keyword
MENU ▼
Read by QxMD icon Read
search

Mutational robustness

keyword
https://www.readbyqxmd.com/read/28643015/the-role-of-screening-mri-in-the-era-of-next-generation-sequencing-and-moderate-risk-genetic-mutations
#1
REVIEW
Sarah Macklin, Jennifer Gass, Ghada Mitri, Paldeep S Atwal, Stephanie Hines
With the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, like BRCA1 and BRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, like ATM, CHEK2, and PALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in these genes...
June 22, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28642365/phenotypic-diagnosis-of-lineage-and-differentiation-during-sake-yeast-breeding
#2
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/28640983/multiplexed-crispr-cas9-mediated-metabolic-engineering-of-%C3%AE-aminobutyric-acid-levels-in-solanum-lycopersicum
#3
Rui Li, Ran Li, Xindi Li, Daqi Fu, Benzhong Zhu, Huiqin Tian, Yunbo Luo, Hongliang Zhu
In recent years, the type II CRISPR system has become a widely used and robust technique to implement site-directed mutagenesis in a variety of species including model and crop plants. However, few studies manipulated metabolic pathways in plants using the CRISPR system. Here, we introduced the pYLCRISPR/Cas9 system with one or two single-site guide RNAs to target the tomato phytoene desaturase gene. An obvious albino phenotype was observed in T0 regenerated plants, and more than 61% of the desired target sites were edited...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28640891/baculoviral-delivery-of-crispr-cas9-facilitates-efficient-genome-editing-in-human-cells
#4
Sanne Hindriksen, Arne J Bramer, My Anh Truong, Martijn J M Vromans, Jasmin B Post, Ingrid Verlaan-Klink, Hugo J Snippert, Susanne M A Lens, Michael A Hadders
The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools...
2017: PloS One
https://www.readbyqxmd.com/read/28639197/repurposing-crispr-system-for-transcriptional-activation
#5
Meng Chen, Lei Stanley Qi
In recent years, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has become the most popular one for genome editing. When the nuclease domains of Cas9 protein are mutated into deactivated form (dCas9), CRISPR/dCas9 still retains the ability to bind the targeted DNA sequence, but loses the endonuclease cleavage activity. Taking advantage of the characteristics of this engineered nuclease inactive Cas9, the CRISPR/dCas system has been repurposed into versatile RNA-guided, DNA-targeting platforms, such as genome imaging, gene regulation, and epigenetic modification...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639073/prognostic-factors-affecting-outcomes-in-fistulating-perianal-crohn-s-disease-a-systematic-review
#6
REVIEW
G C Braithwaite, M J Lee, D Hind, S R Brown
BACKGROUND: One in three patients with Crohn's disease will develop a perianal fistulae, and one third of these will achieve long-term healing or closure. A barrier to conducting well-designed clinical trials for these patients is a lack of understanding of prognostic factors. This systematic review sets out to identify factors associated with prognosis of perianal Crohn's fistulae. METHODS: This review was registered on the PROSPERO database (CRD42016050316) and conducted in line with PRISMA guidelines along a predefined protocol...
June 20, 2017: Techniques in Coloproctology
https://www.readbyqxmd.com/read/28637711/the-exon-junction-complex-and-srp54-contribute-to-drosophila-hedgehog-signaling-via-ci-rna-splicing
#7
Elisa Garcia Garcia, Jamie C Little, Daniel Kalderon
Hedgehog (Hh) regulates the Cubitus interruptus (Ci) transcription factor in Drosophila melanogaster by activating full-length Ci-155 and blocking processing to Ci-75 repressor. However, the interplay between regulation of Ci-155 levels and activity, as well as processing-independent mechanisms that affect Ci-155 levels have not been explored extensively. Here we identified Mago Nashi (Mago) and Y14 core Exon Junction Complex (EJC) proteins, as well as the Srp54 splicing factor as modifiers of Hh pathway activity under sensitized conditions...
June 21, 2017: Genetics
https://www.readbyqxmd.com/read/28627419/arx-polyalanine-expansion-mutations-lead-to-migration-impediment-in-the-rostral-cortex-coupled-with-a-developmental-deficit-of-calbindin-positive-cortical-gabaergic-interneurons
#8
K Lee, K Ireland, M Bleeze, C Shoubridge
The Aristaless-related homeobox gene (ARX) is indispensable for interneuron development. Patients with ARX polyalanine expansion mutations of the first two tracts (namely PA1 and PA2) suffer from intellectual disability of varying severity, with seizures a frequent comorbidity. The impact of PA1 and PA2 mutations on the brain development is unknown, hindering the search for therapeutic interventions. Here, we characterized the disturbances to cortical interneuron development in mice modeling the two most common ARX polyalanine expansion mutations in human...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28625696/comparative-visualization-of-the-rna-suboptimal-conformational-ensemble-in%C3%A2-vivo
#9
Chanin T Woods, Lela Lackey, Benfeard Williams, Nikolay V Dokholyan, David Gotz, Alain Laederach
When a ribonucleic acid (RNA) molecule folds, it often does not adopt a single, well-defined conformation. The folding energy landscape of an RNA is highly dependent on its nucleotide sequence and molecular environment. Cellular molecules sometimes alter the energy landscape, thereby changing the ensemble of likely low-energy conformations. The effects of these energy landscape changes on the conformational ensemble are particularly challenging to visualize for large RNAs. We have created a robust approach for visualizing the conformational ensemble of RNAs that is well suited for in vitro versus in vivo comparisons...
June 15, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28623896/with-a-little-help-from-my-friends-cooperation-can-accelerate-the-rate-of-adaptive-valley-crossing
#10
Uri Obolski, Ohad Lewin-Epstein, Eran Even-Tov, Yoav Ram, Lilach Hadany
BACKGROUND: Natural selection favors changes that lead to genotypes possessing high fitness. A conflict arises when several mutations are required for adaptation, but each mutation is separately deleterious. The process of a population evolving from a genotype encoding for a local fitness maximum to a higher fitness genotype is termed an adaptive peak shift. RESULTS: Here we suggest cooperative behavior as a factor that can facilitate adaptive peak shifts. We model cooperation in a public goods scenario, wherein each individual contributes resources that are later equally redistributed among all cooperating individuals...
June 17, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28622374/large-scale-modulation-of-reconstituted-min-protein-patterns-and-gradients-by-defined-mutations-in-mine-s-membrane-targeting-sequence
#11
Simon Kretschmer, Katja Zieske, Petra Schwille
The E. coli MinDE oscillator is a paradigm for protein self-organization and gradient formation. Previously, we reconstituted Min protein wave patterns on flat membranes as well as gradient-forming pole-to-pole oscillations in cell-shaped PDMS microcompartments. These oscillations appeared to require direct membrane interaction of the ATPase activating protein MinE. However, it remained unclear how exactly Min protein dynamics are regulated by MinE membrane binding. Here, we dissect the role of MinE's membrane targeting sequence (MTS) by reconstituting various MinE mutants in 2D and 3D geometries...
2017: PloS One
https://www.readbyqxmd.com/read/28622163/novel-roles-for-mucin-1-in-the-kidney
#12
Mohammad M Al-Bataineh, Rebecca P Hughey
PURPOSE OF REVIEW: Recent studies in the kidney have revealed that the well characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. RECENT FINDINGS: Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance...
June 15, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28620848/cost-effectiveness-of-pembrolizumab-vs-standard-of-care-chemotherapy-as-first-line-treatment-for-metastatic-nsclc-that-expresses-high-levels-of-pd-l1-in-the-united-states
#13
Min Huang, Yanyan Lou, James Pellissier, Thomas Burke, Frank Xiaoqing Liu, Ruifeng Xu, Vamsidhar Velcheti
OBJECTIVES: Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. METHODS: We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years...
June 15, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28615361/targeting-kras-dependent-tumors-with-azd4785-a-high-affinity-therapeutic-antisense-oligonucleotide-inhibitor-of-kras
#14
Sarah J Ross, Alexey S Revenko, Lyndsey L Hanson, Rebecca Ellston, Anna Staniszewska, Nicky Whalley, Sanjay K Pandey, Mitchell Revill, Claire Rooney, Linda K Buckett, Stephanie K Klein, Kevin Hudson, Brett P Monia, Michael Zinda, David C Blakey, Paul D Lyne, A Robert Macleod
Activating mutations in KRAS underlie the pathogenesis of up to 20% of human tumors, and KRAS is one of the most frequently mutated genes in cancer. Developing therapeutics to block KRAS activity has proven difficult, and no direct inhibitor of KRAS function has entered clinical trials. We describe the preclinical evaluation of AZD4785, a high-affinity constrained ethyl-containing therapeutic antisense oligonucleotide (ASO) targeting KRAS mRNA. AZD4785 potently and selectively depleted cellular KRAS mRNA and protein, resulting in inhibition of downstream effector pathways and antiproliferative effects selectively in KRAS mutant cells...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615189/bar-coding-neurodegeneration-identifying-sub-cellular-effects-of-human-neurodegenerative-disease-proteins-using-drosophila-leg-neurons
#15
Josefin Fernius, Annika Starkenberg, Stefan Thor
Genetic, biochemical and histological studies have identified a number of different proteins as key drivers of human neurodegenerative diseases. Whereas different proteins are typically involved in different disease, there is also considerable overlap. Addressing disease protein dysfunction in an in vivo neuronal context is often time-consuming and requires labor-intensive analysis of transgenic models. To facilitate the rapid, cellular analysis of disease protein dysfunction, we have developed a fruit fly (Drosophila melanogaster) adult leg neuron assay...
June 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28612220/individual-outcome-prediction-for-myelodysplastic-syndrome-mds-and-secondary-acute-myeloid-leukemia-from-mds-after-allogeneic-hematopoietic-cell-transplantation
#16
Michael Heuser, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Henriette Kreimeyer, Mira Pankratz, Madita Flintrop, Alessandro Liebich, Sabrina Klesse, Victoria Panagiota, Michael Stadler, Martin Wichmann, Rabia Shahswar, Uwe Platzbecker, Christian Thiede, Thomas Schroeder, Guido Kobbe, Robert Geffers, Brigitte Schlegelberger, Gudrun Göhring, Hans-Heinrich Kreipe, Ulrich Germing, Arnold Ganser, Nicolaus Kröger, Christian Koenecke, Felicitas Thol
We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)...
June 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28611536/germline-mutations-in-triple-negative-breast-cancer
#17
REVIEW
Eric Hahnen, Jan Hauke, Christoph Engel, Guido Neidhardt, Kerstin Rhiem, Rita K Schmutzler
Triple-negative breast cancer (TNBC) is associated with a poor prognosis and defines a subgroup of patients who do not benefit from endocrine or anti-HER2 therapy. Rather than being a biological entity, TNBC represents a heterogeneous disease, and further subtyping is necessary to establish targeted therapies. Germline mutational status may serve as a robust biomarker predicting therapy response, especially with respect to compounds challenging the DNA repair machinery. Patients with TNBC usually show an early onset of the disease, as well as a positive family history of breast and/or ovarian cancer in more than one third of all cases, which suggests that TNBC is closely associated with a hereditary disease cause...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28607805/simplified-microsatellite-instability-detection-protocol-provides-equivalent-sensitivity-to-robust-detection-strategies-in-lynch-syndrome-patients
#18
Hadi Babaei, Mehrdad Zeinalian, Mohammad Hassan Emami, Mortaza Hashemzadeh, Najmeh Farahani, Rasoul Salehi
OBJECTIVE: : Germline mutations in mismatch repair (MMR) genes cause Lynch syndrome (LS). LS is an inherited disease, and an important consequence of MMR deficiency is microsatellite instability (MSI) phenotype. MSI phenotype influences the efficacy of 5 fluorouracil (5-FU) chemotherapy. Reproducible, cost effective, and easy to perform laboratory tests are required to include MSI detection in routine laboratory practice. Evaluation of CAT25 as monomorphic short tandem repeat sequence enables CAT25 to be an efficient screening tool among hereditary nonpolyposis colorectal cancer (HNPCC) patients compared with other methods used currently...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28602104/reproductive-outcome-following-pre-implantation-genetic-diagnosis-pgd-in-the-uk
#19
Abigail Sharpe, Peter Avery, Meenakshi Choudhary
In 2013, the National Health Service Commissioning board centralized the funding in England for up to three cycles of pre-implantation genetic diagnosis (PGD) for couples who have, or are carriers of, a specific genetic disorder. This study presents the historical data of PGD cycles and their clinical outcomes in UK as extrapolated from the national data registry. Retrospective analysis of outcome of cycles undergoing pre-implantation genetic diagnosis in the UK over the past 20 years was performed from the Human Fertilisation and Embryology Authority database (n = 2974)...
June 12, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28600967/mechanisms-of-cell-competition-emerging-from-drosophila-studies
#20
Nicholas E Baker
Cell competition was described in Drosophila as the loss from mosaic tissues of otherwise viable cells heterozygous for Ribosomal protein mutations ('Minutes'). Cell competition has now been described to occur between multiple other genotypes, such as cells differing in myc expression levels, or mutated for neoplastic tumor suppressors. Recent studies implicate innate immunity components, and possibly mechanical stress, compression and cell intercalation as a consequence of differential growth rates in competitive cell death...
June 7, 2017: Current Opinion in Cell Biology
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"