Read by QxMD icon Read

Forced gene mutation

Maria Siemionow, Joanna Cwykiel, Ahlke Heydemann, Jesus Garcia, Enza Marchese, Krzysztof Siemionow, Erzsebet Szilagyi
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD...
March 15, 2018: Stem Cell Reviews
Libing Shen, Qili Shi, Wenyuan Wang
The role of genetic components in cancer development is an area of interest for cancer biologists in general. Intriguingly, some genes have both oncogenic and tumor-suppressor functions. In this study, we systematically identified these genes through database search and text mining. We find that most of them are transcription factors or kinases and exhibit dual biological functions, e.g., that they both positively and negatively regulate transcription in cells. Some cancer types such as leukemia are over-represented by them, whereas some common cancer types such as lung cancer are under-represented by them...
March 13, 2018: Oncogenesis
Li Zheng, Gui-Min Zhang, Yan-Peng Dong, Yi-Fan Wen, Dong Dong, Chu-Zhao Lei, Xing-Lei Qi, Hong Chen, Li-Jun Huo, Yong-Zhen Huang
As a member of MYLK family, MYLK4 gene may play a vital role in muscle development. In this study, one novel single-nucleotide polymorphism (SNP) was identified the bovine MYLK4 by sequencing pooled DNA samples (pool-Seq) and forced polymerase chain reaction-restriction fragment length polymorphism (forced PCR-RFLP) methods. Overall, we reported one mutation (SNP1) in the intron 10 region within the bovine MYLK4 gene in 559 individuals representing five main cattle breeds from China (Nanyang, NY; Qinchuan; Jiaxian, JX; Pinan cattle; and Caidamu cattle, CDM)...
March 14, 2018: Animal Biotechnology
Carolyn J Baglole, Feng Liang, Hussein Traboulsi, Angela Rico de Souza, Christian Giordano, Josephine T Tauer, Frank Rauch, Basil J Petrof
BACKGROUND: Osteogenesis imperfecta (OI) is most often caused by mutations in type I collagen genes. Respiratory complications have been largely attributed to spine and ribcage deformities. We hypothesized that direct involvement of the pulmonary parenchyma and/or diaphragm by the disease may occur. METHODS: In Col1a1Jrt/+ mice, a model of severe dominant OI, mean linear intercept length (Lm) was used to assess distal airspace size. Cross-sectional area (CSA) and myosin heavy chain (MyHC) phenotype of diaphragm muscle fibers, as well as contractile properties, were determined...
March 14, 2018: Pediatric Research
Abdul Q Khan, Shilpa Kuttikrishnan, Kodappully S Siveen, Kirti S Prabhu, Muralitharan Shanmugakonar, Hamda Al Naemi, Mohammad Haris, Said Dermime, Shahab Uddin
Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and associated pathological conditions including cancer. In general, RAS is the main upstream regulator of the highly conserved signaling mechanisms associated with a plethora of important cellular activities vital for normal homeostasis...
March 7, 2018: Seminars in Cancer Biology
Debi Prasad Mohapatra, Santosh Kumar Singh, Minu Sahoo, Shashank Patole, Mitali Mishra, Nagen Kumar Debata, Harapriya Mohapatra
PURPOSE: Antibiotic resistance patterns often exhibit geographical variations. Periodic analyses of resistance spectra and phylogenetic trends are important guides for facilitating judicious use of therapeutic interventions. The present study retrospectively analysed the infection trends, resistance patterns, and clonal relationships between isolates of Klebsiella spp. from a tertiary care hospital. METHODOLOGY: Bacterial isolates were collected from January 2013 to June 2014 and their resistance profiles were identified using an automated bacterial identification system...
March 9, 2018: Journal of Medical Microbiology
Li-Av Segev-Zarko, Gal Kapach, Michaele Josten, Yoel Alexander Klug, Hans-Georg Sahl, Yechiel Shai
Multidrug resistant bacteria possess various mechanisms that can sense environmental stresses such as antibiotics and antimicrobial peptides, and rapidly respond to defend themselves. Two known defense strategies are biofilm formation and lipopolysaccharide (LPS) modification. Though LPS modifications are observed in biofilm embedded bacteria, their effect on biofilm formation is unknown. Using biochemical and biophysical methods coupled with confocal, atomic force microscopy and transmission electron microscopy, we show that biofilm formation is promoted in a Pseudomonas aeruginosa PAO1 strain with a loss of function mutation in the arnB gene...
March 8, 2018: Biochemistry
S Mu, Y Cui, W Wang, L Wang, H Xu, O Zhu, D Zhu
OBJECTIVES: The aim of this study was to characterise a novel mutation in the gene encoding RhAG in order to elucidate a molecular mechanism for Rh antigen expression and spherocytosis. BACKGROUND: Rhesus-associated glycoprotein (RhAG) is critical for maintaining the structure and stability of erythrocytes. Single missense mutations in the gene encoding RhAG are sufficient to induce spherocytosis and deficiencies in Rh complex formation. We report a novel missense mutation that incompletely disrupts Rh antigen expression and selectively knocks out RhD antigen expression...
March 6, 2018: Transfusion Medicine
Hichem Tasfaout, Valentina M Lionello, Christine Kretz, Pascale Koebel, Nadia Messaddeq, Deborah Bitz, Jocelyn Laporte, Belinda S Cowling
Myotubular myopathy, or X-linked centronuclear myopathy, is a severe muscle disorder representing a significant burden for patients and their families. It is clinically characterized by neonatal and severe muscle weakness and atrophy. Mutations in the myotubularin (MTM1) gene cause myotubular myopathy, and no specific curative treatment is available. We previously found that dynamin 2 (DNM2) is upregulated in both Mtm1 knockout and patient muscle samples, whereas its reduction through antisense oligonucleotides rescues the clinical and histopathological features of this myopathy in mice...
February 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Esther Frohnmeyer, Paulina Deptula, Tuula A Nyman, Pia K S Laine, Helena Vihinen, Lars Paulin, Petri Auvinen, Eija Jokitalo, Vieno Piironen, Pekka Varmanen, Kirsi Savijoki
This study compared the secretomes (proteins exported out of the cell) of Propionibacterium freudenreichii of different origin to identify plausible adaptation factors. Phylosecretomics indicated strain-specific variation in secretion of adhesins/invasins (SlpA, InlA), cell-wall hydrolysing (NlpC60 peptidase, transglycosylase), protective (RpfB) and moonlighting (DnaK, GroEL, GaPDH, IDH, ENO, ClpB) enzymes and/or proteins. Detailed secretome comparison suggested that one of the cereal strains (JS14) released a tip fimbrillin (FimB) in to the extracellular milieu, which was in line with the electron microscopy and genomic analyses, indicating the lack of surface-associated fimbrial-like structures, predicting a mutated type-2 fimbrial gene cluster (fimB-fimA-srtC2) and production of anchorless FimB...
February 28, 2018: Microbial Biotechnology
Binghui Liu, Chong Wu, Xiaotong Shen, Wei Pan
Next-generation sequencing studies on cancer somatic mutations have discovered that driver mutations tend to appear in most tumor samples, but they barely overlap in any single tumor sample, presumably because a single driver mutation can perturb the whole pathway. Based on the corresponding new concepts of coverage and mutual exclusivity, new methods can be designed for de novo discovery of mutated driver pathways in cancer. Since the computational problem is a combinatorial optimization with an objective function involving a discontinuous indicator function in high dimension, many existing optimization algorithms, such as a brute force enumeration, gradient descent and Newton's methods, are practically infeasible or directly inapplicable...
September 2017: Annals of Applied Statistics
Gaia Giovannelli, Giorgia Giacomazzi, Hanne Grosemans, Maurilio Sampaolesi
Introduction - Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the β-sarcoglycan gene, which is expressed in skeletal, cardiac and smooth muscle. β-sarcoglycan deficient (Sgcb-null) mice develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. Methods - We performed morphological (histological and cellular characterization) and functional (isometric tetanic force and fatigue) analyses in dystrophic mice. Comparisons studies were carried out in 1-month-old (clinical onset of the disease) and 7-month-old mice among controls (C57/BL6, Rag2/γc-null), immunocompetent and immunodeficient dystrophic mice (Sgcb-null, Sgcb/Rag2/γc-null mice respectively)...
February 24, 2018: Muscle & Nerve
Irene Franco, Anna Johansson, Karl Olsson, Peter Vrtačnik, Pär Lundin, Hafdis T Helgadottir, Malin Larsson, Gwladys Revêchon, Carla Bosia, Andrea Pagnani, Paolo Provero, Thomas Gustafsson, Helene Fischer, Maria Eriksson
Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle...
February 23, 2018: Nature Communications
Guo-Wei Jheng, Sung Sik Hur, Chia-Ming Chang, Chun-Chieh Wu, Jia-Shing Cheng, Hsiao-Hui Lee, Bon-Chu Chung, Yang-Kao Wang, Keng-Hui Lin, Juan C Del Álamo, Shu Chien, Jin-Wu Tsai
Cell migration is a critical process during development, tissue repair, and cancer metastasis. It requires complex processes of cell adhesion, cytoskeletal dynamics, and force generation. Lis1 plays an important role in the migration of neurons, fibroblasts and other cell types, and is essential for normal development of the cerebral cortex. Mutations in human LIS1 gene cause classical lissencephaly (smooth brain), resulting from defects in neuronal migration. However, how Lis1 may affect force generation in migrating cells is still not fully understood...
February 19, 2018: Biochemical and Biophysical Research Communications
Chen-Ching Yuan, Katarzyna Kazmierczak, Jingsheng Liang, Zhiqun Zhou, Sunil Yadav, Aldrin V Gomes, Thomas C Irving, Danuta Szczesna-Cordary
Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1 million people in the United States, but the underlying mechanisms remain poorly understood. In this study, we aimed to determine the biomechanical and structural causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain. Transgenic D94A (aspartic acid-to-alanine) mice were created and investigated by echocardiography and invasive hemodynamic and molecular structural and functional assessments...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jie Li, Hiroki Shima, Hironari Nishizawa, Masatoshi Ikeda, Andrey Brydun, Mitsuyo Matsumoto, Hiroki Kato, Yuriko Saiki, Liang Liu, Miki Watanabe-Matsui, Kenji Iemura, Kozo Tanaka, Takuma Shiraki, Kazuhiko Igarashi
The transcription repressor BACH1 performs mutually independent dual roles in transcription regulation as well as chromosome alignment during mitosis by supporting polar ejection force of mitotic spindle. We now found that the mitotic spindles became oblique relative to the adhesion surface following endogenous BACH1 depletion in HeLa cells. This spindle orientation rearrangement was rescued by re-expression of BACH1 depending on its interactions with HMMR and CRM1, both of which are required for the positioning of mitotic spindle, but independently of its DNA binding activity...
February 19, 2018: Biochemical Journal
Mickaël Poidevin, Mari Sato, Ipek Altinoglu, Manon Delaplace, Chikara Sato, Yoshiharu Yamaichi
Conjugative plasmids are one of the main driving force of wide-spreading of multidrug resistance (MDR) bacteria. They are self-transmittable via conjugation as carrying the required set of genes and cis -acting DNA locus for direct cell-to-cell transfer. IncI incompatibility plasmids are nowadays often associated with extended-spectrum beta-lactamases producing Enterobacteria in clinic and environment. pESBL-EA11 was isolated from Escherichia coli O104:H4 outbreak strain in Germany in 2011. During the previous study identifying transfer genes of pESBL-EA11, it was shown that transposon insertion at certain DNA region of the plasmid, referred to as Hft, resulted in great enhancement of transfer ability...
2018: Frontiers in Microbiology
David S Hersh, Sen Peng, Jimena G Dancy, Rebeca Galisteo, Jennifer M Eschbacher, Rudy J Castellani, Jonathan E Heath, Teklu Legesse, Anthony J Kim, Graeme F Woodworth, Nhan L Tran, Jeffrey A Winkles
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme...
February 16, 2018: Journal of Neuro-oncology
Naoki Yamamoto, Rino Isshiki, Yuto Kawai, Daiki Tanaka, Tetsushi Sekiguchi, Shinya Matsumoto, Satoshi Tsuneda
Bacterial persisters are phenotypic variants that survive the treatment of lethal doses of growth-targeting antibiotics without mutations. Although the mechanism underlying persister formation has been studied for decades, how the persister phenotype is switched on and protects itself from antibiotics has been elusive. In this study, we focused on the lactate dehydrogenase gene (ldhA) that was upregulated in an Escherichia coli persister-enriched population. A survival rate assay using an ldhA-overexpressing strain showed that ldhA expression induced persister formation...
February 12, 2018: Journal of Bioscience and Bioengineering
Noreen von Cramon-Taubadel, Stephen J Lycett
In the study of cultural evolution, observed among-group affinity patterns reflect the effects of processes such as mutation (e.g. innovation and copying error), between-group interaction (culture flow), drift and selection. As in biology, cultural affinity patterns are often spatially correlated, making it difficult to distinguish between the opposing geographically mediated forces of divergence and interaction, which cause groups to become more distinct or similar over time, respectively. Analogous difficulties are faced by evolutionary biologists examining the relationship between biological affinity and geography, particularly at lower taxonomic levels where the potential for gene flow between lineages is greatest...
April 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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"