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Synthetic genetics

Fabíola Araújo, José Filho, Aldebaro Klautau
Voice imitation basically consists in estimating a synthesizer input parameters to mimic a target speech signal. This is a difficult inverse problem because the mapping is time-varying, non-linear and from many to one. It typically requires considerable amount of time to be done manually. This work presents a system based on a genetic algorithm (GA) to automatically estimate the input parameters of the Klatt and HLSyn formant synthesizers using an analysis-by-synthesis process. Results are presented for natural (human-generated) speech for three male speakers...
October 18, 2016: Bio Systems
Szabolcs Makai, László Tamás, Angéla Juhász
Wheat has been cultivated for 10000 years and ever since the origin of hexaploid wheat it has been exempt from natural selection. Instead, it was under the constant selective pressure of human agriculture from harvest to sowing during every year, producing a vast array of varieties. Wheat has been adopted globally, accumulating variation for genes involved in yield traits, environmental adaptation and resistance. However, one small but important part of the wheat genome has hardly changed: the regulatory regions of both the x- and y-type high molecular weight glutenin subunit (HMW-GS) genes, which are alone responsible for approximately 12% of the grain protein content...
2016: Frontiers in Plant Science
Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
Sharon Downes, Darren Kriticos, Hazel Parry, Cate Paull, Nancy Schellhorn, Myron P Zalucki
Helicoverpa armigera is a major pest of agriculture, horticulture and floriculture throughout the old world and recently invaded parts of the new world. We overview of the evolution in thinking about the application of area-wide approaches to assist with its control by the Australian Cotton Industry to highlight important lessons and future challenges to achieving the same in the New World. An over-reliance of broad-spectrum insecticides led to Helicoverpa spp. in Australian cotton rapidly became resistant to DDT, synthetic pyrethroids, organophosphates, carbamates and endosulfan...
October 17, 2016: Pest Management Science
Jimmy Hwang
Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas...
October 2016: Journal of Gastrointestinal Oncology
Xiaojiaoyang Li, Zihang Yuan, Runping Liu, Hozeifa M Hassan, Hang Yang, Rong Sun, Luyong Zhang, Zhenzhou Jiang
Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model...
October 12, 2016: Toxicology and Applied Pharmacology
Jessica G Perez, Jessica C Stark, Michael C Jewett
Cell-free protein synthesis (CFPS) technologies have enabled inexpensive and rapid recombinant protein expression. Numerous highly active CFPS platforms are now available and have recently been used for synthetic biology applications. In this review, we focus on the ability of CFPS to expand our understanding of biological systems and its applications in the synthetic biology field. First, we outline a variety of CFPS platforms that provide alternative and complementary methods for expressing proteins from different organisms, compared with in vivo approaches...
October 14, 2016: Cold Spring Harbor Perspectives in Biology
Ilya A Osterman, Ekaterina S Komarova, Dmitry I Shiryaev, Ilya A Korniltsev, Irina M Khven, Dmitry A Lukyanov, Vadim N Tashlitsky, Marina V Serebryakova, Olga V Efremenkova, Yan A Ivanenkov, Alexey A Bogdanov, Petr V Sergiev, Olga A Dontsova
In order to accelerate drug discovery, a simple, reliable and cost-effective system for high-throughput identification of a potential antibiotic mechanism of action is required. To facilitate such screening of new antibiotics, we created a double reporter system for not only antimicrobial activity detection, but also for simultaneous sorting of potential antimicrobials into those that cause ribosome stalling, and others that induce SOS response due to DNA damage. In this reporter system the red fluorescent protein gene rfp was placed under the control of the SOS-inducible sulA promoter...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Alla Gagarinova, Geordie Stewart, Bahram Samanfar, Sadhna Phanse, Carl A White, Hiroyuki Aoki, Viktor Deineko, Natalia Beloglazova, Alexander F Yakunin, Ashkan Golshani, Eric D Brown, Mohan Babu, Andrew Emili
Bacterial protein synthesis is an essential, conserved, and environmentally responsive process. Yet, many of its components and dependencies remain unidentified. To address this gap, we used quantitative synthetic genetic arrays to map functional relationships among >48,000 gene pairs in Escherichia coli under four culture conditions differing in temperature and nutrient availability. The resulting data provide global functional insights into the roles and associations of genes, pathways, and processes important for efficient translation, growth, and environmental adaptation...
October 11, 2016: Cell Reports
Laurent Potvin-Trottier, Nathan D Lord, Glenn Vinnicombe, Johan Paulsson
Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator, and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them...
October 12, 2016: Nature
A T Branco, L Schilling, K Silkaitis, D K Dowling, B Lemos
Reproduction and aging evolved to be intimately associated. Experimental selection for early-life reproduction drives the evolution of decreased longevity in Drosophila whereas experimental selection for increased longevity leads to changes in reproduction. Although life history theory offers hypotheses to explain these relationships, the genetic architecture and molecular mechanisms underlying reproduction-longevity associations remain a matter of debate. Here we show that mating triggers accelerated mortality in males and identify hundreds of genes that are modulated upon mating in the fruit fly Drosophila melanogaster...
October 12, 2016: Heredity
Ratan Chopra, Gloria Burow, Charles E Simpson, Jennifer Chagoya, Joann Mudge, Mark D Burow
To test the hypothesis that the cultivated peanut species possesses almost no molecular variability, we sequenced a diverse panel of twenty-two Arachis accessions representing Arachis hypogaea botanical classes, A-, B-, and K- genome diploids, a synthetic amphidiploid, and a tetraploid wild species. RNASeq was performed on pools of three tissues and de novo assembly wasperformed. Realignment of individual accession reads to transcripts of the cultivar OLin identified 306,820 bi-allelic SNPs. Among ten naturally occurring tetraploid accessions, 40,382 unique homozygous SNPs were identified in 14,719 contigs...
October 11, 2016: G3: Genes—Genomes—Genetics
S Frutos, J B Jordan, M M Bio, T W Muir, O R Thiel, M Vila-Perelló
An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway...
October 12, 2016: Organic & Biomolecular Chemistry
Lei Wang
The genetic code can be expanded to include unnatural amino acids (Uaas) by engineering orthogonal components involved in protein translation. To be compatible with live cells, side chains of Uaas have been limited to either chemically inert or bio-orthogonal (i.e., nonreactive toward biomolecules) functionalities. To introduce bioreactivity into live systems, the genetic code has recently been engineered to encode a new class of Uaas, the bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled bioreactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems...
October 6, 2016: New Biotechnology
Nebojša Pavlović, Bojan Stanimirov, Momir Mikov
BACKGROUND: The field of bile acid research has become tremendously active. Bile acids have been shown to act as signaling molecules that are involved in many metabolic processes, but their role in carcinogenesis is also emerging. METHODS: The aim of this review was to summarize the present knowledge in the innovative field of bile acids pharmacology, to reveal the novel mechanisms of their action, particularly focusing on clinically relevant aspects, and to evaluate the role of both genetic and epigenetic variation in genes encoding bile acid-activated receptors in determining the therapy outcome...
October 6, 2016: Current Pharmaceutical Design
Martine Devic, Thomas Roscoe
Networks controlling developmental or metabolic processes in plants are often complex as a consequence of the duplication and specialisation of the regulatory genes as well as the numerous levels of transcriptional and post-transcriptional controls added during evolution. Networks serve to accommodate multicellular complexity and increase robustness to environmental changes. Mathematical simplification by regrouping genes or pathways in a limited number of hubs has facilitated the construction of models for complex traits...
November 2016: Plant Science: An International Journal of Experimental Plant Biology
Robin M Murray, Harriet Quigley, Diego Quattrone, Amir Englund, Marta Di Forti
Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high-potency forms of cannabis...
October 2016: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
Eleonora Bellucci, Riccardo Terenzi, Giuliana Maria Concetta La Paglia, Stefano Gentileschi, Alessandra Tripoli, Chiara Tani, Alessia Alunno
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic synovial inflammation leading to joint destruction and bone erosions. Although the pathogenic mechanisms underlying the disease are not fully elucidated, it is known that genetic susceptibility and environmental factors trigger an abnormal autoimmune response. Potentially, any organ and tissue could be affected by RA and the increased cardiovascular (CV) risk represents the major complication responsible for a worse prognosis. In this setting, the shared pathogenic mechanisms between RA pathogenesis and accelerated atherosclerosis further strengthen the rationale for a treat-to-target strategy with synthetic and biologic disease modifying anti-rheumatic drugs...
September 2016: Clinical and Experimental Rheumatology
Shubhendu Palei, Henning D Mootz
Cyclic peptides are highly desired molecules not only for basic research but also for many biomedical and pharmacological applications. Due to their potentially superior physicochemical properties as compared to their linear counterparts, they are considered as ideal candidates for studying protein-protein interactions, among others. Most of the methods developed in recent years to prepare cyclic peptides focus either on a synthetic or a recombinant route. While the former provides access to diversified, noncanonical peptides, including unnatural and D-amino acid, for example, the latter can harness the power of genetic randomization to generate and select from large peptide libraries...
2017: Methods in Molecular Biology
Nevena Cvetesic, Ita Gruic-Sovulj
The covalent coupling of cognate amino acid-tRNA pairs by corresponding aminoacyl-tRNA synthetases (aaRS) defines the genetic code and provides aminoacylated tRNAs for ribosomal protein synthesis. Besides the cognate substrate, some non-cognate amino acids may also compete for tRNA aminoacylation. However, their participation in protein synthesis is generally prevented by an aaRS proofreading activity located in the synthetic site and in a separate editing domain. These mechanisms, coupled with the ability of certain aaRSs to discriminate well against non-cognate amino acids in the synthetic reaction alone, define the accuracy of the aminoacylation reaction...
October 3, 2016: Methods: a Companion to Methods in Enzymology
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