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https://www.readbyqxmd.com/read/28202911/what-rheumatologists-need-to-know-about-crispr-cas9
#1
REVIEW
Gary J Gibson, Maozhou Yang
CRISPR/Cas9 genome editing technology has taken the research world by storm since its use in eukaryotes was first proposed in 2012. Publications describing advances in technology and new applications have continued at an unrelenting pace since that time. In this Review, we discuss the application of CRISPR/Cas9 for creating gene mutations - the application that initiated the current avalanche of interest - and new developments that have largely answered initial concerns about its specificity and ability to introduce new gene sequences...
February 9, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28196465/metabolite-toxicity-determines-the-pace-of-molecular-evolution-within-microbial-populations
#2
Elin E Lilja, David R Johnson
BACKGROUND: The production of toxic metabolites has shaped the spatial and temporal arrangement of metabolic processes within microbial cells. While diverse solutions to mitigate metabolite toxicity have evolved, less is known about how evolution itself is affected by metabolite toxicity. We hypothesized that the pace of molecular evolution should increase as metabolite toxicity increases. At least two mechanisms could cause this. First, metabolite toxicity could increase the mutation rate...
February 14, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28192413/evolution-of-a-split-rna-polymerase-as-a-versatile-biosensor-platform
#3
Jinyue Pu, Julia Zinkus-Boltz, Bryan C Dickinson
Biosensors that transduce target chemical and biochemical inputs into genetic outputs are essential for bioengineering and synthetic biology. Current biosensor design strategies are often limited by a low signal-to-noise ratio, the extensive optimization required for each new input, and poor performance in mammalian cells. Here we report the development of a proximity-dependent split RNA polymerase (RNAP) as a general platform for biosensor engineering. After discovering that interactions between fused proteins modulate the assembly of a split T7 RNAP, we optimized the split RNAP components for protein-protein interaction detection by phage-assisted continuous evolution (PACE)...
February 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28185019/biological-ageing-and-clinical-consequences-of-modern-technology
#4
Marios Kyriazis
The pace of technology is steadily increasing, and this has a widespread effect on all areas of health and society. When we interact with this technological environment we are exposed to a wide variety of new stimuli and challenges, which may modulate the stress response and thus change the way we respond and adapt. In this Opinion paper I will examine certain aspects of the human-computer interaction with regards to health and ageing. There are practical, everyday effects which also include social and cultural elements...
February 9, 2017: Biogerontology
https://www.readbyqxmd.com/read/28169001/emerging-approaches-to-tuberculosis-drug-development-at-home-in-the-metabolome
#5
REVIEW
Robert S Jansen, Kyu Y Rhee
Once considered a crowning achievement of modern drug development, tuberculosis (TB) chemotherapy has proven increasingly unable to keep pace with the spread of the pandemic and rise of drug resistance. Efforts to revive the TB drug development pipeline have, in the meantime, faltered. Closer analysis reveals key experimental deficiencies that have hindered our ability to 'reverse engineer' knowledge of antibiotic mechanisms into rational drug development. Here, we discuss the emerging potential of metabolomics; the systems level study of small molecule metabolites, to help overcome these gaps and serve as a unique biochemical bridge between the phenotypic properties of chemical compounds and biological targets...
February 3, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28168672/compilation-of-data-and-modelling-of-nanoparticle-interactions-and-toxicity-in-the-nanopuzzles-project
#6
Andrea-Nicole Richarz, Aggelos Avramopoulos, Emilio Benfenati, Agnieszka Gajewicz, Nazanin Golbamaki Bakhtyari, Georgios Leonis, Richard L Marchese Robinson, Manthos G Papadopoulos, Mark Td Cronin, Tomasz Puzyn
The particular properties of nanomaterials have led to their rapidly increasing use in diverse fields of application. However, safety assessment is not keeping pace and there are still gaps in the understanding of their hazards. Computational models predicting nanotoxicity, such as (quantitative) structure-activity relationships ((Q)SARs), can contribute to safety evaluation, in line with general efforts to apply alternative methods in chemical risk assessment. Their development is highly dependent on the availability of reliable and high quality experimental data, both regarding the compounds' properties as well as the measured toxic effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28148791/replication-capacity-of-viruses-from-acute-infection-drives-hiv-1-disease-progression
#7
Philippe Selhorst, Carina Combrinck, Nonkululeko Ndabambi, Sherazaan D Ismail, Melissa-Rose Abrahams, Miguel Lacerda, Natasha Samsunder, Nigel Garrett, Quarraisha Abdool Karim, Salim S Abdool Karim, Carolyn Williamson
Viral genotype has been shown to play an important role in HIV pathogenesis following transmission. However, the viral phenotypic properties that contribute to disease progression remain unclear. Most studies have been limited to the evaluation of Gag function in the context of a recombinant virus backbone. Using this approach, important biological information may be lost making the evaluation of viruses obtained during acute infection, representing the transmitted virus, a more biologically relevant model...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28148207/clinical-cancer-advances-2017-annual-report-on-progress-against-cancer-from-the-american-society-of-clinical-oncology
#8
Harold J Burstein, Lada Krilov, Jeanny B Aragon-Ching, Nancy N Baxter, E Gabriela Chiorean, Warren Allen Chow, John Frederick De Groot, Steven Michael Devine, Steven G DuBois, Wafik S El-Deiry, Andrew S Epstein, John Heymach, Joshua Adam Jones, Deborah K Mayer, Rebecca A Miksad, Nathan A Pennell, Michael S Sabel, Richard L Schilsky, Lynn Mara Schuchter, Nadine Tung, Karen Marie Winkfield, Lori J Wirth, Don S Dizon
A MESSAGE FROM ASCO'S PRESIDENT I am pleased to present Clinical Cancer Advances 2017, which highlights the most promising advances in patient-oriented cancer research over the past year. The report gives us an opportunity to reflect on what an exciting time it is for cancer research and how swiftly our understanding of cancer has improved. One year ago, the White House announced the national Cancer Moonshot program to accelerate progress against cancer. This shared vision of progress has reinvigorated the research community, identified new areas of scientific collaboration, and raised our ambitions regarding what may be possible beyond the progress we have already made...
February 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28143919/growth-in-prepubertal-children-with-cystic-fibrosis-treated-with-ivacaftor
#9
Michael S Stalvey, Jesse Pace, Minoo Niknian, Mark N Higgins, Valerie Tarn, Joy Davis, Sonya L Heltshe, Steven M Rowe
BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is known for its impact on the lung and pancreas of individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may affect growth outcomes. METHODS: In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6-11 years) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator...
January 31, 2017: Pediatrics
https://www.readbyqxmd.com/read/28137236/the-use-of-the-zebrafish-model-to-aid-in-drug-discovery-and-target-validation
#10
Prusothman Yoganantharjah, Yann Gibert
The zebrafish is fast becoming a leading and prominent model organism used by researchers for developmental biology, and research in modeling human diseases in zebrafish is being undertaken at a fast pace. Many therapeutic areas, including oncology and cardiovascular diseases to name a few all have zebrafish models based on known disease mechanisms that are translatable to modes of action in humans. Many novel assays have been and are continuing to be developed to study human disease in zebrafish. Prominent methods to identify novel drug targets within the organism include, chemical mutagenesis, insertional mutagenesis and high throughput small molecule screens...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28128880/single-cell-proteomics-in-biomedicine-high-dimensional-data-acquisition-visualization-and-analysis
#11
Yapeng Su, Qihui Shi, Wei Wei
New insights on cellular heterogeneity in the last decade provoke the development of a variety of single cell omics tools at a lightning pace. The resultant high-dimensional single cell data generated by these tools require new theoretical approaches and analytical algorithms for effective visualization and interpretation. In this review, we briefly survey the state-of-the-art single cell proteomic tools with a particular focus on data acquisition and quantification, followed by an elaboration of a number of statistical and computational approaches developed to date for dissecting the high-dimensional single cell data...
January 27, 2017: Proteomics
https://www.readbyqxmd.com/read/28125901/onebac-2-0-sf9-cell-lines-for-production-of-aav1-aav2-and-aav8-vectors-with-minimal-encapsidation-of-foreign-dna
#12
Mario Mietzsch, Henrik Hering, Eva-Maria Hammer, Mavis Agbandje-McKenna, Sergei Zolotukhin, Regine Heilbronn
Recombinant adeno-associated viral (rAAV) vectors for human gene therapy require efficient and economical production methods to keep pace with the rapidly increasing clinical demand. In addition, the manufacturing process must ensure high vector quality and biological safety. The OneBac system offers easily scalable rAAV vector production in insect Sf9-derived AAV rep/cap-expressing producer cell lines infected with a single baculovirus that carries the rAAV backbone. For most AAV serotypes high burst sizes per cell were achieved, combined with high infectivity rates...
February 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28114301/weak-synchronization-and-large-scale-collective-oscillation-in-dense-bacterial-suspensions
#13
Chong Chen, Song Liu, Xia-Qing Shi, Hugues Chaté, Yilin Wu
Collective oscillatory behaviour is ubiquitous in nature, having a vital role in many biological processes from embryogenesis and organ development to pace-making in neuron networks. Elucidating the mechanisms that give rise to synchronization is essential to the understanding of biological self-organization. Collective oscillations in biological multicellular systems often arise from long-range coupling mediated by diffusive chemicals, by electrochemical mechanisms, or by biomechanical interaction between cells and their physical environment...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28112075/heterogeneity-in-chronic-fatigue-syndrome-empirically-defined-subgroups-from-the-pace-trial
#14
T E Williams, T Chalder, M Sharpe, P D White
BACKGROUND: Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. METHOD: We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients...
January 23, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28109168/integrated-omics-analysis-of-specialized-metabolism-in-medicinal-plants
#15
Amit Rai, Kazuki Saito, Mami Yamazaki
Medicinal plants are the rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their approach to explore biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. Recent advancements in the high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. Reduced cost to generate omics datasets, and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several plant origin bio-active metabolites...
January 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28102232/aetiology-and-management-of-hereditary-aortopathy
#16
REVIEW
Aline Verstraeten, Ilse Luyckx, Bart Loeys
Aortic aneurysms are a major health problem because they account for 1-2% of all deaths in the Western population. Although abdominal aortic aneurysms (AAAs) are more prevalent than thoracic aortic aneurysms (TAAs), TAAs have been more exhaustively studied over the past 2 decades because they have a higher heritability and affect younger individuals. Gene identification in both syndromic and nonsyndromic TAA is proceeding at a rapid pace and has already pinpointed >20 genes associated with familial TAA risk...
January 19, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28078074/fes-in-europe-and-beyond-current-translational-research
#17
Christine Azevedo Coste, Winfried Mayr, Manfred Bijak, Antonio Musarò, Ugo Carraro
Capacity of adult neural and muscle tissues to respond to external Electrical Stimulation (ES) is the biological basis for the development and implementation of mobility impairment physiotherapy protocols and of related assistive technologies, e.g, Functional Electrical Stimulation (FES). All body tissues, however, respond to electrical stimulation and, indeed, the most successful application of FES is electrical stimulation of the heart to revert or limit effects of arrhythmias (Pace-makers and Defibrillators)...
September 15, 2016: European Journal of Translational Myology
https://www.readbyqxmd.com/read/28076851/pse-analysis-a-python-package-for-dna-rna-and-protein-peptide-sequence-analysis-based-on-pseudo-components-and-kernel-methods
#18
Bin Liu, Hao Wu, Deyuan Zhang, Xiaolong Wang, Kuo-Chen Chou
To expedite the pace in conducting genome/proteome analysis, we have developed a Python package called Pse-Analysis. The powerful package can automatically complete the following five procedures: (1) sample feature extraction, (2) optimal parameter selection, (3) model training, (4) cross validation, and (5) evaluating prediction quality. All the work a user needs to do is to input a benchmark dataset along with the query biological sequences concerned. Based on the benchmark dataset, Pse-Analysis will automatically construct an ideal predictor, followed by yielding the predicted results for the submitted query samples...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28045901/zika-virus-infection-as-a-cause-of-congenital-brain-abnormalities-and-guillain-barr%C3%A3-syndrome-systematic-review
#19
Fabienne Krauer, Maurane Riesen, Ludovic Reveiz, Olufemi T Oladapo, Ruth Martínez-Vega, Teegwendé V Porgo, Anina Haefliger, Nathalie J Broutet, Nicola Low
BACKGROUND: The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28011703/optogenetic-termination-of-ventricular-arrhythmias-in-the-whole-heart-towards-biological-cardiac-rhythm-management
#20
Emile C A Nyns, Annemarie Kip, Cindy I Bart, Jaap J Plomp, Katja Zeppenfeld, Martin J Schalij, Antoine A F de Vries, Daniël A Pijnappels
AIMS: Current treatments of ventricular arrhythmias rely on modulation of cardiac electrical function through drugs, ablation or electroshocks, which are all non-biological and rather unspecific, irreversible or traumatizing interventions. Optogenetics, however, is a novel, biological technique allowing electrical modulation in a specific, reversible and trauma-free manner using light-gated ion channels. The aim of our study was to investigate optogenetic termination of ventricular arrhythmias in the whole heart...
December 23, 2016: European Heart Journal
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