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https://www.readbyqxmd.com/read/28318221/crystal-structure-of-a-homogeneous-igg-fc-glycoform-with-the-n-glycan-designed-to-maximize-the-antibody-dependent-cellular-cytotoxicity
#1
Chia-Lin Chen, Jen-Chi Hsu, Chin-Wei Lin, Chia-Hung Wang, Ming-Hung Tsai, Chung-Yi Wu, Chi-Huey Wong, Che Ma
N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain, and solved its crystal structure...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28315083/achieving-the-promise-of-therapeutic-extracellular-vesicles-the-devil-is-in-details-of-therapeutic-loading
#2
REVIEW
Dhruvitkumar S Sutaria, Mohamed Badawi, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells...
March 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28306753/non-monotonic-dependence-of-pickering-emulsion-gel-rheology-on-particle-volume-fraction
#3
M Kaganyuk, A Mohraz
The microstructure of Pickering emulsion gels features a tenuous network of faceted droplets, bridged together by shared monolayers of particles. In this investigation, we use standard oscillatory rheometry in conjunction with confocal microscopy to gain a more comprehensive understanding of the role particle bridged interfaces have on the rheology of Pickering emulsion gels. The zero-shear elastic modulus of Pickering emulsion gels shows a non-monotonic dependence on particle loading, with three separate regimes of power-law and linear gel strengthening, and subsequent gel weakening...
March 17, 2017: Soft Matter
https://www.readbyqxmd.com/read/28306190/natural-polymeric-hydrogel-evaluation-for-skeletal-muscle-tissue-engineering
#4
Beth E Pollot, Christopher R Rathbone, Joseph C Wenke, Teja Guda
Although skeletal muscle has a remarkable ability to repair/regenerate after most types of injuries, there is limited regeneration after volumetric muscle loss (VML). A number of scaffold materials have been used in the development of grafts to treat VML, however, there is still a need to better understand the most appropriate material with regards to its ability to maintain mechanical integrity while also supporting myogenesis. Five commonly used natural polymeric materials (Collagen I, Agarose, Alginate, Fibrin, and Collagen Chitosan) used in skeletal muscle tissue engineering grafts were evaluated for their mechanical properties and myogenic capacity...
March 17, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28303026/strategies-and-challenges-for-the-next-generation-of-antibody-drug-conjugates
#5
REVIEW
Alain Beck, Liliane Goetsch, Charles Dumontet, Nathalie Corvaïa
Antibody-drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60 further ADC candidates. The limited success of first-generation ADCs (developed in the early 2000s) informed strategies to bring second-generation ADCs to the market, which have higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28301732/nanoengineering-heterogeneous-catalysts-by-atomic-layer-deposition
#6
Joseph A Singh, Nuoya Yang, Stacey F Bent
A new generation of catalysts is needed to meet society's energy and resource requirements. Current catalyst synthesis does not fully achieve optimum control of composition, size, and structure. Atomic layer deposition (ALD) is an emerging technique that allows synthesizing of highly controlled catalysts in the forms of films, nanoparticles, and single sites. The addition of ALD coatings can also be used to introduce promoters and improve the stability of traditional catalysts. Evolving research shows promise for applying ALD to understand catalytically active sites and create next-generation catalysts using advanced 3D nanostructures...
February 27, 2017: Annual Review of Chemical and Biomolecular Engineering
https://www.readbyqxmd.com/read/28300586/pectins-functionalized-biomaterials-a-new-viable-approach-for-biomedical-applications-a-review
#7
Aqdas Noreen, Zill-I-Huma Nazli, Javeria Akram, Ijaz Rasul, Asim Mansha, Nazia Yaqoob, Rehana Iqbal, Shazia Tabasum, Mohammad Zuber, Khalid Mahmood Zia
Pectins are natural complex heteropolysaccharides, composed of (1, 4)-linked α-D-galacturonic acid residues and variety of neutral sugars such as rhamnose, galactose, arabinose. It is second most abundant component of the cell wall of all land plants. It has wide applications in various fields due to its use as gelling, emulsifying or stabilizing agent and as well as its non-toxic, biocompatible and biodegradable nature. Considering these versatile properties this review sheds a light on the synthesis, modification, characterization and applications of pectin based polymers...
March 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28300077/translational-reprogramming-in-tumour-cells-can-generate-oncoselectivity-in-viral-therapies
#8
Eneko Villanueva, Pilar Navarro, Maria Rovira-Rigau, Annarita Sibilio, Raúl Méndez, Cristina Fillat
Systemic treatment of cancer requires tumour-selective therapies that eliminate cancer cells yet preserve healthy tissues from undesired damage. Tumoral transformation is associated with profound effects in translational reprogramming of gene expression, such that tumour-specific translational regulation presents an attractive possibility for generating oncoselective therapies. We recently discovered that mRNA translational control by cytoplasmic polyadenylation element-binding proteins (CPEBs) is reactivated in cancer...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#9
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
March 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28298296/fabrication-of-synthetic-mesenchymal-stem-cells-for-the-treatment-of-acute-myocardial-infarction-in-mice
#10
Lan Luo, Junnan Tang, Kodai Nishi, Chen Yan, Phuong-Uyen Dinh, Jhon Cores, Takashi Kudo, Jinying Zhang, Tao-Sheng Li, Ke Cheng
Rationale: Stem cell therapy faces a number of challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into Poly(lactic-co-glycolic acid) PLGA microparticles and then coated them with MSC membranes...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28298220/enzymatic-improvement-of-mitochondrial-thiol-oxidase-erv1-for-oxidized-glutathione-fermentation-by-saccharomyces-cerevisiae
#11
Jyumpei Kobayashi, Daisuke Sasaki, Kiyotaka Y Hara, Tomohisa Hasunuma, Akihiko Kondo
BACKGROUND: Oxidized glutathione (GSSG) is the preferred form for industrial mass production of glutathione due to its high stability compared with reduced glutathione (GSH). In our previous study, over-expression of the mitochondrial thiol oxidase ERV1 gene was the most effective for high GSSG production in Saccharomyces cerevisiae cells among three types of different thiol oxidase genes. RESULTS: We improved Erv1 enzyme activity for oxidation of GSH and revealed that S32 and N34 residues are critical for the oxidation...
March 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28297638/buckling-instabilities-and-complex-trajectories-in-a-simple-model-of-uniflagellar-bacteria
#12
Frank T M Nguyen, Michael D Graham
Observations of uniflagellar bacteria show that buckling instabilities of the hook protein connecting the cell body and flagellum play a role in locomotion. To understand this phenomenon, we develop models at varying levels of description with a particular focus on the parameter dependence of the buckling instability. A key dimensionless group called the flexibility number measures the hook flexibility relative to the thrust exerted by the flagellum; this parameter and the geometric parameters of the cell determine the stability of straight swimming...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28296197/engineering-bimetallic-ag-cu-nanoalloys-for-highly-efficient-oxygen-reduction-catalysts-a-guideline-for-designing-ag-based-electrocatalysts-with-activity-comparable-to-pt-c-20
#13
Xiaoqiang Wu, Fuyi Chen, Nan Zhang, Adnan Qaseem, Roy L Johnston
Development of highly active and stable Pt-free oxygen reduction reaction catalysts from earth-abundant elements remains a grand challenge for highly demanded metal-air batteries. Ag-based alloys have many advantages over platinum group catalysts due to their low cost, high stability, and acceptable oxygen reduction reaction (ORR) performance in alkaline solutions. Nevertheless, compared to commercial Pt/C-20%, their catalytic activity still cannot meet the demand of commercialization. In this study, a kind of catalysts screening strategy on Agx Cu100-x nanoalloys is reported, containing the surface modification method, studies of activity enhancement mechanism, and applied research on zinc-air batteries...
March 15, 2017: Small
https://www.readbyqxmd.com/read/28295800/self-rolled-porous-hollow-tubes-made-up-of-biodegradable-polymers
#14
Ling Peng, Jian Zhu, Seema Agarwal
A tubular highly porous scaffold of polylactide (PLA) and poly-ε-caprolactone (PCL) is fabricated by self-rolling of a 2D fibrous bilayer of PLA and PCL in water without use of any classical thermo-/pH-responsive polymers. The self-rolling and diameter of the tube are dependent upon the bilayer thickness and temperature. A 75 µm thick 2D bilayer (PLA = 25 µm; PCL = 50 µm) rolls to a hollow tube of diameter around 0.41 mm with multilayered wall at 40 °C within 5 min. The tubes keep their form and size in water at all temperatures once they are formed...
March 15, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28294042/green-synthesized-nanomaterials-as-theranostic-platforms-for-cancer-treatment-principles-challenges-and-the-road-ahead
#15
Pala Rajasekharreddy, Chao Huang, Siddhardha Busi, Jobina Rajkumari, Ming-Hong Tai, Gang Liu
With the emergence of nanotechnology, new methods have been developed for engineering various nanoparticles for biomedical applications. Nanotheranostics is a burgeoning research field with tremendous prospects for the improvement of diagnosis and treatment of various cancers. However, the development of biocompatible and efficient drug/gene delivery theranostic systems still remains a challenge. Green synthetic approach of nanoparticles with low capital and operating expenses, reduced environmental pollution and better biocompatibility and stability is a latest and novel field, which is advantageous over chemical or physical nanoparticle synthesis methods...
March 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28293891/development-of-a-synthetic-switch-to-control-protein-stability-in-eukaryotic-cells-with-light
#16
Christof Taxis
In eukaryotic cells, virtually all regulatory processes are influenced by proteolysis. Thus, synthetic control of protein stability is a powerful approach to influence cellular behavior. To achieve this, selected target proteins are modified with a conditional degradation sequence (degron) that responds to a distinct signal. For development of a synthetic degron, an appropriate sensor domain is fused with a degron such that activity of the degron is under control of the sensor. This chapter describes the development of a light-activated, synthetic degron in the model organism Saccharomyces cerevisiae...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28293881/ancestral-protein-reconstruction-and-circular-permutation-for-improving-the-stability-and-dynamic-range-of-fret-sensors
#17
Ben E Clifton, Jason H Whitfield, Inmaculada Sanchez-Romero, Michel K Herde, Christian Henneberger, Harald Janovjak, Colin J Jackson
Small molecule biosensors based on Förster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28293878/construction-of-allosteric-protein-switches-by-alternate-frame-folding-and-intermolecular-fragment-exchange
#18
Jeung-Hoi Ha, Stewart N Loh
Alternate frame folding (AFF) and protein/fragment exchange (FREX) are related technologies for engineering allosteric conformational changes into proteins that have no pre-existing allosteric properties. One of their chief purposes is to turn an ordinary protein into a biomolecular switch capable of transforming an input event into an optical or functional readout. Here, we present a guide for converting an arbitrary binding protein into a fluorescent biosensor with Förster resonance energy transfer output...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28293752/acoustic-emission-signatures-during-failure-of-vertebra-and-long-bone
#19
Brian D Goodwin, Frank A Pintar, Narayan Yoganandan
Clinical classification of an injury has traditionally involved medical imaging, patient history, and physical examination. The pathogenesis or process of injury has been viewed as a crucial component to estimating fracture stability and direct treatment. However, injury classification systems generally exclude pathogenesis and injury mechanisms because these components are often difficult to elucidate. Furthermore, the development of bone damage relative to the mechanical response is difficult to quantify, which limits the ability to define injury and develop injury criteria...
March 14, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28292179/cross-linking-approaches-to-tuning-the-mechanical-properties-of-peptide-%C3%AF-electron-hydrogels
#20
Wathsala Liyanage, Herdeline Ann M Ardoña, Hai-Quan Mao, John D Tovar
Self-assembling peptides are extensively exploited as bioactive materials in applications such as regenerative medicine and drug delivery despite the fact that their relatively weak noncovalent interactions often render them susceptible to mechanical destruction and solvent erosion. Herein, we describe how covalent cross-linking enhances the mechanical stability of self-assembling π-conjugated peptide hydrogels. We designed short peptide-chromophore-peptide sequences displaying different reactive functional groups that can form cross-links with appropriately modified bifunctional polyethylene glycol (PEG)-based small guest molecules...
March 15, 2017: Bioconjugate Chemistry
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