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https://www.readbyqxmd.com/read/28543738/crispr-editing-in-biological-and-biomedical-investigation
#1
Xing-Da Ju, Jing Xu, Zhong Sheng Sun
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR--associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543411/crowdsourcing-the-moral-limits-of-human-gene-editing
#2
Eric T Juengst
In 2015, a flourish of "alarums and excursions" by the scientific community propelled CRISPR/Cas9 and other new gene-editing techniques into public attention. At issue were two kinds of potential gene-editing experiments in humans: those making inheritable germ-line modifications and those designed to enhance human traits beyond what is necessary for health and healing. The scientific consensus seemed to be that while research to develop safe and effective human gene editing should continue, society's moral uncertainties about these two kinds of experiments needed to be better resolved before clinical trials of either type should be attempted...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28542279/oligopeptides-as-full-length-new-delhi-metallo-%C3%AE-lactamase-1-ndm-1-inhibitors
#3
Bingzheng Shen, Chengliang Zhu, Xiang Gao, Gang Liu, Jinchun Song, Yan Yu
'Superbug' bacteria producing NDM-1 enzyme causing wide public concern were first detected in a patient who visited India in 2008. It's an effective approach to combining β-lactam antibiotics with NDM-1 inhibitor for treating NDM-1 producing strain infection. In our research, we designed ten oligopeptides, tested IC50 values against NDM-1 enzyme, determined the MIC values of synergistic antibacterial effect and explored the binding model. We found that the oligopeptides 2 (Cys-Phe) and 5 (Cys-Asp) respectively presented IC50 values of 113 μM and 68 μM and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E...
2017: PloS One
https://www.readbyqxmd.com/read/28540926/entorhinal-cortical-deep-brain-stimulation-rescues-memory-deficits-in-both-young-and-old-mice-genetically-engineered-to-model-alzheimer-s-disease
#4
Frances Xia, Adelaide Yiu, Scellig Sd Stone, Soojin Oh, Andres M Lozano, Sheena A Josselyn, Paul W Frankland
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Deep brain stimulation (DBS) has been used to treat a variety of brain disorders and shows promise in alleviating cognitive symptoms in some AD patients (Laxton et al., 2010). We previously showed that DBS of the entorhinal cortex (EC) enhances spatial memory formation in normal (wild-type) mice (Stone et al., 2011). Here we tested the effects of EC-DBS on the progressive cognitive deficits in a genetically-based mouse model of AD...
May 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28536562/use-of-wild-type-or-recombinant-lactic-acid-bacteria-as-an-alternative-treatment-for-gastrointestinal-inflammatory-diseases-a-focus-on-inflammatory-bowel-diseases-and-mucositis
#5
REVIEW
Rodrigo D De Oliveira Carvalho, Fillipe L R do Carmo, Alberto de Oliveira Junior, Philippe Langella, Jean-Marc Chatel, Luis G Bermúdez-Humarán, Vasco Azevedo, Marcela S de Azevedo
The human gastrointestinal tract (GIT) is highly colonized by bacterial communities, which live in a symbiotic relationship with the host in normal conditions. It has been shown that a dysfunctional interaction between the intestinal microbiota and the host immune system, known as dysbiosis, is a very important factor responsible for the development of different inflammatory conditions of the GIT, such as the idiopathic inflammatory bowel diseases (IBD), a complex and multifactorial disorder of the GIT. Dysbiosis has also been implicated in the pathogenesis of other GIT inflammatory diseases such as mucositis usually caused as an adverse effect of chemotherapy...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28534616/microbes-and-the-next-nitrogen-revolution
#6
Ilje Pikaar, Silvio Matassa, Korneel Rabaey, Benjamin Leon Bodirsky, Alexander Popp, Mario Herrero, Willy Verstraete
The Haber Bosch process is among the greatest inventions of the 20th century. It provided agriculture with reactive nitrogen and ultimately mankind with nourishment for a population of 7 billion people. However, the present agricultural practice of growing crops for animal production and human food constitutes a major threat to the sustainability of the planet in terms of reactive nitrogen pollution. In view of the shortage of directly feasible and cost-effective measures to avoid these planetary nitrogen burdens and the necessity to remediate this problem, we foresee the absolute need for, and expect, a revolution in the use of microbes as a source of protein...
May 23, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28532790/a-safe-and-molecular-tagged-brucella-canis-ghosts-confers-protection-against-virulent-challenge-in-mice
#7
Jing Qian, Zhaoyang Bu, Xulong Lang, Guangmou Yan, Yanling Yang, Xiuran Wang, Xinglong Wang
Canine brucellosis, caused by Brucella canis, is a persistent infectious reproductive disease in dogs. The absence of effective treatment to the intracellular pathogen and the irreversible consequence of infection makes the need of a specific vaccine urgent. Bacterial ghosts (BGs) are the empty envelopes of bacteria with no genome content inside, which emerge as a proper vaccine candidate due to its intact outer antigen. It is generally derived from a genetically engineered strain, through the expression of Bacteriophage phiX174 lysis E gene upon induction...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28531117/immunobiology-of-newcastle-disease-virus-and-its-use-for-prophylactic-vaccination-in-poultry-and-as-adjuvant-for-therapeutic-vaccination-in-cancer-patients
#8
REVIEW
Volker Schirrmacher
Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastledisease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28530655/a-quantitative-and-multiplexed-approach-to-uncover-the-fitness-landscape-of-tumor-suppression-in-vivo
#9
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang, Dmitri Petrov, Monte M Winslow
Cancer growth is a multistage, stochastic evolutionary process. While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. Conventional genetically engineered mouse models enable the study of tumor growth in vivo, but they are neither readily scalable nor sufficiently quantitative to unravel the magnitude and mode of action of many tumor-suppressor genes. Here, we present a method that integrates tumor barcoding with ultradeep barcode sequencing (Tuba-seq) to interrogate tumor-suppressor function in mouse models of human cancer...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28527491/development-of-live-attenuated-bacterial-vaccines-targeting-escherichia-coli-heat-labile-and-heat-stable-enterotoxins
#10
Chengru Zhu, Prashanth Setty, Edgar C Boedeker
Enterotoxigenic Escherichia coli (ETEC), defined by the production of heat labile (LT) and/or heat stable (ST) toxins, are major causes of diarrhea in animals, children in developing countries and to travelers. No broadly protective ETEC vaccine is available, largely because of the difficulty in inducing immunity to the small ST molecule. To take advantage of the demonstration (Liu et al., 2011; Zhang et al., 2013, 2010) that genetically produced fusions of mutant ST with LT subunits can induce effective immunity against both toxins, we engineered a live attenuated vaccine vector strain of E...
April 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28521297/human-menstrual-blood-derived-mesenchymal-stem-cells-as-a-cellular-vehicle-for-malignant-glioma-gene-therapy
#11
Xiao-Jun Wang, Bing-Yu Xiang, Ya-Hui Ding, Lu Chen, Hai Zou, Xiao-Zhou Mou, Charlie Xiang
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28518114/preparation-and-in-vitro-characterization-of-magnetized-mir-modified-endothelial-cells
#12
Natalia Voronina, Heiko Lemcke, Frank Wiekhorst, Jens-Peter Kühn, Markus Frank, Gustav Steinhoff, Robert David
To date, the available surgical and pharmacological treatments for cardiovascular diseases (CVD) are limited and often palliative. At the same time, gene and cell therapies are highly promising alternative approaches for CVD treatment. However, the broad clinical application of gene therapy is greatly limited by the lack of suitable gene delivery systems. The development of appropriate gene delivery vectors can provide a solution to current challenges in cell therapy. In particular, existing drawbacks, such as limited efficiency and low cell retention in the injured organ, could be overcome by appropriate cell engineering (i...
May 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516000/role-of-a-dual-splicing-and-amino-acid-code-in-myopia-cone-dysfunction-and-cone-dystrophy-associated-with-l-m-opsin-interchange-mutations
#13
Scott H Greenwald, James A Kuchenbecker, Jessica S Rowlan, Jay Neitz, Maureen Neitz
PURPOSE: Human long (L) and middle (M) wavelength cone opsin genes are highly variable due to intermixing. Two L/M cone opsin interchange mutants, designated LIAVA and LVAVA, are associated with clinical diagnoses, including red-green color vision deficiency, blue cone monochromacy, cone degeneration, myopia, and Bornholm Eye Disease. Because the protein and splicing codes are carried by the same nucleotides, intermixing L and M genes can cause disease by affecting protein structure and splicing...
May 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28514897/biomaterials-and-bioactive-agents-in-spinal-fusion
#14
Rui M Duarte, Pedro Varanda, Rui L Reis, Ana Rita C Duarte, Jorge Correia-Pinto
Management of degenerative spine pathologies frequently leads to the need for spinal fusion, where bone growth is induced towards stabilization of the interventioned spine. Autologous bone graft (ABG) remains the gold standard inducer, while new bone graft substitutes attempt to achieve effective de novo bone formation and solid fusion. Limited fusion outcomes have driven motivation for more sophisticated and multidisciplinary solutions, involving new biomaterials and/or biologics, through innovative delivery platforms...
May 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28505306/secretion-of-2-3-dihydroxyisovalerate-as-a-limiting-factor-for-isobutanol-production-in-saccharomyces-cerevisiae
#15
Wesley Cardoso Generoso, Martin Brinek, Heiko Dietz, Mislav Oreb, Eckhard Boles
Isobutanol is a superior biofuel compared to ethanol, and it is naturally produced by yeasts. Previously, Saccharomyces cerevisiae has been genetically engineered to improve isobutanol production. We found that yeast cells engineered for a cytosolic isobutanol biosynthesis secrete large amounts of the intermediate 2,3-dihydroxyisovalerate (DIV). This indicates that the enzyme dihydroxyacid dehydratase (Ilv3) is limiting the isobutanol pathway and/or yeast exhibit effective transport systems for the secretion of the intermediate, competing with isobutanol synthesis...
May 12, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28504657/engineering-liposomal-nanoparticles-for-targeted-gene-therapy
#16
REVIEW
C Zylberberg, K Gaskill, S Pasley, S Matosevic
Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection...
May 15, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28503153/investigating-engineered-ribonucleoprotein-particles-to-improve-oral-rnai-delivery-in-crop-insect-pests
#17
François-Xavier Gillet, Rayssa A Garcia, Leonardo L P Macedo, Erika V S Albuquerque, Maria C M Silva, Maria F Grossi-de-Sa
Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil (Anthonomus grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28500672/telomere-length-and-fetal-programming-a-review-of-recent-scientific-advances
#18
Valerie E Whiteman, Anjali Goswami, Hamisu M Salihu
We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication...
May 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28495315/accelerated-mass-production-of-influenza-virus-seed-stocks-in-hek-293-suspension-cell-cultures-by-reverse-genetics
#19
Ernest Milián, Thomas Julien, Rafael Biaggio, Alina Venereo-Sanchez, Johnny Montes, Aziza P Manceur, Sven Ansorge, Emma Petiot, Manuel Rosa-Calatrava, Amine Kamen
Despite major advances in developing capacities and alternative technologies to egg-based production of influenza vaccines, responsiveness to an influenza pandemic threat is limited by the time it takes to generate a Candidate Vaccine Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled "Influenza Vaccine Response during the Start of a Pandemic". In previous work, we have shown that HEK-293 cell culture in suspension and serum free medium is an efficient production platform for cell culture manufacturing of influenza candidate vaccines...
May 8, 2017: Vaccine
https://www.readbyqxmd.com/read/28494742/potential-gene-therapy-towards-treating-neurodegenerative-diseases-employing-polymeric-nanosystems
#20
Prachi Bangde, Sonal Atale, Anomitra Dey, Ashish Pandit, Prajakta Dandekar, Ratnesh Jain
Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation. Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our review focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for neurodegenerative disorders, as well as the challenges that are posing difficulties in their practical application...
May 10, 2017: Current Gene Therapy
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