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https://www.readbyqxmd.com/read/28634346/generating-conditional-gene-knockouts-in-plasmodium-a-toolkit-to-produce-stable-dicre-recombinase-expressing-parasite-lines-using-crispr-cas9
#1
Ellen Knuepfer, Marta Napiorkowska, Christiaan van Ooij, Anthony A Holder
Successful establishment of CRISPR/Cas9 genome editing technology in Plasmodium spp. has provided a powerful tool to transform Plasmodium falciparum into a genetically more tractable organism. Conditional gene regulation approaches are required to study the function of gene products critical for growth and erythrocyte invasion of blood stage parasites. Here we employ CRISPR/Cas9 to facilitate use of the dimerisable Cre-recombinase (DiCre) that is frequently used to mediate the excision and loss of loxP-flanked DNA sequences in a rapamycin controlled manner...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633205/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#2
EDITORIAL
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, Timothy J Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
July 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28632344/a-life-cycle-approach-to-species-barriers
#3
Kerstin Johannesson
What maintains reproductive barriers between closely related species is, of course, of fundamental interest to a closer understanding of the mechanisms that generate new biodiversity. One important dichotomy is to separate barriers evolved from divergent selection over environmental gradients (extrinsic barriers) from barriers caused by incompatibilities between different genetic arrangements that may have evolved in isolation (intrinsic barriers). This dichotomy also reflects an important applied consequence...
July 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28631363/experimental-evolution-of-bacillus-subtilis
#4
REVIEW
Daniel R Zeigler, Wayne L Nicholson
The endospore-forming bacteria have persisted on earth perhaps 3Ga, leveraging the flexibility of their distinctive lifestyle to adapt to a remarkably wide range of environments. This process of adaptation can be investigated through the simple but powerful technique of laboratory evolution. Evolved strains can be analyzed by whole genome sequencing and an array of omics technologies. The intensively studied, genetically tractable endospore-former, Bacillus subtilis, is an ideal subject for laboratory evolution experiments...
June 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28630153/membrane-spanning-%C3%AE-helical-barrels-as-tractable-protein-design-targets
#5
REVIEW
Ai Niitsu, Jack W Heal, Kerstin Fauland, Andrew R Thomson, Derek N Woolfson
The rational (de novo) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28627570/determination-of-bending-rigidity-and-tilt-modulus-of-lipid-membranes-from-real-space-fluctuation-analysis-of-molecular-dynamics-simulations
#6
M Doktorova, D Harries, G Khelashvili
We have recently developed a novel computational methodology (termed RSF for Real-Space Fluctuations) to quantify the bending rigidity and tilt modulus of lipid membranes from real-space analysis of fluctuations in the tilt and splay degrees of freedom as sampled in molecular dynamics (MD) simulations. In this article, we present a comprehensive study that combines results from the application of the RSF method to a wide range of lipid bilayer systems that encompass membranes of different fluidities and sizes, including lipids with saturated and unsaturated lipid tails, single and multi-component lipid systems, as well as non-standard lipids such as the four-tailed cardiolipin...
June 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28624690/toward-a-genetic-tool-development-pipeline-for-host-associated-bacteria
#7
REVIEW
Matthew C Waller, Josef R Bober, Nikhil U Nair, Chase L Beisel
Bacteria reside in externally accessible niches on and in multicellular organisms, often forming mutualistic relationships with their host. Recent studies have linked the composition of these microbial communities with alterations in the host's health, behavior, and development, yet the causative mediators of host-microbiota interactions remain poorly understood. Advances in understanding and engineering these interactions require the development of genetic tools to probe the molecular interactions driving the structure and function of microbial communities as well as their interactions with their host...
June 15, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28624514/bromodomain-containing-proteins-in-prostate-cancer
#8
REVIEW
Alfonso Urbanucci, Ian G Mills
Several oncogenic factors have been involved in prostate cancer progression. However, therapeutic approaches still focus on suppression of androgen receptor (AR) signaling. In fact, whereas the full-length AR incorporates a ligand-binding domain, which has become a drug target for competitive inhibitors, other transcription factors often do not have tractable binding pockets that aid drug development. Consequently drug development efforts have turned to transcription co-regulators, often chromatin-modifying enzymes or factors that bind to epigenetic modifications to chromatin...
June 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28623722/recent-advances-in-synthetic-biology-for-engineering-isoprenoid-production-in-yeast
#9
REVIEW
Claudia E Vickers, Thomas C Williams, Bingyin Peng, Joel Cherry
Isoprenoids (terpenes/terpenoids) have many useful industrial applications, but are often not produced at industrially viable level in their natural sources. Synthetic biology approaches have been used extensively to reconstruct metabolic pathways in tractable microbial hosts such as yeast and re-engineer pathways and networks to increase yields. Here we review recent advances in this field, focusing on central carbon metabolism engineering to increase precursor supply, re-directing carbon flux for production of C10, C15, or C20 isoprenoids, and chemical decoration of high value diterpenoids (C20)...
June 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28622673/exact-algorithms-for-duplication-transfer-loss-reconciliation-with-non-binary-gene-trees
#10
Misagh Kordi, Mukul S Bansal
Duplication-Transfer-Loss (DTL) reconciliation is a powerful method for studying gene family evolution in the presence of horizontal gene transfer. DTL reconciliation seeks to reconcile gene trees with species trees by postulating speciation, duplication, transfer, and loss events. Efficient algorithms exist for finding optimal DTL reconciliations when the gene tree is binary. In practice, however, gene trees are often non-binary due to uncertainty in the gene tree topologies, and DTL reconciliation with non-binary gene trees is known to be NP-hard...
June 1, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28619757/cdk4-6-inhibitors-sensitize-rb-positive-sarcoma-cells-to-wee1-kinase-inhibition-through-reversible-cell-cycle-arrest
#11
Ashleigh M Francis, Angela Alexander, Yanna Liu, Smruthi Vijayaraghavan, Kwang Hui Low, Dong Yang, Tuyen Bui, Neeta Somaiah, Vinod Ravi, Khandan Keyomarsi, Kelly K Hunt
Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28617844/wolbachia-elevates-host-methyltransferase-expression-to-block-an-rna-virus-early-during-infection
#12
Tamanash Bhattacharya, Irene L G Newton, Richard W Hardy
Wolbachia pipientis is an intracellular endosymbiont known to confer host resistance against RNA viruses in insects. However, the causal mechanism underlying this antiviral defense remains poorly understood. To this end, we have established a robust arthropod model system to study the tripartite interaction involving Sindbis virus and Wolbachia strain wMel within its native host, Drosophila melanogaster. By leveraging the power of Drosophila genetics and a parallel, highly tractable D. melanogaster derived JW18 cell culture system, we determined that in addition to reducing infectious virus production, Wolbachia negatively influences Sindbis virus particle infectivity...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28616841/zebrafish-prefer-larger-to-smaller-shoals-analysis-of-quantity-estimation-in-a-genetically-tractable-model-organism
#13
Diane Seguin, Robert Gerlai
Numerical abilities have been demonstrated in a variety of non-human vertebrates. However, underlying biological mechanisms have been difficult to study due to a paucity of experimental tools. Powerful genetic and neurobiological tools already exist for the zebrafish, but numerical abilities remain scarcely explored with this species. Here, we investigate the choice made by single experimental zebrafish between numerically different shoals of conspecifics presented concurrently on opposite sides of the experimental tank...
June 14, 2017: Animal Cognition
https://www.readbyqxmd.com/read/28616166/gregariousness-does-not-vary-with-geography-developmental-stage-or-group-relatedness-in-feeding-redheaded-pine-sawfly-larvae
#14
John W Terbot, Ryan L Gaynor, Catherine R Linnen
Aggregations are widespread across the animal kingdom, yet the underlying proximate and ultimate causes are still largely unknown. An ideal system to investigate this simple, social behavior is the pine sawfly genus Neodiprion, which is experimentally tractable and exhibits interspecific variation in larval gregariousness. To assess intraspecific variation in this trait, we characterized aggregative tendency within a single widespread species, the redheaded pine sawfly (N. lecontei). To do so, we developed a quantitative assay in which we measured interindividual distances over a 90-min video...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28605577/a-toolkit-for-nannochloropsis-oceanica-ccmp1779-enables-gene-stacking-and-genetic-engineering-of-the-eicosapentaenoic-acid-pathway-for-enhanced-long-chain-polyunsaturated-fatty-acid-production
#15
Eric Poliner, Jane A Pulman, Krzysztof Zienkiewicz, Kevin Childs, Christoph Benning, Eva M Farré
Nannochloropsis oceanica is an oleaginous microalga rich in ω3long-chain polyunsaturated fatty acids (LC-PUFAs) content, in the form of eicosapentaenoic acid (EPA). We identified the enzymes involved in LC-PUFA biosynthesis in N. oceanica CCMP1779 and generated multigene expression vectors aiming at increasing LC-PUFA content in vivo. We isolated the cDNAs encoding four fatty acid desaturases (FAD) and determined their function by heterologous expression in S. cerevisiae. To increase the expression of multiple fatty acid desaturases in N...
June 12, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28592988/algorithms-for-computing-the-double-cut-and-join-distance-on-both-gene-order-and-intergenic-sizes
#16
Guillaume Fertin, Géraldine Jean, Eric Tannier
BACKGROUND: Combinatorial works on genome rearrangements have so far ignored the influence of intergene sizes, i.e. the number of nucleotides between consecutive genes, although it was recently shown decisive for the accuracy of inference methods (Biller et al. in Genome Biol Evol 8:1427-39, 2016; Biller et al. in Beckmann A, Bienvenu L, Jonoska N, editors. Proceedings of Pursuit of the Universal-12th conference on computability in Europe, CiE 2016, Lecture notes in computer science, vol 9709, Paris, France, June 27-July 1, 2016...
2017: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/28589101/recombineering-in-streptococcus-mutans-using-direct-repeat-mediated-cloning-independent-markerless-mutagenesis-dr-cimm
#17
Shan Zhang, Zhengzhong Zou, Jens Kreth, Justin Merritt
Studies of the dental caries pathogen Streptococcus mutans have benefitted tremendously from its sophisticated genetic system. As part of our own efforts to further improve upon the S. mutans genetic toolbox, we previously reported the development of the first cloning-independent markerless mutagenesis (CIMM) system for S. mutans and illustrated how this approach could be adapted for use in many other organisms. The CIMM approach only requires overlap extension PCR (OE-PCR) protocols to assemble counterselectable allelic replacement mutagenesis constructs, and thus greatly increased the speed and efficiency with which markerless mutations could be introduced into S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28588524/perceptual-plasticity-for-auditory-object-recognition
#18
Shannon L M Heald, Stephen C Van Hedger, Howard C Nusbaum
In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument), speaking (or playing) rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28587636/recognizing-rna-structural-motifs-in-ht-selex-data-for-ribosomal-protein-s15
#19
Shermin Pei, Betty L Slinger, Michelle M Meyer
BACKGROUND: Proteins recognize many different aspects of RNA ranging from single stranded regions to discrete secondary or tertiary structures. High-throughput sequencing (HTS) of in vitro selected populations offers a large scale method to study RNA-proteins interactions. However, most existing analysis methods require that the binding motifs are enriched in the population relative to earlier rounds, and that motifs are found in a loop or single stranded region of the potential RNA secondary structure...
June 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28586479/advanced-multi-loop-algorithms-for-rna-secondary-structure-prediction-reveal-that-the-simplest-model-is-best
#20
Max Ward, Amitava Datta, Michael Wise, David H Mathews
Algorithmic prediction of RNA secondary structure has been an area of active inquiry since the 1970s. Despite many innovations since then, our best techniques are not yet perfect. The workhorses of the RNA secondary structure prediction engine are recursions first described by Zuker and Stiegler in 1981. These have well understood caveats; a notable flaw is the ad-hoc treatment of multi-loops, also called helical-junctions, that persists today. While several advanced models for multi-loops have been proposed, it seems to have been assumed that incorporating them into the recursions would lead to intractability, and so no algorithms for these models exist...
June 6, 2017: Nucleic Acids Research
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