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Raffaella Sordella, Nitin H Shirole, Debjani Pal, Edward R Kastenhuber, Serif Senturk, Joseph Boroda, Paola Pisterzi, Madison Miller, Gustavo Munoz, Marko Anderluh, Marc Ladanyi, Scott W Lowe
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD)...
October 19, 2016: ELife
Zhen Yang, Andreas Kappler, Jie Jiang
Humic substances (HS) are redox-active organic compounds with a broad spectrum of molecular sizes and reducing capacities, i.e. number of electrons donated or accepted. However, it is unknown which role the distribution of redox-active functional groups in different molecule sizes plays for HS redox reactions in varying pore sizes micro-environments. We used dialysis experiments to separate bulk humic acids (HA) into low molecular weight fractions (LMWF) and retentate, e.g. the remaining HA in the dialysis bag...
October 19, 2016: Environmental Science & Technology
Sang Jun Lee, Ji Yoon Kang, Wonjoon Choi, Rhokyun Kwak
Nanofluidic resistive pulse sensing (RPS) has been extensively used to measure the size, concentration, and surface charge of nanoparticles in electrically conducting solutions. Although various methods have been explored for improving detection performances, intrinsic problems including the extremely low particle-to-pore volume ratio (<0.01%) and fast nanoparticle translocation (10-1000 µs) still induce difficulties in detection, such as low signal magnitudes and short translocation times. Herein, we present an aqueous two-phase system (ATPS) in a nanofluidic RPS for amplifying translocation signals and decreasing translocation speeds simultaneously...
October 18, 2016: Small
Sher Ali, Tao Xu, Xiaolan Xu
Ca(2+) release-activated Ca(2+) (CRAC) channels play an essential role in the immune system. The pore-forming subunit, Orai1, is an important pharmacological target. Here, we summarize the recent discoveries on the structure-function relationship of Orai1, as well as its interaction with the native channel opener STIM1 and chemical modulator 2-aminoethoxydiphenyl borate (2-APB). We first introduce the critical structural elements of Orai1, which include a Ca(2+) accumulating region (CAR), ion selectivity filter, hydrophobic centre, basic region, extended transmembrane orai1 N-terminal (ETON), transmembrane (TM) regions 2 and 3, P245 bend, (263) SHK(265) hinge linker and L273-L276 hydrophobic patch...
October 18, 2016: Journal of Physiology
Jack R Staunton, Wilfred Vieira, King Leung Fung, Ross Lake, Alexus Devine, Kandice Tanner
One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue's mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs...
September 2016: Cellular and Molecular Bioengineering
Hetal Patel, Hiral Patel, Mukesh Gohel, Sanjay Tiwari
Context: Microcrystalline cellulose (MCC) is the most widely used excipient for the production of pellets but it retards the release of poorly water soluble drugs. Objective: The present investigation reports incorporation of camphor, cross carmellose sodium (CCS) and spray dried lactose (SDL) into MCC pellets to enhance the dissolution rate of telmisartan. Materials and methods: A full factorial design (3(2)) was used in the study. Concentration of camphor and CCS was selected as independent variables whereas percentage porosity and percentage drug release at 60 min were selected as dependent variables...
September 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Peng Zheng, Ting Liu, Shouwu Guo
Superior first-cycle Coulomb efficiency (above 80%) is displayed by filter paper-derived micro-nano structure hard carbon, and it delivers a high reversible capacity of 286 mAh g(-1) after 100 cycles as the anode for Na-ion battery at 20 mA g(-1). These advantageous performance characteristics are attributed to the unique micro-nano structure, which reduced the first irreversible capacity loss by limiting the contact between the electrode and electrolyte, and enhanced the capacity by accelerating electron and Na-ion transfer through inter-connected nano-particles and nano-pores, respectively...
October 18, 2016: Scientific Reports
Liangfa Hu, Morgan O'Neil, Veysel Erturun, Rogelio Benitez, Gwénaëlle Proust, Ibrahim Karaman, Miladin Radovic
The prospect of extending existing metal-ceramic composites to those with the compositions that are far from thermodynamic equilibrium is examined. A current and pressure-assisted, rapid infiltration is proposed to fabricate composites, consisting of reactive metallic and ceramic phases with controlled microstructure and tunable properties. An aluminum (Al) alloy/Ti2AlC composite is selected as an example of the far-from-equilibrium systems to fabricate, because Ti2AlC exists only in a narrow region of the Ti-Al-C phase diagram and readily reacts with Al...
October 18, 2016: Scientific Reports
Wenwen Wang, Yanqin Yang, Zhewen Xiong, Jiamin Kong, Xinlu Fu, Feihai Shen, Zhiying Huang
Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes...
October 14, 2016: Toxicology and Applied Pharmacology
J Mesquita-Guimarães, M A Leite, J C M Souza, B Henriques, F S Silva, D Hotza, A R Boccaccini, M C Fredel
In this work, TiO2 ceramic scaffolds were fabricated by the replica method using polyurethane (PU) sponges. Suspensions with high solid content were used to achieve scaffolds with improved mechanical behavior. TiO2 ceramic suspensions were optimized by rheological studies using different additives. It was found that the composition with 0.5 wt% Darvan enhanced the covering of the sponge struts. PU sponges of 45 to 80 ppi (pore per inch) were well coated without clogging pores. A thermal treatment with varying holding times, temperatures and heating rates was adjusted...
October 17, 2016: Journal of Biomedical Materials Research. Part A
Chun Fang Ma, Qiang Gao, Kai Sheng Xia, Zhi Yuan Huang, Bo Han, Cheng Gang Zhou
The development of bilirubin adsorbents with high adsorption efficiencies towards albumin-bonded bilirubin is still a considerable challenge. In this work, a three-dimensionally porous graphene (3D-pGR) has been fabricated through a simple carbon dioxide (CO2) activation of thermally exfoliated graphite oxide (EGO). Intriguingly, the resultant 3D-pGR material showed hierarchically micro-meso-macroporous structure, high specific surface area of up to 843m(2)g(-1), and large pore volume as high as 2.71cm(3)g(-1)...
October 11, 2016: Colloids and Surfaces. B, Biointerfaces
Yung-Han Shih, Kuen-Yun Wang, Brenda T Singco, Chia-Her Lin, Hsi-Ya Huang
In this study, we first demonstrated the effect of two types of metal-organic framework-polymer (MOF-polymer) monoliths on in-tube solid-phase microextraction (IT-SPME) of sulfonamides. Sulfonamides were successfully adsorbed onto MIL-101(Cr)-polymer but were difficult to elute due to these sulfonamides could interact via Lewis acid-base interaction with the presence of Cr(III) coordinatively unsaturated metal sites (CUS). Moreover, the cage-type topology of MIL-101(Cr) that could produce multiple pathways thus complicates the desorption of the test analytes from the sorbent...
October 17, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Shenli Zhang, Maria Perez-Page, Kelly Guan, Erick Yu, Joseph W Tringe, Ricardo H R Castro, Roland Faller, Pieter Stroeve
Molecular Dynamics (MD) and Monte Carlo (MC) simulations were applied together for the first time to reveal the porous structure transformation mechanisms of mesoporous silica MCM-41 subjected to temperatures up to 2885 K. Silica was experimentally characterized to inform the models and enable prediction of changes in gas adsorption/separation properties. MD simulations suggest that the pore closure process is activated by a collective diffusion of matrix atoms into the porous region, accompanied by bond reformation at the surface...
October 17, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Silvia Panzavolta, Paola Torricelli, Sonia Casolari, Annapaola Parrilli, Sofia Amadori, Milena Fini, Adriana Bigi
The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%)...
October 17, 2016: Macromolecular Bioscience
Bas van Bochove, Gerjon Hannink, Pieter Buma, Dirk W Grijpma
Three-armed poly(trimethylene carbonate) macromers with a relatively high molecular weight of 28.9 kg mol(-1) are prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. A resin suitable for processing by stereolithography is developed using propylene carbonate as a diluent, a photoinitiator, and a dye to control the curing characteristics. The difficulties in building designed structures with digital light processing stereolithography and the ways of optimizing the resin compositions are described in detail...
October 17, 2016: Macromolecular Bioscience
Andrea Buffa, Yigal Erel, Daniel Mandler
A flow-through electrode made of a carbon nanotubes (CNT) film deposited on a polytetrafluoroethylene (PTFE) membrane was assembled and employed for the determination of low concentration of copper as a model system by linear sweep anodic stripping voltammetry (LSASV). CNT films with areal mass ranging from 0.12 to 0.72 mg cm-2 were characterized by measurement of sheet resistance, water permeation flux and capacitance. Moreover, CNT with two different sizes and PTFE membrane with two different pore diameters (0...
October 17, 2016: Analytical Chemistry
Manuel Sánchez, Lorena Suárez, Begoña Cantabrana, Javier Bordallo
Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca(2+) associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca(2+) and noninactivating K(+) currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Carola Stockburger, Davide Miano, Thea Pallas, Kristina Friedland, Walter E Müller
The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity...
2016: Neural Plasticity
James Wilson, Leila Sloman, Zhiren He, Aleksei Aksimentiev
An inexpensive, reliable method for protein sequencing is essential to unraveling the biological mechanisms governing cellular behavior and disease. Current protein sequencing methods suffer from limitations associated with the size of proteins that can be sequenced, the time, and the cost of the sequencing procedures. Here, we report the results of all-atom molecular dynamics simulations that investigated the feasibility of using graphene nanopores for protein sequencing. We focus our study on the biologically significant phenylalanine-glycine repeat peptides (FG-nups)-parts of the nuclear pore transport machinery...
July 19, 2016: Advanced Functional Materials
Ying Zhang, Xiaoyu Guo, Juan Dong
Cell polarization is commonly used for the regulation of stem cell asymmetric division in both animals and plants. Stomatal development in Arabidopsis, a process that produces breathing pores in the epidermis, requires asymmetric cell division to differentiate highly specialized guard cells while maintaining a stem cell population [1, 2]. The BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) protein exhibits a polarized localization pattern in the cell and is required for differential cell fates resulting from asymmetric cell division [3]...
October 5, 2016: Current Biology: CB
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