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Directed Evolution

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https://www.readbyqxmd.com/read/28087697/development-of-high-affinity-and-high-specificity-inhibitors-of-metalloproteinase-14-through-computational-design-and-directed-evolution
#1
Valeria Arkadash, Gal Yosef, Jason Shirian, Itay Cohen, Yuval Horev, Moran Grossman, Irit Sagi, Evette S Radisky, Julia M Shifman, Niv Papo
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as three decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28086752/single-genome-retrieval-of-context-dependent-variability-in-mutation-rates-for-human-germline
#2
Aleksandr B Sahakyan, Shankar Balasubramanian
BACKGROUND: Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. RESULTS: The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28078452/do-deer-and-raccoons-defecate-in-the-right-place-fitness-consequences-of-vertebrate-seed-dispersal-for-a-deciduous-forest-herb
#3
Eric C Niederhauser, Glenn R Matlack
Precision of seed placement in a heterogeneous environment is often assumed to select for the evolution of animal-mediated dispersal systems, but this hypothesis has rarely been tested in a multivariate sense. We quantify the microsite fitness benefits of dispersal by white-tailed deer (Odocoileus virginianus) and raccoons (Procyon lotor) for mayapple (Podophyllum peltatum), a shade-tolerant perennial herb, in deciduous forests of southeastern Ohio, USA. Micro-environmental variables were recorded at dung-deposition microsites, at rooting points of mayapple shoots, and at random (control) points in the forest...
January 11, 2017: Oecologia
https://www.readbyqxmd.com/read/28075480/costs-of-selfing-prevent-the-spread-of-a-self-compatibility-mutation-that-causes-reproductive-assurance
#4
Nathan C Layman, M Thilina R Fernando, Christopher R Herlihy, Jeremiah W Busch
In flowering plants, shifts from outcrossing to partial or complete self-fertilization have occurred independently thousands of times, yet the underlying adaptive processes are difficult to discern. Selfing's ability to provide reproductive assurance when pollination is uncertain is an oft-cited ecological explanation for its evolution, but this benefit may be outweighed by genetic costs diminishing its selective advantage over outcrossing. We directly studied the fitness effects of a self-compatibility (SC) mutation that was backcrossed into a self-incompatible (SI) population of Leavenworthia alabamica, illuminating the direction and magnitude of selection on the mating-system modifier...
January 11, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28075479/different-contributions-of-local-and-distant-regulatory-changes-to-transcriptome-divergence-between-stickleback-ecotypes
#5
Asano Ishikawa, Makoto Kusakabe, Kohta Yoshida, Mark Ravinet, Takashi Makino, Atsushi Toyoda, Asao Fujiyama, Jun Kitano
Differential gene expression can play an important role in phenotypic evolution and divergent adaptation. Although differential gene expression can be caused by both local- and distant-regulatory changes, we know little about their relative contribution to transcriptome evolution in natural populations. Here, we conducted expression quantitative trait loci (eQTL) analysis to investigate the genetic architecture underlying transcriptome divergence between marine and stream ecotypes of threespine sticklebacks (Gasterosteus aculeatus)...
January 11, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28075035/direct-observations-of-nanofilament-evolution-in-switching-processes-in-hfo2-based-resistive-random-access-memory-by-in-situ-tem-studies
#6
Chao Li, Bin Gao, Yuan Yao, Xiangxiang Guan, Xi Shen, Yanguo Wang, Peng Huang, Lifeng Liu, Xiaoyan Liu, Junjie Li, Changzhi Gu, Jinfeng Kang, Richeng Yu
Resistive switching processes in HfO2 are studied by electron holography and in situ energy-filtered imaging. The results show that oxygen vacancies are gradually generated in the oxide layer under ramped electrical bias, and finally form several conductive channels connecting the two electrodes. It also shows that the switching process occurs at the top interface of the hafnia layer.
January 11, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28074878/microscopic-evolution-of-laboratory-volcanic-hybrid-earthquakes
#7
H O Ghaffari, W A Griffith, P M Benson
Characterizing the interaction between fluids and microscopic defects is one of the long-standing challenges in understanding a broad range of cracking processes, in part because they are so difficult to study experimentally. We address this issue by reexamining records of emitted acoustic phonon events during rock mechanics experiments under wet and dry conditions. The frequency spectrum of these events provides direct information regarding the state of the system. Such events are typically subdivided into high frequency (HF) and low frequency (LF) events, whereas intermediate "Hybrid" events, have HF onsets followed by LF ringing...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074221/exploring-the-thermostable-properties-of-halohydrin-dehalogenase-from-agrobacterium-radiobacter-ad1-by-a-combinatorial-directed-evolution-strategy
#8
Zhiyun Wu, Wenfeng Deng, Yapei Tong, Qian Liao, Dongmin Xin, Huashun Yu, Juan Feng, Lixia Tang
As a crucial factor for biocatalysts, protein thermostability often arises from a combination of factors that are often difficult to rationalize. In this work, the thermostable nature of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) was systematically explored using a combinatorial directed evolution approach. For this, a mutagenesis library of HheC mutants was first constructed using error-prone PCR with low mutagenesis frequency. After screening approximately 2000 colonies, six mutants with eight mutation sites were obtained...
January 10, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28074108/cellulolytic-robolector-towards-an-automated-high-throughput-screening-platform-for-recombinant-cellulase-expression
#9
Martina Mühlmann, Martin Kunze, Joaquim Ribeiro, Bertram Geinitz, Christian Lehmann, Ulrich Schwaneberg, Ulrich Commandeur, Jochen Büchs
BACKGROUND: Cellulases are key player in the hydrolyzation of cellulose. Unfortunately, this reaction is slow and a bottleneck in the process chain from biomass to intermediates and biofuels due to low activities of the enzymes. To overcome this draw back, a lot of effort is put into the area of protein engineering, to modify these enzymes by directed evolution or rational design. Huge clone libraries are constructed and have to be screened for improved variants. High-throughput screening is the method of choice to tackle this experimental effort, but up to now only a few process steps are adapted to automated platforms and little attention has been turned to the reproducibility of clone rankings...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28073566/mixotrophy-in-the-phototrophic-dinoflagellate-takayama-helix-family-kareniaceae-predator-of-diverse-toxic-and-harmful-dinoflagellates
#10
Hae Jin Jeong, Jin Hee Ok, An Suk Lim, Ji Eun Kwon, So Jin Kim, Sung Yeon Lee
Takayama spp. are phototrophic dinoflagellates belonging to the family Kareniaceae and have caused fish kills in several countries. Understanding their trophic mode and interactions with co-occurring phytoplankton species are critical steps in comprehending their ecological roles in marine ecosystems, bloom dynamics, and dinoflagellate evolution. To investigate the trophic mode and interactions of Takayama spp., the ability of Takayama helix to feed on diverse algal species was examined, and the mechanisms of prey ingestion were determined...
December 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073449/harmful-algal-bloom-forecast-system-for-sw-ireland-part-ii-are-operational-oceanographic-models-useful-in-a-hab-warning-system
#11
Caroline Cusack, Tomasz Dabrowski, Kieran Lyons, Alan Berry, Guy Westbrook, Rafael Salas, Conor Duffy, Glenn Nolan, Joe Silke
This study investigated the application of a three-dimensional physical hydrodynamic model in a harmful algal bloom forecast system for Bantry Bay, southwest Ireland. Modelled oceanographic conditions were studied and used to help understand observed changes in the chemical and biological patterns from the national biotoxins and phytoplankton monitoring program. The study focused on two toxic events in 2013. An upwelling event was predicted by the model prior to the appearance and population increase of potentially toxic diatoms, Pseudo-nitzschia, and associated domoic acid in shellfish...
March 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073398/-candidatus-moeniiplasma-glomeromycotorum-an-endobacterium-of-arbuscular-mycorrhizal-fungi
#12
Mizue Naito, Alessandro Desirò, Jonathan B Gonzalez, Gang Tao, Joseph B Morton, Paola Bonfante, Teresa E Pawlowska
Arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota) are symbionts of most terrestrial plants. They commonly harbour endobacteria of a largely unknown biology, referred to as MRE (Mollicutes/mycoplasma-related endobacteria). Here, we propose to accommodate MRE in the novel genus 'Candidatus Moeniiplasma.' Phylogeny reconstructions based on the 16S rRNA gene sequences cluster 'Ca. Moeniiplasma' with representatives of the class Mollicutes, whereas phylogenies derived from amino acid sequences of 19 genes indicate that it is a discrete lineage sharing ancestry with the members of the family Mycoplasmataceae...
January 10, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28073260/promoting-active-species-generation-by-electrochemical-activation-in-alkaline-media-for-efficient-electrocatalytic-oxygen-evolution-in-neutral-media
#13
Kun Xu, Han Cheng, Linqi Liu, Haifeng Lv, Xiaojun Wu, Changzheng Wu, Yi Xie
In this study, by using dicobalt phosphide nanoparticles as precatalysts, we demonstrated that electrochemical activation of metallic precatalysts in alkaline media (comparing with directly electrochemical activation in neutral media) could significantly promote the OER catalysis in neutral media, specifically realizing a 2-fold enhanced activity and meanwhile showing a greatly decreased overpotential of about 100 mV at 10 mA cm(-2). Compared directly with electrochemical activation in neutral media, the electrochemical activation in harsh alkaline media could easily break the strong Co-Co bond and promote active species generation on the surface of metallic Co2P, thus accounting for the enhancement of neutral OER activity, which is also evidenced by HRTEM and the electrochemical double-layer capacitance measurement...
January 11, 2017: Nano Letters
https://www.readbyqxmd.com/read/28071790/synthesizing-perspectives-on-the-evolution-of-cooperation-within-and-between-species
#14
Jessica L Barker, Judith L Bronstein, Maren L Friesen, Emily I Jones, H Kern Reeve, Andrew G Zink, Megan E Frederickson
Cooperation is widespread both within and between species, but are intra-specific and inter-specific cooperation fundamentally similar or qualitatively different phenomena? This review evaluates this question, necessary for a general understanding of the evolution of cooperation. First, we outline three advantages of cooperation relative to non-cooperation (acquisition of otherwise inaccessible goods and services, more efficient acquisition of resources, and buffering against variability), and predict when individuals should cooperate with a conspecific versus a heterospecific partner to obtain these advantages...
January 10, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28071784/a-continued-role-for-signalling-functions-in-the-early-evolution-of-feathers
#15
Graeme D Ruxton, Walter S Persons, Philip J Currie
Persons and Currie (2015) argued against either flight, thermoregulation, or signalling as a functional benefit driving the earliest evolution of feathers; rather, they favoured simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead towards a signalling, rather than (or in addition to), a thermoregulatory function...
January 10, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28071777/radical-recombination-in-interstellar-ices-a-not-so-simple-mechanism
#16
Teddy Butscher, Fabrice Duvernay, Albert Rimola, Mireia Segado-Centellas, Thierry Chiavassa
Many complex organic molecules (hereafter COMs) have been detected in different regions of the interstellar medium (ISM). In each region, different energetic processes - UV irradiation, atom bombardments, etc. - that could be linked to the formation of detected COMs may occur depending on the environment. Several formation mechanisms were proposed but increasing attention is paid to radical recombination reactions. Previous studies showed that glycolaldehyde (HC(O)CH2OH) and ethylene glycol (HOCH2CH2OH) are formed by radical recombination between HC˙O and ˙CH2OH, and by ˙CH2OH dimerisation, respectively...
January 10, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28071715/in-situ-characterization-of-nanoparticles-using-rayleigh-scattering
#17
Biswajit Santra, Mikhail N Shneider, Roberto Car
We report a theoretical analysis showing that Rayleigh scattering could be used to monitor the growth of nanoparticles under arc discharge conditions. We compute the Rayleigh scattering cross sections of the nanoparticles by combining light scattering theory for gas-particle mixtures with calculations of the dynamic electronic polarizability of the nanoparticles. We find that the resolution of the Rayleigh scattering probe is adequate to detect nanoparticles as small as C60 at the expected concentrations of synthesis conditions in the arc periphery...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071047/linking-load-fuel-and-emission-controls-to-photochemical-production-of-secondary-organic-aerosol-from-a-diesel-engine
#18
Shantanu H Jathar, Beth Friedman, Abril A Galang, Michael F Link, Patrick Brophy, John Volckens, Sailaja Eluri, Delphine K Farmer
Diesel engines are important sources of fine particle pollution in urban environments but their contribution to the atmospheric formation of secondary organic aerosol (SOA) is not well constrained. We investigated direct emissions of primary organic aerosol (POA) and photochemical production of SOA from a diesel engine using an oxidation flow reactor (OFR). In less than a day of simulated atmospheric aging, SOA production exceeded POA emissions by an order of magnitude or more. Efficient combustion at higher engine loads coupled to the removal of SOA precursors and particle emissions by aftertreatment systems reduced POA emission factors by an order of magnitude and SOA production factors by factors of 2-10...
January 10, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28071009/evolution-of-free-amino-acids-biogenic-amines-and-n-nitrosoamines-throughout-ageing-in-organic-fermented-beef
#19
Karolina M Wójciak, Elżbieta Solska
BACKGROUND: In recent years, interest in uncured meat products has grown and studies were carried out on the use of substances which could replace nitrites, such as acid whey. In spite of this problem in fermented meat products, there is no information regarding the effects of prolonged ageing on the formation of chemical (nitrosoamines, biogenic amines, secondary lipid oxidation products) and microbiological (L. monocytogenes, S. aureus, OLD) toxicants in fermented beef marinated with acid whey...
April 2016: Acta Scientiarum Polonorum. Technologia Alimentaria
https://www.readbyqxmd.com/read/28070900/chemoselective-henry-condensations-catalyzed-by-artificial-carboligases
#20
Xavier Garrabou Pi, Duncan Stewart Macdonald, Donald Hilvert
The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in a computationally designed and evolved carboligase, RA95.5-8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme with directed evolution...
January 10, 2017: Chemistry: a European Journal
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