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https://www.readbyqxmd.com/read/28645099/harnessing-the-natural-diversity-and-in-vitro-evolution-of-cas9-to-expand-the-genome-editing-toolbox
#1
REVIEW
Tautvydas Karvelis, Giedrius Gasiunas, Virginijus Siksnys
In the past few years, the Cas9 endonuclease from the type II CRISPR-Cas bacterial antiviral defense system has revolutionized the genome editing field. Guided by an RNA molecule, Cas9 can be reprogrammed to target almost any DNA sequence: the only limitation being the short nucleotide sequence in the vicinity of the target, termed the PAM, which is characteristic for each Cas9 protein. Streptococcus pyogenes Cas9 which recognizes the NGG PAM is currently most widely used for genome manipulation. However, Cas9 orthologues and engineered Cas9 variants offer expanded genome targeting capabilities, improved specificity and biochemical properties...
June 20, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28644828/a-mutant-of-chlamydomonas-without-lhcsr-maintains-high-rates-of-photosynthesis-but-has-reduced-cell-division-rates-in-sinusoidal-light-conditions
#2
Michael Cantrell, Graham Peers
The LHCSR protein belongs to the light harvesting complex family of pigment-binding proteins found in oxygenic photoautotrophs. Previous studies have shown that this complex is required for the rapid induction and relaxation of excess light energy dissipation in a wide range of eukaryotic algae and moss. The ability of cells to rapidly regulate light harvesting between this dissipation state and one favoring photochemistry is believed to be important for reducing oxidative stress and maintaining high photosynthetic efficiency in a rapidly changing light environment...
2017: PloS One
https://www.readbyqxmd.com/read/28644476/enantioselective-intermolecular-benzylic-c-h-amination-catalysed-by-an-engineered-iron-haem-enzyme
#3
Christopher K Prier, Ruijie K Zhang, Andrew R Buller, Sabine Brinkmann-Chen, Frances H Arnold
C-H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C-H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C-H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst-based on a cytochrome P450 monooxygenase-for the highly enantioselective intermolecular amination of benzylic C-H bonds...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#4
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642787/mutational-signatures-are-critical-for-proper-estimation-of-purifying-selection-pressures-in-cancer-somatic-mutation-data-when-using-the-dn-ds-metric
#5
Jimmy Van den Eynden, Erik Larsson
Large cancer genome sequencing initiatives have led to the identification of cancer driver genes based on signals of positive selection in somatic mutation data. Additionally, the identification of purifying (negative) selection has the potential to identify essential genes that may be of therapeutic interest. The most widely used way of quantifying selection pressures in protein-coding genes is the dN/dS metric, which compares non-synonymous to synonymous substitution rates. In this study, we examine whether and how this metric is influenced by the mutational processes that have been active during tumor evolution...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28642345/evolution-of-nonspectral-rhodopsin-function-at-high-altitudes
#6
Gianni M Castiglione, Frances E Hauser, Brian S Liao, Nathan K Lujan, Alexander Van Nynatten, James M Morrow, Ryan K Schott, Nihar Bhattacharyya, Sarah Z Dungan, Belinda S W Chang
High-altitude environments present a range of biochemical and physiological challenges for organisms through decreases in oxygen, pressure, and temperature relative to lowland habitats. Protein-level adaptations to hypoxic high-altitude conditions have been identified in multiple terrestrial endotherms; however, comparable adaptations in aquatic ectotherms, such as fishes, have not been as extensively characterized. In enzyme proteins, cold adaptation is attained through functional trade-offs between stability and activity, often mediated by substitutions outside the active site...
June 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28642229/evolutionary-dynamics-of-the-kinetochore-network-in-eukaryotes-as-revealed-by-comparative-genomics
#7
Jolien Je van Hooff, Eelco Tromer, Leny M van Wijk, Berend Snel, Geert Jpl Kops
During eukaryotic cell division, the sister chromatids of duplicated chromosomes are pulled apart by microtubules, which connect via kinetochores. The kinetochore is a multiprotein structure that links centromeres to microtubules, and that emits molecular signals in order to safeguard the equal distribution of duplicated chromosomes over daughter cells. Although microtubule-mediated chromosome segregation is evolutionary conserved, kinetochore compositions seem to have diverged. To systematically inventory kinetochore diversity and to reconstruct its evolution, we determined orthologs of 70 kinetochore proteins in 90 phylogenetically diverse eukaryotes...
June 22, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28641555/supervised-machine-learning-methods-applied-to-predict-ligand-binding-affinity
#8
Gabriela Sehnem Heck, Val Oliveira Pintro, Richard Rene Pereira, Mauricio Boff de Ávila, Nayara Maria Bernhardt Levin, Walter Filgueira de Azevedo
BACKGROUND: Calculation of ligand-binding affinity is an open problem in computational medicinal chemistry. The ability to computationally predict affinities has a beneficial impact in the early stages of drug development, since it allows a mathematical model to assess protein-ligand interactions. Due to the availability of structural and binding information, machine learning methods have been applied to generate scoring functions with good predictive power. OBJECTIVE: Our goal here is to review recent developments in the application of machine learning methods to predict ligand- binding affinity...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28641482/insights-into-eukaryotic-evolution-from-transmembrane-domain-lengths
#9
Aditya Mittal, Snigdha Singh
Biological membranes, comprised of proteins anchored by their trans-membrane domains (TMDs) creating a semi-permeable phase with lipid constituents, serve as "checkposts" for not only intracellular trafficking in eukaryotic cells but also for material transactions of all living cells with external environments. Hydropathy (or hydrophobicity) plots of "bitopic" proteins (i.e. having single alpha-helical TMDs) are routinely utilized in biochemistry texts for predicting their TMDs. The number of amino acids (i...
June 22, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28640400/little-evidence-for-intralocus-sexual-conflict-over-the-optimal-intake-of-nutrients-for-lifespan-and-reproduction-in-the-black-field-cricket-teleogryllus-commodus
#10
James Rapkin, Ruth C Archer, Charles E Grant, Kim Jensen, Clarissa M House, Alastair J Wilson, John Hunt
There is often large divergence in the effects of key nutrients on lifespan and reproduction in the sexes, yet nutrient intake is regulated in the same way in males and females given dietary choice. This suggests that the sexes are constrained from feeding to their sex-specific nutritional optima for these traits. Here we examine the potential for intralocus sexual conflict (IASC) over optimal protein and carbohydrate intake for lifespan and reproduction to constrain the evolution of sex-specific nutrient regulation in the field cricket, Teleogryllus commodus...
June 22, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28637754/functional-evolution-of-influenza-ns1-protein-in-currently-circulating-human-2009-pandemic-h1n1-viruses
#11
Amelia M Clark, Aitor Nogales, Luis Martinez-Sobrido, David J Topham, Marta L DeDiego
In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist, but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here, we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637420/bioinformatics-insights-on-targets-receptors-of-amiodarone-in-human-and-acanthamoeba-castellanii
#12
Abdul Baig, Zohaib Rana, H R Ahmad
BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in medical practice. The drug targets and inhibits voltage dependent sodium (Na+v), calcium (Ca+2v), potassium (K+v) channels, and enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts anti-amoebic effects against Trypanosoma cruzi and Acanthamoeba castellanii. OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in these pathogenic eukaryotes like Acanthamoeba castellanii remain to be verified...
June 21, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28637337/matrix-completion-with-side-information-and-its-applications-in-predicting-the-antigenicity-of-influenza-viruses
#13
Li Huang, Xianhong Li, Pengfei Guo, Yuhua Yao, Bo Liao, Weiwei Zhang, Fayou Wang, Jiasheng Yang, Yulong Zhao, Hailiang Sun, Pingan He, Jialiang Yang
Motivation: Low-rank matrix completion has been demonstrated to be powerful in predicting antigenic distances among influenza viruses and vaccines from partially revealed hemagglutination inhibition (HI) table. Meanwhile, influenza hemagglutinin (HA) protein sequences are also effective in inferring antigenic distances. Thus, it is natural to integrate HA protein sequence information into low-rank matrix completion model to help infer influenza antigenicity, which is critical to influenza vaccine development...
June 16, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28637261/further-simulations-and-analyses-demonstrate-open-problems-of-phylostratigraphy
#14
Bryan A Moyers, Jianzhi Zhang
Phylostratigraphy, originally designed for gene age estimation by BLAST-based protein homology searches of sequenced genomes, has been widely used for studying patterns and inferring mechanisms of gene origination and evolution. We previously showed by computer simulation that phylostratigraphy underestimates gene age for a non-negligible fraction of genes and that the underestimation is severer for genes with certain properties such as fast evolution and short protein sequences. Consequently, many previously reported age distributions of gene properties may have been methodological artifacts rather than biological realities...
June 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28636881/mitochondrial-genome-of-helice-tientsinensis-brachyura-grapsoidea-varunidae-gene-rearrangements-and-higher-level-phylogeny-of-the-brachyura
#15
Zhao-Zhe Xin, Yu-Liu, Dai-Zhen Zhang, Zheng-Fei Wang, Hua-Bin Zhang, Bo-Ping Tang, Chun-Lin Zhou, Xin-Yue Chai, Qiu-Ning Liu
The mitochondrial genome (mt genome) provides important information for understanding molecular evolution and phylogeny. The further understand the molecular evolution and phylogeny of Helice tientsinensis, the complete mt genome was determined. It is 16,212bp long and includes 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes and a control region. The genome composition of H. tientsinensis was highly A+T biased 69.0% and showed negative AT skew (-0.017) and GC skew (-0.289). One PCG, all rRNAs and 12 of the tRNAs appeared to be rearranged with respect to the pancrustacean ground pattern gene order...
June 18, 2017: Gene
https://www.readbyqxmd.com/read/28636368/probing-the-mechanism-of-lal-32-a-gold-nanoparticle-based-antibiotic-discovered-through-small-molecule-variable-ligand-display
#16
Rose Byrne-Nash, Danielle Lucero, Niki Osbaugh, Roberta J Melander, Christian Melander, Daniel L Feldheim
The unrelenting rise of antimicrobial resistant bacteria has necessitated the search for novel antibiotic solutions. Herein we describe further mechanistic studies on a 2.0 nm diameter gold nanoparticle-based antibiotic (designated LAL-32). This antibiotic exhibits bactericidal activity against the Gram-negative bacterium Escherichia coli at 1.0 μΜ, a concentration significantly lower than several clinically available antibiotics (such as ampicillin and gentamicin), and acute treatment with LAL-32 does not give rise to spontaneous resistant mutants...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#17
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636213/distribution-and-hypoxia-regulation-of-haemocyanin-in-springtails-collembola
#18
S Flachsbarth, M Kruse, T Burmester
Haemocyanin is the copper-containing respiratory protein present in many arthropods. In the hexapods, respiratory proteins had long been considered unnecessary as sufficient O2 was thought to be obtained via the trachea. Nevertheless, many ametabolous and hemimetabolous hexapod species actually possess haemocyanin. Here we investigated the occurrence of haemocyanin in Collembola (springtails). Haemocyanin was found in 22 collembolan species of the suborders Symphypleona, Tomoceroidea and Entomobryomorpha, demonstrating its widespread occurrence...
June 21, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28635657/selection-of-nucleic-acid-aptamers-targeting-tumor-cell-surface-protein-biomarkers
#19
REVIEW
Marie-Cécile Mercier, Monique Dontenwill, Laurence Choulier
Aptamers are nucleic acids referred to as chemical antibodies as they bind to their specific targets with high affinity and selectivity. They are selected via an iterative process known as 'selective evolution of ligands by exponential enrichment' (SELEX). Aptamers have been developed against numerous cancer targets and among them, many tumor cell-membrane protein biomarkers. The identification of aptamers targeting cell-surface proteins has mainly been performed by two different strategies: protein- and cell-based SELEX, when the targets used for selection were proteins and cells, respectively...
June 21, 2017: Cancers
https://www.readbyqxmd.com/read/28635591/camoptimus-a-tool-for-exploiting-complex-adaptive-evolution-to-optimize-experiments-and-processes-in-biotechnology
#20
Ayca Cankorur-Cetinkaya, Joao M L Dias, Jana Kludas, Nigel K H Slater, Juho Rousu, Stephen G Oliver, Duygu Dikicioglu
Multiple interacting factors affect the performance of engineered biological systems in synthetic biology projects. The complexity of these biological systems means that experimental design should often be treated as a multiparametric optimization problem. However, the available methodologies are either impractical, due to a combinatorial explosion in the number of experiments to be performed, or are inaccessible to most experimentalists due to the lack of publicly available, user-friendly software. Although evolutionary algorithms may be employed as alternative approaches to optimize experimental design, the lack of simple-to-use software again restricts their use to specialist practitioners...
June 21, 2017: Microbiology
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