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https://www.readbyqxmd.com/read/28549950/spray-stability-of-self-assembled-filaments-for-delivery
#1
Abdullah Mahmud, Takamasa Harada, Karthikan Rajagopal, David A Christian, Praful Nair, Ryan Murphy, Dennis E Discher
Filamentous viruses are common in nature and efficiently deliver - sometimes via aerosol - genetic material, viral proteins, and other factors to animals and plants. Aerosolization can be a severe physicochemical test of the stability of any filamentous assembly whether it is made from natural polymers such as viral proteins or synthetic polymers. Here, worm-like "filomicelles" that self-assemble in water from amphiphilic block copolymers were investigated as aerosolized delivery vehicles. After spraying and drying, fluorophore-loaded filomicelles that were originally ~10-20μm long could be imaged as 2-5μm long fragments that survived rehydration on natural and artificial surfaces (i...
May 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28548488/a-fluorescent-split-aptamer-for-visualizing-rna-rna-assembly-in-vivo
#2
Khalid K Alam, Kwaku D Tawiah, Matthew F Lichte, David Porciani, Donald H Burke
RNA-RNA assembly governs key biological processes and is a powerful tool for engineering synthetic genetic circuits. Characterizing RNA assembly in living cells often involves monitoring fluorescent reporter proteins, which are at best indirect measures of underlying RNA-RNA hybridization events and are subject to additional temporal and load constraints associated with translation and activation of reporter proteins. In contrast, RNA aptamers that sequester small molecule dyes and activate their fluorescence are increasingly utilized in genetically encoded strategies to report on RNA-level events...
May 26, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28544016/recent-advances-of-crispr-cas9-genome-editing-technologies-for-biological-and-biomedical-investigations
#3
Vijai Singh, Nisarg Gohil, Robert Ramírez García, Darren Braddick, Christian Kuete Fofié
The Type II CRISPR-Cas9 system is a simple, efficient, and versatile tool for targeted genome editing in a wide range of organisms and cell types. It continues to gain more scientific interest and has established itself as an extremely powerful technology within our synthetic biology toolkit. It works upon a targeted site and generates a double strand breaks that become repaired by either the NHEJ or HDR pathway, modifying or permanently replacing the genomic target sequences of interest. These can include viral targets, single-mutation genetic diseases, and multiple-site corrections for wide scale disease states, offering the potential to manage and cure some of mankind's most persistent biomedical menaces...
May 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543657/ethical-principles-process-and-the-work-of-bioethics-commissions
#4
Daniel P Sulmasy
Shortly after the Presidential Commission for the Study of Bioethical Issues was constituted in 2010 and days before the commission members were to join a conference call to discuss possible topics for their deliberation, Craig Venter held a press conference announcing that his lab had created a synthetic chromosome for a species of mycoplasma and had inserted this genetic material into organisms of another species of mycoplasma (the genes of which had been deactivated), transforming the host species into the donor species...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543567/tgr5-contributes-to-hepatic-cystogenesis-in-rodents-with-polycystic-liver-diseases-via-camp-g%C3%AE-s-signaling
#5
Tatyana V Masyuk, Anatoliy I Masyuk, Maria Lorenzo Pisarello, Brynn N Howard, Bing Q Huang, Pui-Yuen Lee, Xavier Fung, Eduard Sergienko, Robert J Ardesky, Thomas Dy Chung, Anthony B Pinkerton, Nicholas F LaRusso
Hepatic cystogenesis in Polycystic Liver Disease (PLD) is associated with increased levels of cAMP in cholangiocytes lining liver cysts. TGR5, a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with PLD. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to: (i) TGR5 agonists [taurolithocholic acid (TLCA), oleanolic acid (OA) and two synthetic compounds]; (ii) a novel TGR5 antagonist (SBI-115); and (iii) a combination of SBI-115 and pasireotide, a somatostatin receptor (SSTR) analog...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543417/toward-public-bioethics
#6
EDITORIAL
Gregory E Kaebnick
This issue of the Hastings Center Report (May-June 2017) features a couple of interesting takes on the governance challenges of emerging technologies. In an essay on the National Academies of Science, Engineering, and Medicine report published this February on human germ-line gene editing, Eric Juengst, a philosopher at the University of North Carolina, argues that the NASEM committee did not manage to rethink the rules. Juengst reaches what he calls an "eccentric conclusion": "The committee's 2017 consensus report has been widely interpreted as 'opening the door' to inheritable human genetic modification and holding a line against enhancement interventions...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28541315/therapeutic-t-cell-engineering
#7
Michel Sadelain, Isabelle Rivière, Stanley Riddell
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28541304/digital-logic-circuits-in-yeast-with-crispr-dcas9-nor-gates
#8
Miles W Gander, Justin D Vrana, William E Voje, James M Carothers, Eric Klavins
Natural genetic circuits enable cells to make sophisticated digital decisions. Building equally complex synthetic circuits in eukaryotes remains difficult, however, because commonly used components leak transcriptionally, do not arbitrarily interconnect or do not have digital responses. Here, we designed dCas9-Mxi1-based NOR gates in Saccharomyces cerevisiae that allow arbitrary connectivity and large genetic circuits. Because we used the chromatin remodeller Mxi1, our gates showed minimal leak and digital responses...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541217/towards-concurrent-data-transmission-exploiting-plasmid-diversity-by-bacterial-conjugation
#9
Bige D Unluturk, M Siblee Islam, Sasitharan Balasubramaniam, Stepan Ivanov
The progress of molecular communication is tightly connected to the progress of nanomachine design. State-of-the-art states that nanomachines can be built either from novel nanomaterials by the help of nanotechnology or they can be built from living cells which are modified to function as intended by synthetic biology. With the growing need of biomedical applications of MC, we focus on developing bio-compatible communication systems by engineering the cells to become MC nanomachines. Since this approach relies on modifying cellular functions, the improvements in the performance can only be achieved by integrating new biological properties...
May 23, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28540598/parp-inhibitors-in-prostate-cancer
#10
REVIEW
Praveen Ramakrishnan Geethakumari, Matthew J Schiewer, Karen E Knudsen, Wm Kevin Kelly
The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded "breakthrough designation" to develop the PARPi olaparib in treating this subset of metastatic PCa patients...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28536286/mutations-that-alter-the-bacterial-cell-envelope-increase-lipid-production
#11
Kimberly C Lemmer, Weiping Zhang, Samantha J Langer, Alice C Dohnalkova, Dehong Hu, Rachelle A Lemke, Jeff S Piotrowski, Galya Orr, Daniel R Noguera, Timothy J Donohue
Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation in Rhodobacter sphaeroides By screening an R. sphaeroides Tn5 mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their total lipids extracellularly...
May 23, 2017: MBio
https://www.readbyqxmd.com/read/28535079/the-tomato-kinase-pti1-contributes-to-production-of-reactive-oxygen-species-in-response-to-two-flagellin-derived-peptides-and-promotes-resistance-to-pseudomonas-syringae-infection
#12
Simon Schwizer, Christine M Kraus, Diane M Dunham, Yi Zheng, Noe Fernandez-Pozo, Marina A Pombo, Zhangjun Fei, Suma Chakravarthy, Gregory Martin
The Pti1 kinase was identified from a reverse genetic screen as contributing to pattern-triggered immunity (PTI) against Pseudomonas syringae pv. tomato (Pst). This was unexpected because Pti1 was originally identified as an interactor of the Pto kinase and was implicated in effector-triggered immunity. The tomato genome has two Pti1 genes, referred to as Pti1a and Pti1b. A hairpin-Pti1 (hpPti1) construct was developed and used to generate two independent stable transgenic tomato lines, which had reduced transcript abundance of both genes...
May 23, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28534601/management-of-psoriatic-arthritis-psa-among-cutaneous-psoriasis-from-pathogenesis-to-therapy
#13
Pauline Hoelt, Cyrille Confavreux, Denis Jullien, Axel P Villani
Psoriatic arthritis (PsA) is an inflammatory rheumatism belonging to spondylarthritis family and which occurs in about 30% of patients with psoriasis. The pathogenesis entails a genetic predisposition, environmental and immunologic factors. Most of the time, cutaneous lesions precede apparition of articular manifestations and dermatologists who treat psoriatic patients have to regularly screen for early PsA, especially in patients with risk factors (notably nail psoriasis). Early detection greatly increases the chances for successful treatment and can prevent slow joint destruction...
May 23, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28527860/biochemical-principles-and-inhibitors-to-interfere-with-viral-capping-pathways
#14
REVIEW
Etienne Decroly, Bruno Canard
Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases ('cap-snatching'). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors...
May 18, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28525770/-expand-and-click-a-new-method-for-labeling-hiv-1-envelope-glycoproteins
#15
Melissa V Fernandez, Eric O Freed
In this issue of Cell Chemical Biology, Sakin et al. (2017) investigate the nanoscale behavior of the HIV-1 envelope (Env) glycoprotein complex by using genetic code expansion, bioorthogonal amino acids, synthetic dyes, and click chemistry. This minimally invasive approach allows the measurement of native Env cellular distribution and dynamics.
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28525263/yellow-and-orange-fluorescent-proteins-with-tryptophan-based-chromophores
#16
Nina G Bozhanova, Mikhail S Baranov, Karen S Sarkisyan, Roman Gritсenko, Konstantin V Mineev, Svetlana V Golodukhina, Nadezhda S Baleeva, Konstantin A Lukyanov, Alexander S Mishin
Rapid development of new microscopy techniques exposed the need for genetically encoded fluorescent tags with special properties. Recent works demonstrated the potential of fluorescent proteins with tryptophan-based chromophores. We applied rational design and random mutagenesis to the monomeric red fluorescent protein FusionRed and found two groups of mutants carrying tryptophan-based chromophore: with yellow (535 nm) or orange (565 nm) emission. On the basis of the properties of proteins, a model synthetic chromophore, and a computational modelling we concluded that the presence of a ketone-containing chromophore in different isomeric forms can explain the observed yellow and orange phenotypes...
May 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28523286/synthetic-lethality-screens-using-rnai-in-combination-with-crispr-based-knockout-in-drosophila-cells
#17
Benjamin E Housden, Hilary E Nicholson, Norbert Perrimon
A synthetic lethal interaction is a type of genetic interaction where the disruption of either of two genes individually has little effect but their combined disruption is lethal. Knowledge of synthetic lethal interactions can allow for elucidation of network structure and identification of candidate drug targets for human diseases such as cancer. In Drosophila, combinatorial gene disruption has been achieved previously by combining multiple RNAi reagents. Here we describe a protocol for high-throughput combinatorial gene disruption by combining CRISPR and RNAi...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28521333/drugging-the-cancers-addicted-to-dna-repair
#18
Jac A Nickoloff, Dennie Jones, Suk-Hee Lee, Elizabeth A Williamson, Robert Hromas
Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality)...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28520786/a-systematic-genetic-screen-for-genes-involved-in-sensing-inorganic-phosphate-availability-in-saccharomyces-cerevisiae
#19
Joonhyuk Choi, Abbhirami Rajagopal, Yi-Fan Xu, Joshua D Rabinowitz, Erin K O'Shea
Saccharomyces cerevisiae responds to changes in extracellular inorganic phosphate (Pi) availability by regulating the activity of the phosphate-responsive (PHO) signaling pathway, enabling cells to maintain intracellular levels of the essential nutrient Pi. Pi-limitation induces upregulation of inositol heptakisphosphate (IP7) synthesized by the inositol hexakisphosphate kinase Vip1, triggering inhibition of the Pho80/Pho85 cyclin-cyclin dependent kinase (CDK) complex by the CDK inhibitor Pho81, which upregulates the PHO regulon through the CDK target and transcription factor Pho4...
2017: PloS One
https://www.readbyqxmd.com/read/28520713/combining-inferred-regulatory-and-reconstructed-metabolic-networks-enhances-phenotype-prediction-in-yeast
#20
Zhuo Wang, Samuel A Danziger, Benjamin D Heavner, Shuyi Ma, Jennifer J Smith, Song Li, Thurston Herricks, Evangelos Simeonidis, Nitin S Baliga, John D Aitchison, Nathan D Price
Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory network models...
May 17, 2017: PLoS Computational Biology
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