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Lyndon da Cruz, Kate Fynes, Odysseas Georgiadis, Julie Kerby, Yvonne H Luo, Ahmad Ahmado, Amanda Vernon, Julie T Daniels, Britta Nommiste, Shazeen M Hasan, Sakina B Gooljar, Amanda-Jayne F Carr, Anthony Vugler, Conor M Ramsden, Magda Bictash, Mike Fenster, Juliette Steer, Tricia Harbinson, Anna Wilbrey, Adnan Tufail, Gang Feng, Mark Whitlock, Anthony G Robson, Graham E Holder, Mandeep S Sagoo, Peter T Loudon, Paul Whiting, Peter J Coffey
Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more...
March 19, 2018: Nature Biotechnology
Thomas H Segall-Shapiro, Eduardo D Sontag, Christopher A Voigt
The internal environment of growing cells is variable and dynamic, making it difficult to introduce reliable parts, such as promoters, for genetic engineering. Here, we applied control-theoretic ideas to design promoters that maintained constant levels of expression at any copy number. Theory predicts that independence to copy number can be achieved by using an incoherent feedforward loop (iFFL) if the negative regulation is perfectly non-cooperative. We engineered iFFLs into Escherichia coli promoters using transcription-activator-like effectors (TALEs)...
March 19, 2018: Nature Biotechnology
Mark J Bailey, Felix Broecker, Paul E Leon, Gene S Tan
Antibodies play a crucial role in coupling the innate and adaptive immune responses against viral pathogens through their antigen binding domains and Fc-regions. Here, we describe how to measure the activation of Fc effector functions by monoclonal antibodies targeting the influenza virus hemagglutinin with the use of a genetically engineered Jurkat cell line expressing an activating type 1 Fc-FcγR. Using this method, the contribution of specific Fc-FcγR interactions conferred by immunoglobulins can be determined using an in vitro assay...
February 23, 2018: Journal of Visualized Experiments: JoVE
Xiaonan Zhang, Quentin Gaudry
Here, a new technique termed Tetrotoxin (TTX) Engineered Resistance for Probing Synapses (TERPS) is applied to test for monosynaptic connections between target neurons. The method relies on co-expression of a transgenic activator with the tetrodotoxin-resistant sodium channel, NaChBac, in a specific presynaptic neuron. Connections with putative post-synaptic partners are determined by whole-cell recordings in the presence of TTX, which blocks electrical activity in neurons that do not express NaChBac. This approach can be modified to work with any activator or calcium imaging as a reporter of connections...
February 14, 2018: Journal of Visualized Experiments: JoVE
Kensuke Ihara, Koji Sugiyama, Kentaro Takahashi, Masahiro Yamazoe, Tetsuo Sasano, Tetsushi Furukawa
Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts...
February 22, 2018: Journal of Visualized Experiments: JoVE
Mads Gilbert
BACKGROUND: The atrocities in Syria have been covered in the four general medical weekly journals in the USA and the UK. Medical journal articles addressing political determinants of public health have rightly described and criticised the international community's failure to enforce humanitarian law while urging global bodies of power to ensure protection of civilians and civilian infrastructure and medical services. Discussions of the political influences on health of people in the occupied Palestinian territory (West Bank and Gaza Strip) seem to be considered politically out-of-bounds by some medical journals...
February 21, 2018: Lancet
Xiuxiu Wang, Ru Cheng, Liang Cheng, Zhiyuan Zhong
PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs)...
March 19, 2018: Biomacromolecules
Adriely Goes, Gregor Fuhrmann
Biogenic and biomimetic therapeutics are a relatively new class of systems that are of physiological origin and/or take advantage of natural pathways, or aim at mimicking these to improve selective interaction with target tissue. The number of biogenic and bioengineered avenues for drug therapy and diagnostics has multiplied over the past years for many applications, indicating the high expectations associated with this biological route. Nevertheless, the use of "bio"-related approaches for treating or diagnosing infectious diseases is still rare...
March 19, 2018: ACS Infectious Diseases
José Luis Suarez-Franco, Febe Carolina Vázquez-Vázquez, Amaury Pozos-Guillen, Juan José Montesinos, Octavio Alvarez-Fregoso, Marco Antonio Alvarez-Perez
This study evaluated the influence in the biocompatibility of human periodontal ligament (hPDL) mesenchymal stromal cell onto poly lactic-acid (PLA) films and PLA fiber membrane. Fiber scaffold was prepared via air jet spinning (AJS) from PLA solutions (6, 7, and 10%) and analyzed using SEM, AFM and FTIR. Biocompatibility was evaluated by adhesion, proliferation and cell-material interaction. PLA film exhibited a smooth and homogenously surface topography in comparison with random orientation of PLA fiber with roughness structure where diameter size depends on PLA solution...
March 17, 2018: Dental Materials Journal
Christian Baeumer, Martin Janson, Beate Timmermann, Jörg Wulff
AIM: To assess if apertures shall be mounted upstream or downstream of a range shifting block if these field-shaping devices are combined with the pencil-beam scanning delivery technique (PBS). The lateral dose fall-off served as a benchmark parameter. Both options realizing PBS-with-apertures were compared to the uniform scanning mode. We also evaluated the difference regarding the out-of-field dose caused by interactions of protons in beam-shaping devices.
 Methods: The potential benefit of the downstream configuration over the upstream configuration was estimated analytically...
March 19, 2018: Physics in Medicine and Biology
Celeste H Claudio, Zoelle B Dizon, Tessie W October
BACKGROUND: Accessible information about palliative care available to the public on the Internet is growing. We do not know whether this information is consistent with the current accepted definition of palliative care. AIM: To identify resources on the Internet and social media regarding palliative care and evaluate the information conveyed. DESIGN: A cross-sectional study of "palliative care" search results. SETTING: Top 10 Google websites, top 10 most viewed YouTube videos, and social media platforms, Facebook and Twitter, were searched...
January 1, 2018: American Journal of Hospice & Palliative Care
Jaime Agudo-Canalejo, Pierre Illien, Ramin Golestanian
Chemotaxis of enzymes in response to gradients in the concentration of their substrate has been widely reported in recent experiments, but a basic understanding of the process is still lacking. Here, we develop a microscopic theory for chemotaxis, valid for enzymes and other small molecules. Our theory includes both non-specific interactions between enzyme and substrate, as well as complex formation through specific binding between the enzyme and the substrate. We find that two distinct mechanisms contribute to enzyme chemotaxis: a diffusiophoretic mechanism due to the non-specific interactions, and a new type of mechanism due to binding-induced changes in the diffusion coefficient of the enzyme...
March 19, 2018: Nano Letters
Huanyu Jin, Chunxian Guo, Xin Liu, Jinlong Liu, Anthony Vasileff, Yan Jiao, Yao Zheng, Shi-Zhang Qiao
Over the past few decades, the design and development of advanced electrocatalysts for efficient energy conversion technologies have been subjects of extensive study. With the discovery of graphene, two-dimensional (2D) nanomaterials have emerged as some of the most promising candidates for heterogeneous electrocatalysts due to their unique physical, chemical, and electronic properties. Here, we review 2D-nanomaterial-based electrocatalysts for selected electrocatalytic processes. We first discuss the unique advances in 2D electrocatalysts based on different compositions and functions followed by specific design principles...
March 19, 2018: Chemical Reviews
Meng-Die Qi, Jian Wang, Xiao-Jing Ma, Quan Zhang, Fang-Fang Wang, Ying Kang, Hui-Xin Lin, Yong Liu
Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculata,with a variety of pharmacological activity,widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this study,the coding sequence of A. paniculata CPR was screened and cloned by homologous alignment,named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Cheng-En Dai, Hai-Long Li, Xiao-Ping He, Fen-Fen Zheng, Hua-Liu Zhu, Liang-Feng Liu, Wei Du
The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Mitchell S Weisenberger, Tara L Deans
Synthetic biologists use engineering principles to design and construct genetic circuits for programming cells with novel functions. A bottom-up approach is commonly used to design and construct genetic circuits by piecing together functional modules that are capable of reprogramming cells with novel behavior. While genetic circuits control cell operations through the tight regulation of gene expression, a diverse array of environmental factors within the extracellular space also has a significant impact on cell behavior...
March 19, 2018: Journal of Industrial Microbiology & Biotechnology
Qinqin Zhao, Huixin Xie, Yao Peng, Xinran Wang, Linquan Bai
The α-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp. and used as a potent drug in the treatment of type-2 diabetes. In order to improve the yield of acarbose, an efficient genetic manipulation system for Actinoplanes sp. was established. The conjugation system between E. coli carrying ØC31-derived integrative plasmids and the mycelia of Actinoplanes sp. SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture (mycelia and E. coli ), quantity of recipient cells, donor-to-recipient ratio and the concentration of MgCl2 , which resulted in a high conjugation efficiency of 29...
December 2017: Synthetic and Systems Biotechnology
Erqing Jin, Lynn Wong, Yun Jiao, Jake Engel, Benjamin Holdridge, Peng Xu
Engineering cell factories for producing biofuels and pharmaceuticals has spurred great interests to develop rapid and efficient synthetic biology tools customized for modular pathway engineering. Along the way, combinatorial gene expression control through modification of regulatory element offered tremendous opportunity for fine-tuning gene expression and generating digital-like genetic circuits. In this report, we present an efficient evolutionary approach to build a range of regulatory control elements...
December 2017: Synthetic and Systems Biotechnology
Kanchana Rueksomtawin Kildegaard, Belén Adiego-Pérez, David Doménech Belda, Jaspreet Kaur Khangura, Carina Holkenbrink, Irina Borodina
Astaxanthin is a red-colored carotenoid, used as food and feed additive. Astaxanthin is mainly produced by chemical synthesis, however, the process is expensive and synthetic astaxanthin is not approved for human consumption. In this study, we engineered the oleaginous yeast Yarrowia lipolytica for de novo production of astaxanthin by fermentation. First, we screened 12 different Y. lipolytica isolates for β-carotene production by introducing two genes for β-carotene biosynthesis: bi-functional phytoene synthase/lycopene cyclase ( crtYB ) and phytoene desaturase ( crtI ) from the red yeast Xanthophyllomyces dendrorhous ...
December 2017: Synthetic and Systems Biotechnology
Jian Zha, Mattheos A G Koffas
Microbial production of plant-derived natural products by engineered microorganisms has achieved great success thanks to large extend to metabolic engineering and synthetic biology. Anthocyanins, the water-soluble colored pigments found in terrestrial plants that are responsible for the red, blue and purple coloration of many flowers and fruits, are extensively used in food and cosmetics industry; however, their current supply heavily relies on complex extraction from plant-based materials. A promising alternative is their sustainable production in metabolically engineered microbes...
December 2017: Synthetic and Systems Biotechnology
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