keyword
MENU ▼
Read by QxMD icon Read
search

Mutational robustness

keyword
https://www.readbyqxmd.com/read/29239114/engineering-thermal-stability-and-solvent-tolerance-of-the-soluble-quinoprotein-pede-from-pseudomonas-putida-kt2440-with-a-heterologous-whole-cell-screening-approach
#1
Matthias Wehrmann, Janosch Klebensberger
Due to their ability for direct electron transfer to electrodes, the utilization of rare earth metals as cofactor, and their periplasmic localization, pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) represent an interesting class of biocatalysts for various biotechnological applications. For most biocatalysts protein stability is crucial, either to increase the performance of the protein under a given process condition or to maximize robustness of the protein towards mutational manipulations, which are often needed to enhance or introduce a functionality of interest...
December 14, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/29229990/tumor-suppressor-p53-links-ceramide-metabolism-to-dna-damage-response-through-alkaline-ceramidase-2
#2
Ruijuan Xu, Monica Garcia-Barros, Sally Wen, Fang Li, Chih-Li Lin, Yusuf A Hannun, Lina M Obeid, Cungui Mao
p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229913/a-metagenome-derived-thermostable-%C3%AE-glucanase-with-an-unusual-module-architecture-which-defines-the-new-glycoside-hydrolase-family-gh148
#3
Angel Angelov, Vu Thuy Trang Pham, Maria Übelacker, Silja Brady, Benedikt Leis, Nicole Pill, Judith Brolle, Matthias Mechelke, Matthias Moerch, Bernard Henrissat, Wolfgang Liebl
The discovery of novel and robust enzymes for the breakdown of plant biomass bears tremendous potential for the development of sustainable production processes in the rapidly evolving new bioeconomy. By functional screening of a metagenomic library from a volcano soil sample a novel thermostable endo-β-glucanase (EngU) which is unusual with regard to its module architecture and cleavage specificity was identified. Various recombinant EngU variants were characterized. Assignment of EngU to an existing glycoside hydrolase (GH) family was not possible...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229705/proteolytic-processing-of-neurexins-by-presenilins-sustains-synaptic-vesicle-release
#4
Emilia Servián-Morilla, Estefanía Robles-Lanuza, Ana C Sánchez-Hidalgo, Rafael J Camacho-Garcia, Juan A Paez-Gomez, Fabiola Mavillard, Carlos A Saura, Amalia Martinez-Mir, Francisco G Scholl
Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by Neurexins (Nrxns) and Neuroligins (Nlgns) bi-directionally orchestrate the function of pre- and postsynaptic terminals. Previous studies have shown that Presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Neurexin C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding...
December 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29229549/what-do-primary-immunodeficiencies-tell-us-about-the-essentiality-redundancy-of-immune-responses
#5
REVIEW
Alain Fischer, Antonio Rausell
Advances in genomics and medicine have enabled the identification of (currently) 346 primary immunodeficiencies (PIDs) caused by mutations in 336 different genes. Most of these PIDs are monogenic conditions with Mendelian inheritance. Given this large number, it is possible to analyze the distribution of PIDs associated with infections and/or immunopathology according to the nature of the defect - even though this exercise can be challenging and arguable because of the pleiotropic nature of some gene products...
December 8, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/29228836/complete-mtdna-sequencing-reveals-mutations-m-9185t-c-and-m-13513g-a-in-three-patients-with-leigh-syndrome
#6
Dita Pelnena, Birute Burnyte, Eriks Jankevics, Baiba Lace, Evelina Dagyte, Kristina Grigalioniene, Algirdas Utkus, Zita Krumina, Jolanta Rozentale, Irina Adomaitiene, Janis Stavusis, Liana Pliss, Inna Inashkina
The most common mitochondrial disorder in children is Leigh syndrome, which is a progressive and genetically heterogeneous neurodegenerative disorder caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the present study, a novel and robust method of complete mtDNA sequencing, which allows amplification of the whole mitochondrial genome, was tested. Complete mtDNA sequencing was performed in a cohort of patients with suspected mitochondrial mutations. Patients from Latvia and Lithuania (n = 92 and n = 57, respectively) referred by clinical geneticists were included...
December 12, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/29228193/deepsf-deep-convolutional-neural-network-for-mapping-protein-sequences-to-folds
#7
Jie Hou, Badri Adhikari, Jianlin Cheng
Motivation: Protein fold recognition is an important problem in structural bioinformatics. Almost all traditional fold recognition methods use sequence (homology) comparison to indirectly predict the fold of a target protein based on the fold of a template protein with known structure, which cannot explain the relationship between sequence and fold. Only a few methods had been developed to classify protein sequences into a small number of folds due to methodological limitations, which are not generally useful in practice...
December 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29228183/plasma-oxysterols-biomarkers-for-diagnosis-and-treatment-in-spastic-paraplegia-type-5
#8
Cecilia Marelli, Foudil Lamari, Dominique Rainteau, Alexandre Lafourcade, Guillaume Banneau, Lydie Humbert, Marie-Lorraine Monin, Elodie Petit, Rabab Debs, Giovanni Castelnovo, Elisabeth Ollagnon, Julie Lavie, Julie Pilliod, Isabelle Coupry, Patrick J Babin, Claire Guissart, Imen Benyounes, Urielle Ullmann, Gaetan Lesca, Christel Thauvin-Robinet, Pierre Labauge, Sylvie Odent, Claire Ewenczyk, Claude Wolf, Giovanni Stevanin, David Hajage, Alexandra Durr, Cyril Goizet, Fanny Mochel
The hereditary spastic paraplegias are an expanding and heterogeneous group of disorders characterized by spasticity in the lower limbs. Plasma biomarkers are needed to guide the genetic testing of spastic paraplegia. Spastic paraplegia type 5 (SPG5) is an autosomal recessive spastic paraplegia due to mutations in CYP7B1, which encodes a cytochrome P450 7α-hydroxylase implicated in cholesterol and bile acids metabolism. We developed a method based on ultra-performance liquid chromatography electrospray tandem mass spectrometry to validate two plasma 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) as diagnostic biomarkers in a cohort of 21 patients with SPG5...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29226533/the-anthelmintic-drug-niclosamide-and-its-analogues-activate-the-parkinson-s-disease-associated-protein-kinase-pink1
#9
Erica Barini, Ageo Miccoli, Federico Tinarelli, Katie Mulholand, Hachemi Kadri, Farhat Khanim, Laste Stojanovski, Kevin D Read, Kerry Burness, Julian J Blow, Youcef Mehellou, Miratul Muqit
Mutations in PINK1, which impair its catalytic kinase activity, are causal for autosomal recessive early onset Parkinson's disease (PD). Various studies have indicated that the activation of PINK1 could be a useful strategy in treating neurodegenerative diseases such as PD. Herein, we show that the anthelmintic drug niclosamide and its analogues are capable of activating PINK1 in cells via reversible impairment of the mitochondrial membrane potential. Using these compounds, we demonstrate for the first time that the PINK1 pathway is active and detectable in primary neurons...
December 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29225062/systematic-review-of-the-empirical-investigation-of-resources-to-support-decision-making-regarding-brca1-and-brca2-genetic-testing-in-women-with-breast-cancer
#10
REVIEW
Chloe Grimmett, Karen Pickett, Jonathan Shepherd, Karen Welch, Alejandra Recio-Saucedo, Elke Streit, Helen Seers, Anne Armstrong, Ramsey I Cutress, D Gareth Evans, Ellen Copson, Bettina Meiser, Diana Eccles, Claire Foster
OBJECTIVE: Identify existing resources developed and/or evaluated empirically in the published literature designed to support women with breast cancer making decisions regarding genetic testing for BRCA1/2 mutations. METHODS: Systematic review of seven electronic databases. Studies were included if they described or evaluated resources that were designed to support women with breast cancer in making a decision to have genetic counselling or testing for familial breast cancer...
November 26, 2017: Patient Education and Counseling
https://www.readbyqxmd.com/read/29224783/in%C3%A2-vivo-target-gene-activation-via-crispr-cas9-mediated-trans-epigenetic-modulation
#11
Hsin-Kai Liao, Fumiyuki Hatanaka, Toshikazu Araoka, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D O'Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte
Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29222441/robust-rna-based-in-situ-mutation-detection-delineates-colorectal-cancer-subclonal-evolution
#12
Ann-Marie Baker, Weini Huang, Xiao-Ming Mindy Wang, Marnix Jansen, Xiao-Jun Ma, Jeffrey Kim, Courtney M Anderson, Xingyong Wu, Liuliu Pan, Nan Su, Yuling Luo, Enric Domingo, Timon Heide, Andrea Sottoriva, Annabelle Lewis, Andrew D Beggs, Nicholas A Wright, Manuel Rodriguez-Justo, Emily Park, Ian Tomlinson, Trevor A Graham
Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not detect rare subclones. Here, we address these shortfalls by developing and validating BaseScope-a novel mutation-specific RNA in situ hybridization assay. We target common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival colorectal cancer samples to precisely map the spatial and morphological context of mutant subclones...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221462/ethical-frameworks-for-obtaining-informed-consent-in-tumour-profiling-an-evidence-based-case-for-singapore
#13
Yasmin Bylstra, Tamra Lysaght, Jyothi Thrivikraman, Sangeetha Watson, Patrick Tan
BACKGROUND: Genomic profiling of malignant tumours has assisted clinicians in providing targeted therapies for many serious cancer-related illnesses. Although the characterisation of somatic mutations is the primary aim of tumour profiling for treatment, germline mutations may also be detected given the heterogenous origin of mutations observed in tumours. Guidance documents address the return of germline findings that have health implications for patients and their genetic relations...
December 8, 2017: Human Genomics
https://www.readbyqxmd.com/read/29216342/comparison-of-phenotypic-and-wgs-derived-antimicrobial-resistance-profiles-of-salmonella-enterica-serovars-typhi-and-paratyphi
#14
Martin R Day, Michel Doumith, Vivienne Do Nascimento, Satheesh Nair, Philip M Ashton, Claire Jenkins, Timothy J Dallman, Flora J Stevens, Joanne Freedman, Katie L Hopkins, Neil Woodford, Elizabeth M De Pinna, Gauri Godbole
Objectives: Surveillance of antimicrobial resistance (AMR) in Salmonella enterica serovars Typhi and Paratyphi is essential to provide an evidence base for empirical treatment protocols and to monitor emerging AMR. We sought to compare phenotypic and WGS-based genotypic methods for the detection of AMR in Salmonella Typhi and Salmonella Paratyphi. Methods: WGS data from 603 isolates of Salmonella Typhi (n = 332) and Salmonella Paratyphi (n = 271) were mapped to genes or chromosomal mutations known to be associated with phenotypic AMR and compared with phenotypic susceptibility data interpreted using breakpoints recommended by EUCAST...
December 5, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29216315/the-pul37-tegument-protein-guides-alpha-herpesvirus-retrograde-axonal-transport-to-promote-neuroinvasion
#15
Alexsia L Richards, Patricia J Sollars, Jared D Pitts, Austin M Stults, Ekaterina E Heldwein, Gary E Pickard, Gregory A Smith
A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector...
December 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29215048/high-dose-parenteral-ascorbate-inhibited-pancreatic-cancer-growth-and-metastasis-mechanisms-and-a-phase-i-iia-study
#16
Kishore Polireddy, Ruochen Dong, Gregory Reed, Jun Yu, Ping Chen, Stephen Williamson, Pierre-Christian Violet, Ziyan Pessetto, Andrew K Godwin, Fang Fan, Mark Levine, Jeanne A Drisko, Qi Chen
Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits selective cytotoxic effects in cancer cells through peroxide formation. Here, we further revealed its anti-pancreatic cancer mechanisms and conducted a phase I/IIa study to investigate pharmacokinetic interaction between IVC and gemcitabine...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214440/massarray-based-simultaneous-detection-of-hotspot-somatic-mutations-and-recurrent-fusion-genes-in-papillary-thyroid-carcinoma-the-ptc-ma-assay
#17
Chiara Pesenti, Marina Muzza, Carla Colombo, Maria Carla Proverbio, Claudia Farè, Stefano Ferrero, Monica Miozzo, Laura Fugazzola, Silvia Tabano
PURPOSE: We exploited the MassARRAY (MA) genotyping platform to develop the "PTC-MA assay", which allows the simultaneous detection of 13 hotspot mutations, in the BRAF, KRAS, NRAS, HRAS, TERT, AKT1, PIK3CA, and EIF1AX genes, and six recurrent genetic rearrangements, involving the RET and TRK genes in papillary thyroid cancer (PTC). METHODS: The assay was developed using DNA and cDNA from 12 frozen and 11 formalin-fixed paraffin embedded samples from 23 PTC cases, together with positive and negative controls...
December 6, 2017: Endocrine
https://www.readbyqxmd.com/read/29213092/developmental-nonlinearity-drives-phenotypic-robustness
#18
Rebecca M Green, Jennifer L Fish, Nathan M Young, Francis J Smith, Benjamin Roberts, Katie Dolan, Irene Choi, Courtney L Leach, Paul Gordon, James M Cheverud, Charles C Roseman, Trevor J Williams, Ralph S Marcucio, Benedikt Hallgrímsson
Robustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The mechanisms that produce robustness are poorly understood. Nonlinearities are a ubiquitous feature of development that may link variation in development to phenotypic robustness. Here, we manipulate the gene dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate development. We demonstrate that variation in Fgf8 expression has a nonlinear relationship to phenotypic variation, predicting levels of robustness among genotypes...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29212699/rapid-microarray-based-detection-of-rifampicin-isoniazid-and-fluoroquinolone-resistance-in-mycobacterium-tuberculosis-using-a-single-cartridge
#19
Juliane Havlicek, Beatrice Dachsel, Peter Slickers, Sönke Andres, Patrick Beckert, Silke Feuerriegel, Stefan Niemann, Matthias Merker, Ines Labugger
Rapid and robust identification of mutations in Mycobacterium tuberculosis complex (MTBC) strains mediating multidrug and extensively drug-resistant (M/XDR) phenotypes is crucial to combat the MDR tuberculosis (TB) epidemic. Currently available molecular TB drug susceptibility tests are either restricted to single targets/drugs (i.e. Xpert MTB/RIF) or aid the risk of cross-contaminations due to the design limitations of the open platform (i.e. line probe assays).With a good understanding of the technical and commercial boundaries we designed a test cartridge with an introduction of dried reagents, based on an oligonucleotide array, which has the ability to identify MTBC strains resistant to isoniazid, rifampicin and the fluoroquinolones...
December 6, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29212479/a-pilot-systematic-genomic-comparison-of-recurrence-risks-of-hepatitis-b-virus-associated-hepatocellular-carcinoma-with-low-and-high-degree-liver-fibrosis
#20
Seungyeul Yoo, Wenhui Wang, Qin Wang, M Isabel Fiel, Eunjee Lee, Spiros P Hiotis, Jun Zhu
BACKGROUND: Chronic hepatitis B virus (HBV) infection leads to liver fibrosis, which is a major risk factor in hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. The HBV genome can be inserted into the human genome, and chronic inflammation may trigger somatic mutations. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regards to the different degree of liver fibrosis is not clearly understood...
December 7, 2017: BMC Medicine
keyword
keyword
4791
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"