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Stability engineering

Amiram Sananes, Itay Cohen, Anat Shahar, Alexandra Hockla, Elena De Vita, Aubry K Miller, Evette S Radisky, Niv Papo
Human tissue kallikrein (KLK) proteases are hormone-like signaling molecules with important functions in cancer pathophysiology. KLK-related peptidase 6 (KLK6), specifically, is highly up-regulated in several types of cancer, where its increased activity promotes cancer invasion and metastasis. This characteristic suggests KLK6 as an attractive target for therapeutic interventions. However, inhibitors that specifically target KLK6 have not yet been reported, possibly because KLK6 shares a high sequence homology and structural similarity with other serine proteases and resists inhibition by many polypeptide inhibitors...
June 22, 2018: Journal of Biological Chemistry
Krysta Biniek, Ali Tfayli, Raoul Vyumvuhore, Alessia Quatela, Marie-Florence Galliano, Alexandre Delalleau, Arlette Baillet-Guffroy, Reinhold H Dauskardt, Helene Duplan
An important aspect of the biomechanical behavior of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermost layer of human skin, the SC. Cholesterol plays an important role in stabilizing the SC lipid structure, and altered levels of cholesterol have been linked with SC barrier abnormalities...
June 22, 2018: Experimental Dermatology
Sudip Chakraborty, Amitava Banerjee, Teeraphat Watcharatharapong, Rafael B Araujo, Rajeev Ahuja
A long-standing effort has been devoted for the development of high energy density cathodes both for Li- and Na-ion batteries (LIBs and SIBs). The scientific communities in battery research primarily divide the Li- and Na-ion cathode materials into two categories: layered oxides and polyanionic compounds. Researchers are trying to improve the energy density of such materials through materials screening by mixing the transition metals or changing the concentration of Li or Na in the polyanionic compounds. Due to the fact that there is more stability in the polyanionic frameworks, batteries based on these materials mostly provide a prolonged cycling life as compared to the layered oxide materials...
June 22, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Lie Wu, Jiahong Wang, Jiang Lu, Danni Liu, Na Yang, Hao Huang, Paul K Chu, Xue-Feng Yu
Black phosphorus (BP) possesses unique physical properties and, owing to its intrinsic instability, the proper surface and chemical coordination is the key point in many applications. Herein, a facile and efficient surface lanthanide-coordination strategy based on lanthanide (Ln) sulfonate complexes is designed to passivate and functionalize different BP-based nanostructures including quantum dots, nanosheets, and microflakes. By means of Ln-P coordination, the lone-pair electrons of phosphorus are occupied, thus preventing oxidation of BP, and the LnL3 @BP exhibits excellent stability in both air and water...
June 21, 2018: Small
Ravindra Kumar Gupta, Achalkumar Ammathnadu Sudhakar
Columnar phases formed by the stacking of disc-like molecules with an intimate π-π overlap forms a one-dimensional pathway for the anisotropic charge migration along the columns. Columnar phases have a great potential in organic electronic devices to be utilized as active semiconducting layers in comparison to the organic single crystals or amorphous polymers in terms of processability, ease of handling and high charge carrier mobility. Intelligent molecular engineering of the perylene and its derivatives provided an access to tune the physical properties and self-assembly behavior...
June 22, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
A Schomburg, O S Schilling, C Guenat, M Schirmer, R C Le Bayon, P Brunner
Ecosystem services provided by floodplains are strongly controlled by the structural stability of soils. The development of a stable structure in floodplain soils is affected by a complex and poorly understood interplay of hydrological, physico-chemical and biological processes. This paper aims at analysing relations between fluctuating groundwater levels, soil physico-chemical and biological parameters on soil structure stability in a restored floodplain. Water level fluctuations in the soil are modelled using a numerical surface-water-groundwater flow model and correlated to soil physico-chemical parameters and abundances of plants and earthworms...
October 15, 2018: Science of the Total Environment
Kun Wang, Shuman Wen, Lianghua He, Ang Li, Yan Li, Haiqing Dong, Wei Li, Tianbin Ren, Donglu Shi, Yongyong Li
One of the major challenges in vaccine design has been the over dependence on incorporation of abundant adjuvants, that in fact is in violation of the 'minimalist' principle. In the present study, a compact nanovaccine derived from a near whole antigen (up to 97 wt%) was developed. The nanovaccine structure was stabilized by free cysteines within each antigen (ovalbumin, OVA) which were tempo-spatially exposed and heat-driven to form extensive intermolecular disulfide network. This process enables the engineering of a nanovaccine upon integration of the danger signal (CpG-SH) into the network during the synthetic process...
June 21, 2018: ACS Nano
Petr Popov, Yao Peng, Ling Shen, Raymond C Stevens, Vadim Cherezov, Zhi-Jie Liu, Vsevolod Katritch
Engineering of GPCR constructs with improved thermostability is a key for successful structural and biochemical studies of this transmembrane protein family, targeted by 40% of all therapeutic drugs. Here we introduce a comprehensive computational approach to effective prediction of stabilizing mutations in GPCRs, named CompoMug, which employs sequence-based analysis, structural information, and a derived machine learning predictor. Tested experimentally on the serotonin 5-HT2C receptor target, CompoMug predictions resulted in 10 new stabilizing mutations, with an apparent thermostability gain ~8...
June 21, 2018: ELife
Hanna Maria Gabriella Barriga, Margaret Nancy Holme, Molly M Stevens
Cubosomes are highly stable nanoparticles formed from the lipid cubic phase and stabilized by a polymer based outer corona. Lipid cubic phases consist of a single lipid bilayer which forms a continuous periodic membrane lattice structure with pores formed by two interwoven water channels. Cubosome composition can be tuned to engineer pore sizes or include bioactive lipids, the polymer outer corona can be used for targeting and they are highly stable under physiological conditions. The structure provides a significantly higher membrane surface area for loading of membrane proteins and small drug molecules than liposomes...
June 21, 2018: Angewandte Chemie
Anping Yan, Yunlan Guo, Chao Liu, Zhao Deng, Yi Guo, Xiujian Zhao
Topotactic anion exchange has been developed to tune the composition and band gap energies of cesium lead halide (CsPbX3 ) perovskite nanocrystals (NCs). However, current anion exchange methods either require harsh conditions or take a long time to realize substantial substitution. Here, we present a method to modulate the composition of colloidal CsPbBr3 NCs through ultrasonication-assisted anion exchange with CsX (X = Cl, I) solution. Efficient anion exchange of CsPbBr3 NCs with Cl- or I- is realized with substitution ratio up to 93% and preservation of the pristine shape and structure of CsPbBr3 NCs...
June 20, 2018: Nanoscale Research Letters
Gea Guerriero, Roberto Berni, J Armando Muñoz-Sanchez, Fabio Apone, Eslam M Abdel-Salam, Ahmad A Qahtan, Abdulrahman A Alatar, Claudio Cantini, Giampiero Cai, Jean-Francois Hausman, Khawar Sohail Siddiqui, S M Teresa Hernández-Sotomayor, Mohammad Faisal
Plants are sessile organisms and, in order to defend themselves against exogenous (a)biotic constraints, they synthesize an array of secondary metabolites which have important physiological and ecological effects. Plant secondary metabolites can be classified into four major classes: terpenoids, phenolic compounds, alkaloids and sulphur-containing compounds. These phytochemicals can be antimicrobial, act as attractants/repellents, or as deterrents against herbivores. The synthesis of such a rich variety of phytochemicals is also observed in undifferentiated plant cells under laboratory conditions and can be further induced with elicitors or by feeding precursors...
June 20, 2018: Genes
Titiksha Srivastava, Marine Schott, Roméo Juge, Viola Krizakova, M Belmeguenai, Yves Roussigné, Anne Bernand-Mantel, Laurent Ranno, Stéfania Pizzini, Salim-Mourad Cherif, Andrei Stashkevich, Stéphane Auffret, Olivier Boulle, Gilles Gaudin, Mairbek Chshiev, Claire Baraduc, Hélène Béa
Electric field control of interfacial magnetism promises low power consuming and versatile spintronic devices. More specifically, in ultra thin heavy metal/ferromagnet/insulator heterostructures, voltage gating has been shown to locally and dynamically tune properties like perpendicular magnetic anisotropy and saturation magnetization. However its effect on the nowadays widely explored antisymmetric exchange property called interfacial Dzyaloshinskii-Moriya Interaction (DMI) has not been addressed yet. This DMI plays a fundamental role in stabilizing magnetic textures known as skyrmions envisaged for memory and logic based spintronic devices...
June 20, 2018: Nano Letters
J L Slon Campos, M Poggianella, O R Burrone
Dengue virus (DENV) is one the most important viral pathogens worldwide. Currently there is an imperative need for a reliable vaccine capable of inducing durable protection against all four serotypes. We have previously reported strongly neutralizing and highly specific antibody responses from all four serotypes to a DNA vaccine based on an engineered version of DENV E protein's domain III (DIII). Here, we show that monovalent and tetravalent immunizations with the DIII-based DNA vaccines are also capable of inducing highly stable antibody responses that remain strongly neutralizing over long periods of time...
June 20, 2018: Journal of General Virology
Urmimala Dey, Swastika Chatterjee, A Taraphder
It has been realized lately that disorder, primarily in the form of oxygen vacancies, cation stoichiometry, atomic inter-diffusion and antisite defects, has a major effect on the electronic and transport properties of a 2D electron liquid at oxide hetero-interfaces - the first and the last being the two key players. In order to delineate the roles of these two key factors, we have investigated the effect of oxygen vacancies on the antisite disorder at a large number of interfaces separating two La-based transition metal oxides, using density functional theory...
June 20, 2018: Physical Chemistry Chemical Physics: PCCP
Jasmin Hum, Aldo R Boccaccini
Highly porous 45S5 bioactive glass-based scaffolds were fabricated by the foam replica technique and coated with collagen by a novel method. After an initial cleaning step of the bioactive glass surface to expose reactive ⁻OH groups, samples were surface functionalized by (3-aminopropyl)triethoxysilane (APTS). Functionalized scaffolds were immersed in a collagen solution, left for gelling at 37 °C, and dried at room temperature. The collagen coating was further stabilized by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N -hydroxysuccinimide (NHS)...
June 19, 2018: International Journal of Molecular Sciences
Anna-Carin C Carlsson, Matthew R Scholfield, Rhianon Kay Rowe, Melissa Coates Ford, Austin T Alexander, Ryan A Mehl, Pui Shing Ho
The construction of more stable proteins is important in biomolecular engineering, particularly in the design of biologics based therapeutics. We show here that replacing the tyrosine at position 18 (Y18) of T4 lysozyme with the unnatural amino acid meta-chlorotyrosine (mCl Y) increases both the thermal stability (raising the melting temperature by ~1°C and melting enthalpy by 3 kcal/mol) and enzymatic activity at elevated temperatures (15% higher than the parent enzyme at 40°C) of this classic enzyme. The chlorine of mCl Y forms a halogen bond (XB) to the carbonyl oxygen of the peptide bond at glycine 28 (G28) in a tight loop near the active site...
June 19, 2018: Biochemistry
Chiu-Mei Hsueh, Hung-Ming Lin, Te-Yu Tseng, Yao-De Huang, Hsuan-Shu Lee, Chen-Yuan Dong
Second order susceptibility (SOS) microscopy is used to image and characterize chondrogenesis in cultured human mesesnchymal stem cells (hMSCs). SOS analysis shows that the second order susceptibility tensor ratios can be used to characterize type I and II collagens in living tissues and that both collagen types are produce at the onset of chondrogenesis. Time-lapse analysis shows a modulation of extracellular matrix results in an higher rate in increase of type II collagen, as compared to type I collagen. With time, type II collagen content stabilizes at the composition of 70% of total collagen content...
June 19, 2018: Journal of Biophotonics
Weihua Chen, Lupeng Zhang, Chuntai Liu, Xiangming Feng, Jianmin Zhang, Linquan Guan, Li-Wei Mi, Shizhong Cui
Na-ion battery is one of the best technologies for large-scale applications depending on almost infinite and widespread sodium resources. However, the state-of-the-art separators cannot meet the engineering needs of large-scale sodium-ion batteries to match the intensively investigated electrode materials. Here, a kind of flexible modified cellulose acetate separator (MCA) for sodium-ion batteries was synthesized via electrospinning process and subsequent optimizing the interface chemical groups by changing acetyl to hydroxyl partly...
June 19, 2018: ACS Applied Materials & Interfaces
Shefah Qazi, Christopher J Schlicksup, Jonathan Rittichier, Michael S VanNieuwenhze, Adam Zlotnick
The Hepatitis B Virus (HBV) core protein homodimers self-assemble to form an icosahedral capsid that packages the viral genome. Disassembly occurs in the nuclear basket to release the mature genome to the nucleus. Small molecules have been developed that bind to a pocket at the inter-dimer interface to accelerate assembly and strengthen interactions between subunits; these are under development as antiviral agents. Here, we explore the role of the dimer-dimer interface by mutating sites in the pocket to cysteine and examining the effect of covalently linking small molecules to them...
June 19, 2018: ACS Chemical Biology
Linxing Zhang, Bo Li, Jifeng Yuan, Mengru Wang, Ting Shen, Fei Huang, Wen Wen, Guozhong Cao, Jianjun Tian
Inorganic halide perovskites exhibit significant photovoltaic performance due to their structural stability and high open-circuit voltage ( Voc ). Herein, a general strategy of solution engineering has been implemented to enable a wide solution-processing window for high Voc (∼1.3 V) and power conversion efficiency (PCE, ∼12.5%). We introduce a nontoxic solvent of dimethyl sulfoxide (DMSO) and an assisted heating process in the fabrication of CsPbI2 Br (CPI2) to control the improved crystallization. A wide solution-processing window including a wide range of solvent components and solute concentrations has been realized...
June 20, 2018: Journal of Physical Chemistry Letters
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