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Computational and Structural Biotechnology Journal

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https://www.readbyqxmd.com/read/27872688/functional-roles-for-exosomal-micrornas-in-the-tumour-microenvironment
#1
REVIEW
Emma Bell, Molly A Taylor
Extracellular microRNAs are released from cells both passively and actively. The presence of these microRNAs in the tumour microenvironment (TME) can significantly impact on the plasticity of cancer cells leading to the promotion of metastatic and angiogenic processes. These extracellular microRNAs can act not only on other cancer cells, but also cells present in the TME, such as immune cells, endothelial cells, fibroblasts, and others acting to subvert the host immune system and drive tumour progression. In this review we highlight the current understanding of both the mechanisms by which microRNAs are released from tumour cells and the downstream functional effects that extracellular microRNAs have on recipient cells...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27872687/determining-the-molecular-pathways-underlying-the-protective-effect-of-non-steroidal-anti-inflammatory-drugs-for-alzheimer-s-disease-a-bioinformatics-approach
#2
Alejo J Nevado-Holgado, Simon Lovestone
Alzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive. In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database) simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin)...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27904714/facilitating-the-commercialization-and-use-of-organ-platforms-generated-by-the-microphysiological-systems-tissue-chip-program-through-public-private-partnerships
#3
REVIEW
Christine A Livingston, Kristin M Fabre, Danilo A Tagle
Microphysiological systems (organs-on-chips, tissue chips) are devices designed to recapitulate human physiology that could be used to better understand drug responses not easily addressed using other in vivo systems or in vitro animal models. Although still in development, initial results seem promising as tissue chips exhibit in vivo systems-like functional responses. The National Center for Advancing Translation Science (NCATS) identifies this technology as a potential tool that could improve the process of getting safer, more effective treatments to patients, and has led to the Tissue Chip Program, which aims to develop, integrate and validate major organ systems for testing...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27872686/engineering-translation-in-mammalian-cell-factories-to-increase-protein-yield-the-unexpected-use-of-long-non-coding-sineup-rnas
#4
REVIEW
Silvia Zucchelli, Laura Patrucco, Francesca Persichetti, Stefano Gustincich, Diego Cotella
Mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27830053/unbiased-mitoproteome-analyses-confirm-non-canonical-rna-expanded-codon-translations
#5
Hervé Seligmann
Proteomic MS/MS mass spectrometry detections are usually biased towards peptides cleaved by experimentally added digestion enzyme(s). Hence peptides resulting from spontaneous degradation and natural proteolysis usually remain undetected. Previous analyses of tryptic human proteome data (cleavage after K, R) detected non-canonical tryptic peptides translated according to tetra- and pentacodons (codons expanded by silent mono- and dinucleotides), and from transcripts systematically (a) deleting mono-, dinucleotides after trinucleotides (delRNAs), (b) exchanging nucleotides according to 23 bijective transformations...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27800126/cryo-electron-microscopy-analysis-of-structurally-heterogeneous-macromolecular-complexes
#6
REVIEW
Slavica Jonić
Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27800125/a-review-on-automatic-analysis-techniques-for-color-fundus-photographs
#7
REVIEW
Renátó Besenczi, János Tóth, András Hajdu
In this paper, we give a review on automatic image processing tools to recognize diseases causing specific distortions in the human retina. After a brief summary of the biology of the retina, we give an overview of the types of lesions that may appear as biomarkers of both eye and non-eye diseases. We present several state-of-the-art procedures to extract the anatomic components and lesions in color fundus photographs and decision support methods to help clinical diagnosis. We list publicly available databases and appropriate measurement techniques to compare quantitatively the performance of these approaches...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27761201/the-promises-of-quantitative-systems-pharmacology-modelling-for-drug%C3%A2-development
#8
V R Knight-Schrijver, V Chelliah, L Cucurull-Sanchez, N Le Novère
Recent growth in annual new therapeutic entity (NTE) approvals by the U.S. Food and Drug Administration (FDA) suggests a positive trend in current research and development (R&D) output. Prior to this, the cost of each NTE was considered to be rising exponentially, with compound failure occurring mainly in clinical phases. Quantitative systems pharmacology (QSP) modelling, as an additional tool in the drug discovery arsenal, aims to further reduce NTE costs and improve drug development success. Through in silico mathematical modelling, QSP can simulate drug activity as perturbations in biological systems and thus understand the fundamental interactions which drive disease pathology, compound pharmacology and patient response...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27761200/catch-me-if-you-can-leukemia-escape-after-cd19-directed-t-cell-immunotherapies
#9
Marco Ruella, Marcela V Maus
Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27721960/zebrafish-small-molecule-screens-taking-the-phenotypic-plunge
#10
Charles H Williams, Charles C Hong
Target based chemical screens are a mainstay of modern drug discovery, but the effectiveness of this reductionist approach is being questioned in light of declines in pharmaceutical R & D efficiency. In recent years, phenotypic screens have gained increasing acceptance as a complementary/alternative approach to early drug discovery. We discuss the various model organisms used in phenotypic screens, with particular focus on zebrafish, which has emerged as a leading model of in vivo phenotypic screens. Additionally, we anticipate therapeutic opportunities, particularly in orphan disease space, in the context of rapid advances in human Mendelian genetics, electronic health record (EHR)-enabled genome-phenome associations, and genome editing...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27708750/classification-and-substrate-head-group-specificity-of-membrane-fatty-acid-desaturases
#11
Dongdi Li, Ruth Moorman, Thomas Vanhercke, James Petrie, Surinder Singh, Colin J Jackson
Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure-function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27642503/evolution-of-biomedical-ontologies-and-mappings-overview-of-recent-approaches
#12
REVIEW
Anika Groß, Cédric Pruski, Erhard Rahm
Biomedical ontologies are heavily used to annotate data, and different ontologies are often interlinked by ontology mappings. These ontology-based mappings and annotations are used in many applications and analysis tasks. Since biomedical ontologies are continuously updated dependent artifacts can become outdated and need to undergo evolution as well. Hence there is a need for largely automated approaches to keep ontology-based mappings up-to-date in the presence of evolving ontologies. In this article, we survey current approaches and novel directions in the context of ontology and mapping evolution...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27635191/mbt-tool-an-open-access-tool-based-on-thermodynamic-electron-equivalents-model-to-obtain-microbial-metabolic-reactions-to-be-used-in-biotechnological-process
#13
Pablo Granda Araujo, Anna Gras, Marta Ginovart
Modelling cellular metabolism is a strategic factor in investigating microbial behaviour and interactions, especially for bio-technological processes. A key factor for modelling microbial activity is the calculation of nutrient amounts and products generated as a result of the microbial metabolism. Representing metabolic pathways through balanced reactions is a complex and time-consuming task for biologists, ecologists, modellers and engineers. A new computational tool to represent microbial pathways through microbial metabolic reactions (MMRs) using the approach of the Thermodynamic Electron Equivalents Model has been designed and implemented in the open-access framework NetLogo...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27602200/disease-models-variants-and-altered-pathways-journeying-rgd-through-the-magnifying-glass
#14
Victoria Petri, G Thomas Hayman, Marek Tutaj, Jennifer R Smith, Stan Laulederkind, Shur-Jen Wang, Rajni Nigam, Jeff De Pons, Mary Shimoyama, Melinda R Dwinell
Understanding the pathogenesis of disease is instrumental in delineating its progression mechanisms and for envisioning ways to counteract it. In the process, animal models represent invaluable tools for identifying disease-related loci and their genetic components. Amongst them, the laboratory rat is used extensively in the study of many conditions and disorders. The Rat Genome Database (RGD-http://rgd.mcw.edu) has been established to house rat genetic, genomic and phenotypic data. Since its inception, it has continually expanded the depth and breadth of its content...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27594979/novel-cell-ess-%C3%A2-supplement-used-as-a-feed-or-as-an-initial-boost-to-cho-serum-free-media-results-in-a-significant-increase-in-protein-yield-and-production
#15
Adam Elhofy
Many metrics, including metabolic profiles, have been used to analyze cell health and optimize productivity. In this study, we investigated the ability of a lipid supplement to increase protein yield. At a concentration of 1% (v/v) the lipid supplement caused a significant increase in protein titer (1118 ± 65.4 ng 10(5) cells(- 1) days(- 1)) when compared to cultures grown in the absence of supplementation (819.3 ± 38.1 ng 10(5) cells(- 1) days(- 1); p < 0.05). This equated to a 37% increase in productivity...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27570613/a-single-use-strategy-to-enable-manufacturing-of-affordable-biologics
#16
REVIEW
Renaud Jacquemart, Melissa Vandersluis, Mochao Zhao, Karan Sukhija, Navneet Sidhu, Jim Stout
The current processing paradigm of large manufacturing facilities dedicated to single product production is no longer an effective approach for best manufacturing practices. Increasing competition for new indications and the launch of biosimilars for the monoclonal antibody market have put pressure on manufacturers to produce at lower cost. Single-use technologies and continuous upstream processes have proven to be cost-efficient options to increase biomass production but as of today the adoption has been only minimal for the purification operations, partly due to concerns related to cost and scale-up...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27570612/antibodies-inside-of-a-cell-can-change-its-outside-can-intrabodies-provide-a-new-therapeutic-paradigm
#17
REVIEW
Andrea L J Marschall, Stefan Dübel
Challenges posed by complex diseases such as cancer, chronic viral infections, neurodegenerative disorders and many others have forced researchers to think beyond classic small molecule drugs, exploring new therapeutic strategies such as therapy with RNAi, CRISPR/Cas9 or antibody therapies as single or as combination therapies with existing drugs. While classic antibody therapies based on parenteral application can only reach extracellular targets, intracellular application of antibodies could provide specific advantages but is so far little recognized in translational research...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27536341/well-characterized-sequence-features-of-eukaryote-genomes-and-implications-for-ab-initio-gene-prediction
#18
REVIEW
Ying Huang, Shi-Yi Chen, Feilong Deng
In silico analysis of DNA sequences is an important area of computational biology in the post-genomic era. Over the past two decades, computational approaches for ab initio prediction of gene structure from genome sequence alone have largely facilitated our understanding on a variety of biological questions. Although the computational prediction of protein-coding genes has already been well-established, we are also facing challenges to robustly find the non-coding RNA genes, such as miRNA and lncRNA. Two main aspects of ab initio gene prediction include the computed values for describing sequence features and used algorithm for training the discriminant function, and by which different combinations are employed into various bioinformatic tools...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27471585/sequence-comparison-molecular-modeling-and-network-analysis-predict-structural-diversity-in-cysteine-proteases-from-the-cape-sundew-drosera-capensis
#19
Carter T Butts, Xuhong Zhang, John E Kelly, Kyle W Roskamp, Megha H Unhelkar, J Alfredo Freites, Seemal Tahir, Rachel W Martin
Carnivorous plants represent a so far underexploited reservoir of novel proteases with potentially useful activities. Here we investigate 44 cysteine proteases from the Cape sundew, Drosera capensis, predicted from genomic DNA sequences. D. capensis has a large number of cysteine protease genes; analysis of their sequences reveals homologs of known plant proteases, some of which are predicted to have novel properties. Many functionally significant sequence and structural features are observed, including targeting signals and occluding loops...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27453772/chimeric-mitochondrial-peptides-from-contiguous-regular-and-swinger-rna
#20
Hervé Seligmann
Previous mass spectrometry analyses described human mitochondrial peptides entirely translated from swinger RNAs, RNAs where polymerization systematically exchanged nucleotides. Exchanges follow one among 23 bijective transformation rules, nine symmetric exchanges (X ↔ Y, e.g. A ↔ C) and fourteen asymmetric exchanges (X → Y → Z → X, e.g. A → C → G → A), multiplying by 24 DNA's protein coding potential. Abrupt switches from regular to swinger polymerization produce chimeric RNAs...
2016: Computational and Structural Biotechnology Journal
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