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Phenotypic heterogeneity

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https://www.readbyqxmd.com/read/28646471/decoding-early-myelopoiesis-from-dynamics-of-core-endogenous-network
#1
Hang Su, Gaowei Wang, Ruoshi Yuan, Junqiang Wang, Ying Tang, Ping Ao, Xiaomei Zhu
A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, seven years ago a group of Chinese scientists started a program aiming to obtain quantitative connections between tumors and network dynamics. Many interesting results have been obtained...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28646407/associations-of-red-and-processed-meat-intake-with-major-molecular-pathological-features-of-colorectal-cancer
#2
Prudence R Carr, Lina Jansen, Stefanie Bienert, Wilfried Roth, Esther Herpel, Matthias Kloor, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
Red and processed meat is an established risk factor for colorectal cancer (CRC). However, exact mechanisms to explain the associations remain unclear. Few studies have investigated the association with CRC by molecular tumor features, which could provide relevant information on associated molecular pathways. In this population-based case-control study from Germany (DACHS), 2449 cases and 2479 controls provided information on risk factors of CRC and completed a food frequency questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between meat intake and risk of CRC by molecular pathologic features and specific subtypes...
June 23, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28645745/dna-methylation-of-dlg4-and-gja-1-of-human-hippocampus-and-prefrontal-cortex-in-major-depression-is-unchanged-in-comparison-to-healthy-individuals
#3
Oliver Kaut, Amit Sharma, Ina Schmitt, René Hurlemann, Ullrich Wüllner
Epigenetic alterations provide a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. In context to major depression disorder (MDD), where postmortem and neuroimaging studies provide insights into dysfunctional brain regions, involvement of genetic heterogeneity also revealed the complexity of this disorder. Despite intensive research during the past several decades and information from genome wide studies, pathophysiology of depressive disorders remained elusive...
June 20, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28645641/homogenizing-bacterial-cell-factories-analysis-and-engineering-of-phenotypic-heterogeneity
#4
REVIEW
Dennis Binder, Thomas Drepper, Karl-Erich Jaeger, Frank Delvigne, Wolfgang Wiechert, Dietrich Kohlheyer, Alexander Grünberger
In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization...
June 20, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28645163/variations-in-chloroplast-movement-and-chlorophyll-fluorescence-among-chloroplast-division-mutants-under-light-stress
#5
Siddhartha Dutta, Jeffrey A Cruz, Saif M Imran, Jin Chen, David M Kramer, Katherine W Osteryoung
Chloroplasts divide to maintain consistent size, shape, and number in leaf mesophyll cells. Altered expression of chloroplast division proteins in Arabidopsis results in abnormal chloroplast morphology. To better understand the influence of chloroplast morphology on chloroplast movement and photosynthesis, we compared the chloroplast photorelocation and photosynthetic responses of a series of Arabidopsis chloroplast division mutants with a wide variety of chloroplast phenotypes. Chloroplast movement was monitored by red light reflectance imaging of whole plants under increasing intensities of white light...
June 22, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28644708/the-arabidopsis-mind-mutation-causes-aberrant-ftsz1-ring-placement-and-moderate-heterogeneity-of-chloroplasts-in-the-leaf-epidermis
#6
Makoto T Fujiwara, Mana Yasuzawa, Shun Sasaki, Takeshi Nakano, Yasuo Niwa, Shigeo Yoshida, Tomoko Abe, Ryuuichi D Itoh
Symmetric division of leaf mesophyll chloroplasts requires MinD and MinE, which work together to suppress division other than at the mid-chloroplast. arc11 is a MinD loss-of-function mutant of Arabidopsis thaliana. In arc11 plants, asymmetric chloroplast division, as well as its delay or arrest, results in extreme size polymorphism of chloroplasts in mature mesophyll cells. The current study examined chloroplast phenotypes in the epidermis of arc11 leaves. Fluorescence microscopy analysis revealed that epidermal chloroplasts in mature leaves exhibited moderate heterogeneity in size...
June 23, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28644558/current-understanding-of-cancer-stem-cells-review-of-their-radiobiology-and-role-in-head-and-neck-cancers
#7
REVIEW
Paul Ambrose Reid, Puthenparampil Wilson, Yanrui Li, Loredana Gabriela Marcu, Eva Bezak
Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose...
June 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28643964/-diagnosis-and-prognosis-of-low-back-pain-contribution-and-limitations-of-the-clinical-approach
#8
Stéphane Genevay, Federico Balagué
The label « non-specific » that applies to 85% of patients complaining of low back pain is an heterogeneous group including different phenotypes. The identification of the anatomic origin of pain is often impossible in a primary care encounter. However, the physician can identify several elements that are useful to establish some diagnosis, foresee the evolution and tailor therapeutic decisions.
June 21, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28643126/cancer-stem-cells-in-hepatocellular-carcinoma
#9
REVIEW
Tamer Yagci, Metin Cetin, Pelin Balcik Ercin
BACKGROUND: Hepatocellular carcinoma is one of the most common cancers and the second leading cause of cancer-related deaths worldwide. Only a small proportion of patients benefit from curative treatment and the prognosis is very poor for the majority of cases due to late presentation, resistance to chemotherapy and high recurrence rate. In recent years, progress in stem cell biology allowed us to explain that hierarchically organized cancer stem cells (CSCs) drive histological and functional heterogeneity of hematological malignancies and solid tumors...
June 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#10
REVIEW
Shinsuke Hirabayashi, Marcin W Wlodarski, Emilia Kozyra, Charlotte M Niemeyer
The GATA2 gene codes for a master hematopoietic transcription factor that is essential for the proliferation and maintenance of hematopoietic stem and progenitor cells. Heterozygous germline mutations in GATA2 have been initially associated with several clinical entities that are now collectively defined as GATA2 deficiency. Despite pleiotropic clinical manifestations, the high propensity for the development of myelodysplastic syndromes (MDS) constitutes the most common clinical denominator of this major MDS predisposition syndrome...
June 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28642794/adipose-tissue-derived-mesenchymal-stem-cells-have-a-heterogenic-cytokine-secretion-profile
#11
Yongkang Wu, Martin J Hoogduijn, Carla C Baan, Sander S Korevaar, Ronella de Kuiper, Lin Yan, Lanlan Wang, Nicole M van Besouw
Mesenchymal stem cells derived from adipose tissue (ASC) have immune regulatory function, which makes them interesting candidates for cellular therapy. ASC cultures are however heterogeneous in phenotype. It is unclear whether all ASC contribute equally to immunomodulatory processes. ASC are also responsive to cytokine stimulation, which may affect the ratio between more and less potent ASC populations. In the present study, we determined IL-6 receptor (CD126 and CD130 subunits) and IFN-γ receptor (CD119) expression on ASC by flow cytometry...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28642365/phenotypic-diagnosis-of-lineage-and-differentiation-during-sake-yeast-breeding
#12
Shinsuke Ohnuki, Hiroki Okada, Anne Friedrich, Yoichiro Kanno, Tetsuya Goshima, Hirokazu Hasuda, Masaaki Inahashi, Naoto Okazaki, Hiroyasu Tamura, Ryo Nakamura, Dai Hirata, Hisashi Fukuda, Hitoshi Shimoi, Katsuhiko Kitamoto, Daisuke Watanabe, Joseph Schacherer, Takeshi Akao, Yoshikazu Ohya
Sake yeast was developed exclusively in Japan. Its diversification during breeding remains largely uncharacterized. To evaluate the breeding processes of the sake lineage, we thoroughly investigated the phenotypes and differentiation of 27 sake yeast strains using high-dimensional, single-cell morphological phenotyping. Although the genetic diversity of the sake yeast lineage is relatively low, its morphological diversity has expanded substantially compared to that of the Saccharomyces cerevisiae species as a whole...
June 22, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28641778/clinical-presentations-metabolic-abnormalities-and-end-organ-complications-in-patients-with-familial-partial-lipodystrophy
#13
Baris Akinci, Huseyin Onay, Tevfik Demir, Şenay Savas-Erdeve, Ramazan Gen, Ilgin Yildirim Simsir, Fatma Ela Keskin, Mehmet Sercan Erturk, Ayse Kubat Uzum, Guzin Fidan Yaylali, Nilufer Kutbay Ozdemir, Tahir Atik, Samim Ozen, Banu Sarer Yurekli, Tugce Apaydin, Canan Altay, Gulcin Akinci, Leyla Demir, Abdurrahman Comlekci, Mustafa Secil, Elif Arioglu Oral
OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641519/neural-stem-cells-and-human-induced-pluripotent-stem-cells-to-model-rare-cns-diseases
#14
Lidia De Filippis, Cristina Zalfa, Daniela Ferrari
Despite the great effort spent over the last decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them remain still unclear. In particular, the study of rare brain diseases is hurdled by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue has efficiently allowed to model several neurological diseases "in a dish" and has also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting...
June 15, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28641508/is-longevity-a-heritable-trait-evidence-for-non-genomic-influence-from-an-extended-longevity-phenotype-of-drosophila-melanogaster
#15
S Deepashree, Thimmappa Shivanandappa, Saraf R Ramesh
BACKGROUND: Although genetic variations are heritable, some quantitative traits like longevity may have non-genomic influence in heritability. Laboratory-selected inbred strains of extended longevity phenotype of Drosophila offer an opportunity to study the inheritance of longevity. OBJECTIVE: To examine the heritability of longevity in an extended longevity phenotype of Drosophila melanogaster using reciprocal cross effects in F1 and F2 generations. METHODS: Lifespan variations of virgin and mated flies in parent, F1 and F2 generations were investigated using reciprocal crosses between normal and long lifespan lines of inbred population of D...
June 15, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28640903/type-2b-von-willebrand-disease-with-or-without-large-multimers-a-distinction-of-the-two-sides-of-the-disorder-is-long-overdue
#16
Alessandra Casonato, Viviana Daidone, Eva Galletta, Antonella Bertomoro
Most, but not all patients with type 2B von Willebrand disease (VWD)-which features gain-of-function mutations in the A1 domain of von Willebrand factor (VWF)-have no circulating large VWF multimers. Similarities and differences were analysed in 33 type 2B patients, 12 with a normal and 21 with an abnormal multimer pattern, to see whether they should be considered separately. The minimum aggregating dose of ristocetin was similarly reduced in both patient groups, and modulated by their underlying VWF mutations...
2017: PloS One
https://www.readbyqxmd.com/read/28638591/replicable-in-vivo-physiological-and-behavioral-phenotypes-of-the-shank3b-null-mutant-mouse-model-of-autism
#17
Sameer C Dhamne, Jill L Silverman, Chloe E Super, Stephen H T Lammers, Mustafa Q Hameed, Meera E Modi, Nycole A Copping, Michael C Pride, Daniel G Smith, Alexander Rotenberg, Jacqueline N Crawley, Mustafa Sahin
BACKGROUND: Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28637664/expanded-repertoire-of-rasgrp2-variants-responsible-for-platelet-dysfunction-and-severe-bleeding
#18
Sarah K Westbury, Matthias Canault, Daniel Greene, Emilse Bermejo, Katharine Hanlon, Michele P Lambert, Carolyn M Millar, Paquita Nurden, Samya G Obaji, Shoshana Revel-Vilk, Chris Van Geet, Kate Downes, Sofia Papadia, Salih Tuna, Christopher Watt, Nihr BioResource-Rare Diseases Consortium, Kathleen Freson, Michael A Laffan, Willem H Ouwehand, Marie-Christine Alessi, Ernest Turro, Andrew D Mumford
Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterised. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in three pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2 variants, we compared high-throughput sequencing and phenotype data from 2,042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5,422 controls...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28637600/distinguishing-between-nociceptive-and-neuropathic-components-in-chronic-low-back-pain-using-behavioural-evaluation-and-sensory-examination
#19
N Spahr, D Hodkinson, K Jolly, S Williams, M Howard, M Thacker
BACKGROUND: Diagnosis of chronic low back pain (CLBP) is traditionally predicated on identifying underlying pathological or anatomical causes, with treatment outcomes modest at best. Alternately, it is suggested that identification of underlying pain mechanisms with treatments targeted towards specific pain phenotypes may yield more success. Differentiation between nociceptive and neuropathic components of CLBP is problematic; evidence suggests that clinicians fail to identify a significant neuropathic component in many CLBP patients...
February 2017: Musculoskeletal Science & Practice
https://www.readbyqxmd.com/read/28637421/a-novel-pathway-based-distance-score-enhances-assessment-of-disease-heterogeneity-in-gene-expression
#20
Xiting Yan, Anqi Liang, Jose Gomez, Lauren Cohn, Hongyu Zhao, Geoffrey L Chupp
BACKGROUND: Distance based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. An alternative method to examine disease phenotypes is to use pre-defined biological pathways. These pathways have been shown to be perturbed in different ways in different subjects who have similar clinical features...
June 20, 2017: BMC Bioinformatics
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