in-four-siblings-and-review-of-literature
#14
Marwa M Nabhan, Nour ElKhateeb, Daniela A Braun, Sungho Eun, Sahar N Saleem, Heon YungGee, Friedhelm Hildebrandt, Neveen A Soliman
Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes...
August 17, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28815647/wildlife-disease-ecology-from-the-individual-to-the-population-insights-from-a-long-term-study-of-a-naturally-infected-european-badger-population
#15
Jenni L McDonald, Andrew Robertson, Matthew J Silk
1. Long-term individual-based datasets on host-pathogen systems are a rare and valuable resource for understanding the infectious disease dynamics in wildlife. A study of European badgers (Meles meles) naturally infected with bovine tuberculosis (bTB) at Woodchester Park in Gloucestershire (UK) has produced a unique dataset, facilitating investigation of a diverse range of epidemiological and ecological questions with implications for disease management. 2. Since the 1970s this badger population has been monitored with a systematic mark-recapture regime yielding a dataset of >15,000 captures of >3000 individuals, providing detailed individual life-history, morphometric, genetic, reproductive and disease data...
August 16, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28815638/new-insights-into-the-origin-and-the-genetic-status-of-the-balkan-donkey-from-serbia
#16
L J Stanisic, J M Aleksic, V Dimitrijevic, P Simeunovic, U Glavinic, J Stevanovic, Z Stanimirovic
The Balkan donkey (Equus asinus L.) is commonly regarded as a large-sized, unselected, unstructured and traditionally managed donkey breed. We assessed the current genetic status of the three largest E. asinus populations in the central Balkans (Serbia) by analysing the variability of nuclear microsatellites and the mitochondrial (mtDNA) control region of 77 and 49 individuals respectively. We further analysed our mtDNA dataset along with 209 published mtDNA sequences of ancient and modern individuals from 19 European and African populations to provide new insights into the origin and the history of the Balkan donkey...
August 16, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28814851/effect-of-allergic-phenotype-on-treatment-response-to-inhaled-bronchodilators-with-or-without-inhaled-corticosteroids-in-patients-with-copd
#17
Shih-Lung Cheng, Hsu Hui Wang, Ching-Hsiung Lin
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder encompassing different phenotypes with different responses to treatment. The present 1-year, two-center hospital-based study investigated whether the plasma immunoglobulin E (IgE) level and/or eosinophil cell count could be used as biomarkers to stratify patients with COPD according to predicted responses to inhaled corticosteroids (ICS)-based therapy. METHODS: A hospital-data based cohort study of COPD patients treated at two territory hospital centers was conducted for 1 year...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28814770/rapid-phenotypic-individualization-of-bacterial-sister-cells
#18
Sander K Govers, Antoine Adam, Hendrik Blockeel, Abram Aertsen
A growing bacterium typically divides into two genetically identical and morphologically similar sister cells and eventually gives rise to a clonal population. Nevertheless, significant phenotypic differentiation among isogenic cells frequently occurs, with the resulting heterogeneity in cellular behavior often ensuring population level growth and survival in complex and unpredictable environments. Although several mechanisms underlying the generation of phenotypic heterogeneity have been elucidated, the speed with which identical sister cells tend to phenotypically diverge from each other has so far remained unaddressed...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814615/single-cell-gene-expression-of-the-bovine-blastocyst
#19
Veronica M Negrón-Pérez, Yanping Zhang, Peter J Hansen
The first two differentiation events in the blastocyst result in three cell types - epiblast, trophectoderm (TE), and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells from dissociated blastocysts was used to determine transcript abundance for 96 genes implicated as cell lineage markers in other species or potentially involved in developmental processes...
August 16, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28812906/recent-advances-in-ct-imaging-in-chronic-obstructive-pulmonary-disease
#20
Sandeep Bodduluri, Joseph M Reinhardt, Eric A Hoffman, John D Newell, Surya P Bhatt
Lung imaging is increasingly being used to diagnose, quantify and phenotype chronic obstructive pulmonary disease (COPD). Although spirometry is the gold standard for the diagnosis of COPD and for severity staging, the role of computed tomography (CT) imaging has expanded in both clinical practice and research. COPD is a heterogeneous disease with considerable variability in clinical features, radiographic disease, progression and outcomes. Recent studies have examined the utility of CT imaging in enhancing diagnostic certainty, improving phenotyping, predicting disease progression and prognostication, patient selection for intervention, and also in furthering our understanding of the complex pathophysiology of this disease...
August 16, 2017: Annals of the American Thoracic Society
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