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https://www.readbyqxmd.com/read/28732234/computational-modelling-of-genome-scale-metabolic-networks-and-its-application-to-cho-cell-cultures
#1
REVIEW
Živa Rejc, Lidija Magdevska, Tilen Tršelič, Timotej Osolin, Rok Vodopivec, Jakob Mraz, Eva Pavliha, Nikolaj Zimic, Tanja Cvitanović, Damjana Rozman, Miha Moškon, Miha Mraz
Genome-scale metabolic models (GEMs) have become increasingly important in recent years. Currently, GEMs are the most accurate in silico representation of the genotype-phenotype link. They allow us to study complex networks from the systems perspective. Their application may drastically reduce the amount of experimental and clinical work, improve diagnostic tools and increase our understanding of complex biological phenomena. GEMs have also demonstrated high potential for the optimisation of bio-based production of recombinant proteins...
July 8, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28729848/the-functional-genetics-of-handedness-and-language-lateralization-insights-from-gene-ontology-pathway-and-disease-association-analyses
#2
Judith Schmitz, Stephanie Lor, Rena Klose, Onur Güntürkün, Sebastian Ocklenburg
Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28727318/appropriate-cyclic-tensile-strain-promotes-biological-changes-of-cranial-base-synchondrosis-chondrocytes
#3
F Chu, Q Feng, Z Hu, G Shen
OBJECTIVES: This study was designed to clarify biological changes of cranial base synchondrosis chondrocytes (CBSCs) upon cyclic tensile strain (CTS) loading which simulated orthopaedic mechanical protraction on cranial base synchondroses (CBS). MATERIAL AND METHODS: A two-step digestion method was used to isolate CBSCs obtained from 1-week-old Sprague Dawley rats. Immunohistochemical staining of type II collagen and Sox9 was conducted to identify chondrocytes. A CTS of 1 Hz and 10% elongation was applied to the second passage of CBSCs by FX-5000™ Tension System for 24 hours...
August 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#4
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#5
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28720727/impact-of-paracoccin-gene-silencing-on-paracoccidioides-brasiliensis-virulence
#6
Fabrício F Fernandes, Aline F Oliveira, Taise N Landgraf, Cristina Cunha, Agostinho Carvalho, Patrícia E Vendruscolo, Relber A Gonçales, Fausto Almeida, Thiago A da Silva, Fernando Rodrigues, Maria Cristina Roque-Barreira
Among the endemic deep mycoses in Latin America, paracoccidioidomycosis (PCM), caused by thermodimorphic fungi of the Paracoccidioides genus, is a major cause of morbidity. Disease development and its manifestations are associated with both host and fungal factors. Concerning the latter, several recent studies have employed the methodology of gene modulation in P. brasiliensis using antisense RNA (AsRNA) and Agrobacterium tumefaciens-mediated transformation (ATMT) to identify proteins that influence fungus virulence...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28717716/breast-cancer-and-african-ancestry-lessons-learned-at-the-10-year-anniversary-of-the-ghana-michigan-research-partnership-and-international-breast-registry
#7
Evelyn Jiagge, Joseph Kwaku Oppong, Jessica Bensenhaver, Francis Aitpillah, Kofi Gyan, Ishmael Kyei, Ernest Osei-Bonsu, Ernest Adjei, Michael Ohene-Yeboah, Kathy Toy, Karen Eubanks Jackson, Marian Akpaloo, Dorcas Acheampong, Beatrice Antwi, Faustina Obeng Agyeman, Zainab Alhassan, Linda Ahenkorah Fondjo, Osei Owusu-Afriyie, Robert Newman Brewer, Amma Gyamfuah, Barbara Salem, Timothy Johnson, Max Wicha, Sofia Merajver, Celina Kleer, Judy Pang, Emmanuel Amankwaa-Frempong, Azadeh Stark, Francis Abantanga, Lisa Newman, Baffour Awuah
Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan...
October 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28716860/novel-mechanisms-of-piezo1-dysfunction-in-hereditary-xerocytosis
#8
Edyta Glogowska, Eve R Schneider, Yelena Maksimova, Vincent P Schulz, Kimberly Lezon-Geyda, John Wu, Kottayam Radhakrishnan, Siobán B Keel, Donald Mahoney, Alison M Freidmann, Rachel A Altura, Elena O Gracheva, Sviatoslav N Bagriantsev, Theodosia A Kalfa, Patrick G Gallagher
Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We utilized next generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected HX and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore region domain. Several mutations were novel and demonstrated ethnic specificity. We characterized these mutations using genomic, bioinformatic, cell biology, and physiology-based functional assays...
July 17, 2017: Blood
https://www.readbyqxmd.com/read/28716510/evaluation-of-in-vivo-and-in-vitro-models-of-toxicity-by-comparison-of-toxicogenomics-data-with-the-literature
#9
Katerina Taškova, Jean-Fred Fontaine, Ralf Mrowka, Miguel A Andrade-Navarro
Toxicity affecting humans is studied by observing the effects of chemical substances in animal organisms (in vivo) or in animal and human cultivated cell lines (in vitro). Toxicogenomics studies collect gene expression profiles and histopathology assessment data for hundreds of drugs and pollutants in standardized experimental designs using different model systems. These data are an invaluable source for analyzing genome-wide drug response in biological systems. However, a problem remains that is how to evaluate the suitability of heterogeneous in vitro and in vivo systems to model the many different aspects of human toxicity...
July 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28716439/renal-cell-carcinoma-unclassified-with-medullary-phenotype-poorly-differentiated-adenocarcinomas-overlapping-with-renal-medullary-carcinoma
#10
Deepika Sirohi, Steven C Smith, Chisato Ohe, Piergiuseppe Colombo, Mukul Divatia, Ema Dragoescu, Priya Rao, Michelle S Hirsch, Ying-Bei Chen, Rohit Mehra, Mahul B Amin
Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma, arising in the collecting system, and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype (RCCU-MP), based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of five such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy...
July 14, 2017: Human Pathology
https://www.readbyqxmd.com/read/28716410/review-nectar-biology-from-molecules-to-ecosystems
#11
REVIEW
Rahul Roy, Anthony J Schmitt, Jason B Thomas, Clay J Carter
Plants attract mutualistic animals by offering a reward of nectar. Specifically, floral nectar (FN) is produced to attract pollinators, whereas extrafloral nectar (EFN) mediates indirect defenses through the attraction of mutualist predatory insects to limit herbivory. Nearly 90% of all plant species, including 75% of domesticated crops, benefit from animal-mediated pollination, which is largely facilitated by FN. Moreover, EFN represents one of the few defense mechanisms for which stable effects on plant health and fitness have been demonstrated in multiple systems, and thus plays a crucial role in the resistance phenotype of plants producing it...
September 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28715970/scaffold-in-scaffold-potential-to-induce-growth-and-differentiation-of-cardiac-progenitor-cells
#12
Matteo Ciocci, Federico Mochi, Felicia Carotenuto, Emilia Di Giovanni, Paolo Prosposito, Roberto Francini, Fabio De Matteis, Igor Reshetov, Mauro Casalboni, Sonia Melino, Paolo Di Nardo
The design of reliable biocompatible and biodegradable scaffolds remains one of the most important challenges for tissue engineering. In fact, properly designed scaffolds must display an adequate and interconnected porosity to facilitate cell spreading and colonization of the inner layers, and must release physical signals concurring to modulate cell function to ultimately drive cell fate. In the present study, a combination of optimal mechanical and biochemical properties has been considered to design a one-component 3D multitextured hydrogel scaffold in order to favor cell-scaffold interactions...
July 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28715713/metastasis-systems-biology-how-are-macro-environmental-signals-transmitted-into-microenvironmental-cues-for-disseminated-tumor-cells
#13
REVIEW
Candice Alexandra Grzelak, Cyrus Michael Ghajar
Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one...
July 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28715416/signatures-of-inflammation-and-impending-multiple-organ-dysfunction-in-the-hyperacute-phase-of-trauma-a-prospective-cohort-study
#14
Claudia P Cabrera, Joanna Manson, Joanna M Shepherd, Hew D Torrance, David Watson, M Paula Longhi, Mimoza Hoti, Minal B Patel, Michael O'Dwyer, Sussan Nourshargh, Daniel J Pennington, Michael R Barnes, Karim Brohi
BACKGROUND: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28715383/discrimination-and-characterization-of-heterocellular-populations-using-quantitative-imaging-techniques
#15
Colleen M Garvey, Torin A Gerhart, Shannon M Mumenthaler
Cellular processes are complex and result from the interplay between multiple cell types and their environment. Existing cell biology techniques often do not allow for accurate interpretation of this interplay. Using a quantitative imaging-based approach, we present a high-content protocol for characterizing the dynamic phenotypic responses (i.e. morphology changes, proliferation, apoptosis) of heterogeneous cell populations to changes in environmental stimuli. We highlight our ability to distinguish between cell types based upon either fluorescence intensity or inherent morphology features depending on the application...
June 30, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28713938/effects-of-age-on-biological-and-functional-characterization-of-adipose%C3%A2-derived-stem-cells-from-patients-with-end%C3%A2-stage-liver-disease
#16
Yanyu Jin, Lei Yang, Yanyan Zhang, Wei Gao, Zhi Yao, Yang Song, Yuliang Wang
Adipose‑derived mesenchymal stromal cells (ADSCs) possess a multilineage potential and immunoregulatory properties, and may have great potential in autologous cell‑based technologies. The aim of the present study was to investigate how the age of patients with benign end‑stage liver disease affected the biological and functional characteristics of ADSCs, which is important for increasing the potential effectiveness of autologous cell therapy. ADSCs were obtained and cultured from three distinct age groups: Infant, adult and elderly...
July 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28708248/oral-and-upper-gastrointestinal-crohn-s-disease
#17
REVIEW
Robyn Laube, Ken Liu, Mark Schifter, Jessica L Yang, Michael K Suen, Rupert W Leong
Crohn's disease is a heterogeneous, inflammatory condition that can affect any location of the gastrointestinal tract. Proximal gastrointestinal involvement occurs in 0.5-16% of patients, and it is usually diagnosed after recognition of intestinal disease. Symptoms are often mild and non-specific, however upper gastrointestinal disease predicts a more severe Crohn's phenotype with a greater frequency of complications such as obstruction and perforation. Gastroscopy and biopsy is the most sensitive diagnostic investigation...
July 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28707483/investigational-drugs-in-development-for-focal-segmental-glomerulosclerosis
#18
Howard Trachtman
Focal segmental glomerulosclerosis is an important cause of end stage kidney disease and is a paradigm for the study of glomerular scarring. There are no FDA approved treatments for this condition. Current therapies, assessed based on reduction in proteinuria, are generally effective in a subset of patients which suggests that FSGS is a heterogeneous group of glomerular disorders or podocytopathies that converge on a common histopathological phenotype. Areas covered: We searched for investigational drugs agents that target different pathophysiological pathways using the key words 'FSGS' and 'podocyte' in American and European clinical trial registers (clinicaltrials...
July 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28707108/clinical-and-biological-insights-from-the-university-of-california-san-francisco-prospective-and-longitudinal-cohort
#19
Bryan S Benn, Zoe Lehman, Sharon A Kidd, Melissa Ho, Sara Sun, Joris Ramstein, Nicholas K Arger, Christine P Nguyen, Robert Su, Antonio Gomez, Jeffrey M Gelfand, Laura L Koth
INTRODUCTION: Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. METHODS: We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics...
July 13, 2017: Lung
https://www.readbyqxmd.com/read/28704566/development-and-characterization-of-a-human-three-dimensional-chondrosarcoma-culture-for-in-vitro-drug-testing
#20
Aurélien Voissiere, Elodie Jouberton, Elise Maubert, Françoise Degoul, Caroline Peyrode, Jean-Michel Chezal, Élisabeth Miot-Noirault
It has been suggested that chemoresistance of chondrosarcoma (CHS), the cartilage tumor, is caused by the phenotypic microenvironmental features of the tumor tissue, mainly the chondrogenic extracellular matrix (ECM), and hypoxia. We developed and characterized a multicellular tumor spheroid (MCTS) of human chondrosarcoma HEMC-SS cells to gain insight into tumor cell biology and drug response. At Day 7, HEMC-SS spheroids exhibited a homogeneous distribution of proliferative Ki-67 positive cells, whereas in larger spheroids (Day 14 and Day 20), proliferation was mainly localized in the periphery...
2017: PloS One
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