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https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#1
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28640841/a-sorghum-sorghum-bicolor-mutant-with-altered-carbon-isotope-ratio
#2
Govinda Rizal, Shanta Karki, Vivek Thakur, Samart Wanchana, Hugo Alonso-Cantabrana, Jacque Dionora, John E Sheehy, Robert Furbank, Susanne von Caemmerer, William Paul Quick
Recent efforts to engineer C4 photosynthetic traits into C3 plants such as rice demand an understanding of the genetic elements that enable C4 plants to outperform C3 plants. As a part of the C4 Rice Consortium's efforts to identify genes needed to support C4 photosynthesis, EMS mutagenized sorghum populations were generated and screened to identify genes that cause a loss of C4 function. Stable carbon isotope ratio (δ13C) of leaf dry matter has been used to distinguishspecies with C3 and C4 photosynthetic pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28637421/a-novel-pathway-based-distance-score-enhances-assessment-of-disease-heterogeneity-in-gene-expression
#3
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
https://www.readbyqxmd.com/read/28633360/expression-properties-exhibit-correlated-patterns-with-the-fate-of-duplicated-genes-their-divergence-and-transcriptional-plasticity-in-saccharomycotina
#4
Florian Mattenberger, Beatriz Sabater-Muñoz, Christina Toft, Gaurav Sablok, Mario A Fares
Gene duplication is an important source of novelties and genome complexity. What genes are preserved as duplicated through long evolutionary times can shape the evolution of innovations. Identifying factors that influence gene duplicability is therefore an important aim in evolutionary biology. Here, we show that in the yeast Saccharomyces cerevisiae the levels of gene expression correlate with gene duplicability, its divergence, and transcriptional plasticity. Genes that were highly expressed before duplication are more likely to be preserved as duplicates for longer evolutionary times and wider phylogenetic ranges than genes that were lowly expressed...
June 15, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28627704/matrix-metalloproteinase-2-and-9-contribute-to-functional-integrity-and-noise%C3%A2-induced-damage-to-the-blood-labyrinth-barrier
#5
Jun Wu, Weiju Han, Xingrui Chen, Weiwei Guo, Ke Liu, Ruoya Wang, Jishuai Zhang, Na Sai
The cochlear blood-labyrinth barrier (BLB), located in the stria vascularis, is critical for the homeostasis of cochlear solutes and ion transport. Significant disruption to the BLB occurs early during noise‑induced hearing loss. Matrix metalloproteinase (MMP)‑2 and ‑9 are important molecules known to be capable of degrading tight junction (TJ) proteins. The TJ proteins are important components of the extracellular matrix (ECM), required to maintain BLB integrity and permeability. Previous studies have demonstrated that MMP‑2 and ‑9, rich in healthy cochlea, serve an essential role in regulating the cochlear response to acoustic trauma...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28620411/vicar-an-adaptive-and-landmark-free-registration-of-time-lapse-image-data-from-microfluidics-experiments
#6
Georges Hattab, Jan-Philip Schlüter, Anke Becker, Tim W Nattkemper
In order to understand gene function in bacterial life cycles, time lapse bioimaging is applied in combination with different marker protocols in so called microfluidics chambers (i.e., a multi-well plate). In one experiment, a series of T images is recorded for one visual field, with a pixel resolution of 60 nm/px. Any (semi-)automatic analysis of the data is hampered by a strong image noise, low contrast and, last but not least, considerable irregular shifts during the acquisition. Image registration corrects such shifts enabling next steps of the analysis (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28618495/robustness-of-synthetic-oscillators-in-growing-and-dividing-cells
#7
Joris Paijmans, David K Lubensky, Pieter Rein Ten Wolde
Synthetic biology sets out to implement new functions in cells, and to develop a deeper understanding of biological design principles. Elowitz and Leibler [Nature (London) 403, 335 (2000)NATUAS0028-083610.1038/35002125] showed that by rational design of the reaction network, and using existing biological components, they could create a network that exhibits periodic gene expression, dubbed the repressilator. More recently, Stricker et al. [Nature (London) 456, 516 (2008)NATUAS0028-083610.1038/nature07389] presented another synthetic oscillator, called the dual-feedback oscillator, which is more stable...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28606108/detection-of-gene-environment-interactions-in-the-presence-of-linkage-disequilibrium-and-noise-by-using-genetic-risk-scores-with-internal-weights-from-elastic-net-regression
#8
Anke Hüls, Katja Ickstadt, Tamara Schikowski, Ursula Krämer
BACKGROUND: For the analysis of gene-environment (GxE) interactions commonly single nucleotide polymorphisms (SNPs) are used to characterize genetic susceptibility, an approach that mostly lacks power and has poor reproducibility. One promising approach to overcome this problem might be the use of weighted genetic risk scores (GRS), which are defined as weighted sums of risk alleles of gene variants. The gold-standard is to use external weights from published meta-analyses. METHODS: In this study, we used internal weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression and thereby provided a method that can be used if there are no external weights available...
June 12, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28595363/more-on-the-best-evolutionary-rate-for-phylogenetic-analysis
#9
Seraina Klopfstein, Tim Massingham, Nick Goldman
The accumulation of genome-scale molecular datasets for non-model taxa brings us ever closer to resolving the tree of life of all living organisms. However, despite the depth of data available, a number of studies that each used thousands of genes have reported conflicting results. The focus of phylogenomic projects must thus shift to more careful experimental design. Even though we still have a limited understanding of what are the best predictors of the phylogenetic informativeness of a gene, there is wide agreement that one key factor is its evolutionary rate; but there is no consensus as to whether the rates derived as optimal in various analytical, empirical, and simulation approaches have any general applicability...
June 8, 2017: Systematic Biology
https://www.readbyqxmd.com/read/28595284/infertility-diagnosis-has-a-significant-impact-on-the-transcriptome-of-developing-blastocysts
#10
Blair R McCallie, Jason C Parks, Darren K Griffin, William B Schoolcraft, Mandy G Katz-Jaffe
STUDY QUESTION: Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF), and unexplained (UE)? SUMMARY ANSWER: The global blastocyst transcriptome was significantly altered in association with a PCO, MF, and UE infertility diagnosis. WHAT IS KNOWN ALREADY: Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during pre-implantation development...
June 8, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28592991/aav-based-dual-reporter-circuit-for-monitoring-cell-signaling-in-living-human-cells
#11
Zhiwen Zhang, Zachary Stickney, Natalie Duong, Kevin Curley, Biao Lu
BACKGROUND: High-throughput methods based on molecular reporters have greatly advanced our knowledge of cell signaling in mammalian cells. However, their ability to monitor various types of cells is markedly limited by the inefficiency of reporter gene delivery. Recombinant adeno-associated virus (AAV) vectors are efficient tools widely used for delivering and expressing transgenes in diverse animal cells in vitro and in vivo. Here we present the design, construction and validation of a novel AAV-based dual-reporter circuit that can be used to monitor and quantify cell signaling in living human cells...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28589853/n-of-1-pathways-mixenrich-advancing-precision-medicine-via-single-subject-analysis-in-discovering-dynamic-changes-of-transcriptomes
#12
Qike Li, A Grant Schissler, Vincent Gardeux, Ikbel Achour, Colleen Kenost, Joanne Berghout, Haiquan Li, Hao Helen Zhang, Yves A Lussier
BACKGROUND: Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28589684/chimeric-rnas-in-cancer-and-normal-physiology
#13
REVIEW
Katarzyna Chwalenia, Loryn Facemire, Hui Li
Traditionally, chimeric RNAs were considered to be exclusive to cancer cells. When occasionally observed in normal samples, they were usually considered to be transcriptional 'noises,' or artifacts due to template switching during the reverse transcription and/or Polymerase chain reaction (PCR) steps of experimentation. However, with the advances being made in next generation sequencing technologies and software tools, as well as the accumulation of new experimental evidences, increasing numbers of chimeric transcripts are being identified in noncancerous tissues and cells...
June 7, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28589536/distinguishing-pathogenic-mutations-from-background-genetic-noise-in-cardiology-the-use-of-large-genome-databases-for-genetic-interpretation
#14
REVIEW
Jonas Ghouse, Morten W Skov, Robert S Bigseth, Gustav Ahlberg, Jørgen K Kanters, Morten S Olesen
Advances in clinical genetic testing has led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation-guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings...
June 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28581725/engineered-control-of-genetic-variability-reveals-interplay-between-quorum-sensing-feedback-regulation-and-biochemical-noise
#15
Yadira Boada, Alejandro Vignoni, Jesus Pico
Stochastic fluctuations in gene expression trigger both beneficial and harmful consequences for cell behavior. Therefore, achieving a desired mean protein expression level while minimizing noise is of interest in many applications, including robust protein production systems in industrial biotechnology. Here we consider a synthetic gene circuit combining intracellular negative feedback and cell-to-cell communication based on quorum sensing. Accounting for both intrinsic and extrinsic noise, stochastic simulations allow us to analyze the capability of the circuit to reduce noise strength as a function of its parameters...
June 5, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28575251/hierarchical-probabilistic-models-for-multiple-gene-variant-associations-based-on-next-generation-sequencing-data
#16
Dimitrios V Vavoulis, Jenny C Taylor, Anna Schuh
Motivation: The identification of genetic variants influencing gene expression (known as expression quantitative trait loci or eQTLs ) is important in unravelling the genetic basis of complex traits. Detecting multiple eQTLs simultaneously in a population based on paired DNA-seq and RNA-seq assays employs two competing types of models: models which rely on appropriate transformations of RNA-seq data (and are powered by a mature mathematical theory), or count-based models , which represent digital gene expression explicitly, thus rendering such transformations unnecessary...
May 31, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28573304/universal-signal-generator-for-dynamic-cell-stimulation
#17
Andreas Piehler, Navid Ghorashian, Ce Zhang, Savaş Tay
Dynamic cell stimulation is a powerful technique for probing gene networks and for applications in stem cell differentiation, immunomodulation and signaling. We developed a robust and flexible method and associated microfluidic devices to generate a wide-range of precisely formulated dynamic chemical signals to stimulate live cells and measure their dynamic response. This signal generator is capable of digital to analog conversion (DAC) through combinatoric selection of discrete input concentrations, and outperforms existing methods by both achievable resolution, dynamic range and simplicity in design...
June 2, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28569207/seed-effect-modeling-improves-the-consistency-of-genome-wide-loss-of-function-screens-and-identifies-synthetic-lethal-vulnerabilities-in-cancer-cells
#18
Alok Jaiswal, Gopal Peddinti, Yevhen Akimov, Krister Wennerberg, Sergey Kuznetsov, Jing Tang, Tero Aittokallio
BACKGROUND: Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity...
June 1, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28566513/recursively-constructing-analytic-expressions-for-equilibrium-distributions-of-stochastic-biochemical-reaction-networks
#19
X Flora Meng, Ania-Ariadna Baetica, Vipul Singhal, Richard M Murray
Noise is often indispensable to key cellular activities, such as gene expression, necessitating the use of stochastic models to capture its dynamics. The chemical master equation (CME) is a commonly used stochastic model of Kolmogorov forward equations that describe how the probability distribution of a chemically reacting system varies with time. Finding analytic solutions to the CME can have benefits, such as expediting simulations of multiscale biochemical reaction networks and aiding the design of distributional responses...
May 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28562070/the-role-of-micrornas-in-environmental-risk-factors-noise-induced-hearing-loss-and-mental-stress
#20
Verónica Miguel, Julia Yue Cui, Lidia Daimiel, Cristina Espinosa-Díez, Carlos Fernandez-Hernando, Terrance J Kavanagh, Santiago Lamas
SIGNIFICANCE: MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on every realm of biomedicine is established and progressively increasing. The impact of environment on human health is enormous. Among environmental risk factors impinging on quality of life are those of chemical nature (toxic chemicals, heavy metals, pollutants, pesticides) as well as those related to everyday life such as exposure to noise or mental and psychosocial stress...
May 31, 2017: Antioxidants & Redox Signaling
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