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Krishnashish Bose, Christopher J Lech, Brahim Heddi, Anh Tuân Phan
We investigate the self-assembly of short pieces of the Tetrahymena telomeric DNA sequence d[G4 T2 G4 ] in physiologically relevant aqueous solution using atomic force microscopy (AFM). Wire-like structures (G-wires) of 3.0 nm height with well-defined surface periodic features were observed. Analysis of high-resolution AFM images allowed their classification based on the periodicity of these features. A major species is identified with periodic features of 4.3 nm displaying left-handed ridges or zigzag features on the molecular surface...
May 17, 2018: Nature Communications
Benjamin S Miller, Claudio Parolo, Valerian Turbé, Candice E Keane, Eleanor R Gray, Rachel McKendry
We report a novel ultralow-cost biochemical analysis platform to quantify protein dissociation binding constants and kinetics using paper microfluidics. Our approach marries video imaging with one of humankind's oldest materials - paper, requiring no large, expensive laboratory equipment, complex microfluidics or external power. Temporal measurements of nanoparticle-antibody conjugates binding on paper is found to follow the Langmuir Adsorption Model. This is exploited to measure a series of antibody-antigen dissociation constants on paper, showing excellent agreement with a gold-standard benchtop interferometer...
May 17, 2018: Chemistry: a European Journal
O Morgan Hall, Cody J Peer, William D Figg
Surgical intervention is a common treatment modality for localized cancer. Post-operative analysis involves evaluation of surgical margins to assess whether all malignant tissue has been resected because positive surgical margins lead to a greater likelihood of recurrence. Secondary treatments are utilized to minimize the negative effects of positive surgical margins. Recently, in Science Translational Medicine, Zhang et al describe a new mass spectroscopic technique that could potentially decrease the likelihood of positive surgical margins...
May 17, 2018: Cancer Biology & Therapy
Gang Wan, Brandon D Fields, George Spracklin, Aditi Shukla, Carolyn M Phillips, Scott Kennedy
Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule...
May 16, 2018: Nature
Giovanni N Roviello
This article deals with the synthesis in solid phase and characterization of a nucleoamino amide, based on a phenylalaninamide moiety which was N-conjugated to a thymine nucleobase. In analogy to the natural nucleobase-amino acid conjugates, endowed with a wide range of biological properties, the nucleoamino amide interacts with single-stranded nucleic acids as verified in DNA- and RNA-binding assays conducted by CD and UV spectroscopies. These technologies were used to show also that this conjugate binds serum proteins altering significantly their secondary structure, as evidenced by CD and UV using BSA as a model...
May 15, 2018: Amino Acids
Guido Bolognesi, Mark S Friddin, Ali Salehi-Reyhani, Nathan E Barlow, Nicholas J Brooks, Oscar Ces, Yuval Elani
Constructing higher-order vesicle assemblies has discipline-spanning potential from responsive soft-matter materials to artificial cell networks in synthetic biology. This potential is ultimately derived from the ability to compartmentalise and order chemical species in space. To unlock such applications, spatial organisation of vesicles in relation to one another must be controlled, and techniques to deliver cargo to compartments developed. Herein, we use optical tweezers to assemble, reconfigure and dismantle networks of cell-sized vesicles that, in different experimental scenarios, we engineer to exhibit several interesting properties...
May 14, 2018: Nature Communications
Priscillia Lagoutte, Charlotte Mignon, Gustavo Stadthagen, Supanee Potisopon, Stéphanie Donnat, Jan Mast, Adrien Lugari, Bettina Werle
In the past decades protein nanoparticles have successfully been used for vaccine applications. Their particulate nature and dense repetitive subunit organization makes them perfect carriers for antigen surface display and confers high immunogenicity. Nanoparticles have emerged as excellent candidates for vectorization of biological and immunostimulating molecules. Nanoparticles and biomolecular nanostructures such as ferritins or virus like particles have been used as diagnostic and therapeutic delivery systems, in vaccine development, as nanoreactors, etc...
May 11, 2018: Vaccine
Maria Romano, Giuliana Fusco, Hassanul G Choudhury, Shahid Mehmood, Carol V Robinson, Séverine Zirah, Julian D Hegemann, Ewen Lescop, Mohamed A Marahiel, Sylvie Rebuffat, Alfonso De Simone, Konstantinos Beis
Bacteria under stress produce ribosomally synthesized and posttranslationally modified peptides (RiPPs) to target closely related species, such as the lasso peptide microcin J25 (MccJ25). These peptides are also toxic to the producing organisms that utilize dedicated ABC transporters to achieve self-immunity. MccJ25 is exported by the Escherichia coli ABC transporter McjD through a complex mechanism of recognition that has remained elusive. Here, we used biomolecular NMR to study this interaction and identified a region of the toxic peptide that is crucial to its recognition by the ABC transporter...
May 14, 2018: ACS Chemical Biology
Derin Sevenler, George G Daaboul, Fulya Ekiz Kanik, Nese Lortlar Ünlü, M Selim Ünlu
DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and limited dynamic range of traditional fluorescence microarrays compared to other detection techniques have been the technology's Achilles' Heel, and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ('digital') regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages...
May 14, 2018: ACS Nano
M Bonacina, D Albano, N Steimberg, G Bosio, L Camoni, F Bertagna, R Giubbini, G Mazzoleni
PURPOSE: After radiopharmaceutical injection, a heightened 123 I-MIBG concentration is frequently observed in the left hepatic lobe compared to the right one, but the reason of this finding remains unknown. Our aim was to retrospectively analyze the different 123 I-MIBG uptake pattern between the two hepatic lobes and correlate our results with some epidemiological/clinical features. MATERIAL AND METHODS: Ninety-four 123 I-MIBG scintigraphies from 71 patients were selected...
May 10, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
Tairan Yuwen, Guillaume Bouvignies, Lewis E Kay
Chemical Exchange Saturation Transfer (CEST) has emerged as a powerful tool for studies of biomolecular conformational exchange involving the interconversion between a major, visible conformer and one or more minor, invisible states. Applications typically entail recording a large number of 2D datasets, each of which differs in the position of a weak radio frequency field, so as to generate a CEST profile for each nucleus from which the chemical shifts of spins in the invisible state(s) are obtained. Here we compare a number of band-selective CEST schemes for speeding up the process using either DANTE or cosine-modulated excitation approaches...
April 26, 2018: Journal of Magnetic Resonance
Baker Syed, M N Nagendra Prasad, K Mohan Kumar, S Satish
The present study emphasizes the need for novel antimicrobial agents to combat the global drug resistant crisis. The development of novel nanomaterials is reported to be of the alternative tool to combat drug resistant pathogens. In present investigation, bioconjugated nano-complex was developed from secondary metabolite secreted from endosymbiont. The endosymbiont capable of secreting antimicrobial metabolite was subjected to fermentation and the culture supernatant was assessed for purification of antimicrobial metabolite via bio-assay guided fraction techniques such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and column chromatography...
May 9, 2018: Science of the Total Environment
João M C Teixeira, Simon P Skinner, Miguel Arbesú, Alexander L Breeze, Miquel Pons
We present Farseer-NMR ( ), a software package to treat, evaluate and combine NMR spectroscopic data from sets of protein-derived peaklists covering a range of experimental conditions. The combined advances in NMR and molecular biology enable the study of complex biomolecular systems such as flexible proteins or large multibody complexes, which display a strong and functionally relevant response to their environmental conditions, e.g. the presence of ligands, site-directed mutations, post translational modifications, molecular crowders or the chemical composition of the solution...
May 11, 2018: Journal of Biomolecular NMR
Michele Lauriola, Antonio Mangiacotti, Grazia D'Onofrio, Leandro Cascavilla, Francesco Paris, Giulia Paroni, Davide Seripa, Antonio Greco, Daniele Sancarlo
Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS)...
May 3, 2018: Nutrients
Jeffrey B Woodruff
Cells compartmentalize biochemical reactions using organelles, which can be membrane-enclosed or built entirely of proteins and ribonucleic acids. Recent studies indicate that many organelles which lack membranes have liquid-like properties, including the ability to flow, fuse, and undergo rapid internal rearrangement. The assembly of these "biomolecular condensates" has been described as liquid-liquid phase separation, whereby their constituent components demix from the cytoplasm, similar to water separating from oil...
May 8, 2018: Journal of Molecular Biology
Michael Z Kamrath, Thomas R Rizzo
Ion mobility spectrometry (IMS) has become a valuable tool in biophysical and bioanalytical chemistry because of its ability to separate and characterize the structure of gas-phase biomolecular ions on the basis of their collisional cross section (CCS). Its importance has grown with the realization that in many cases, biomolecular ions retain important structural characteristics when produced in the gas phase by electrospray ionization (ESI). While a CCS can help distinguish between structures of radically different types, one cannot expect a single number to differentiate similar conformations of a complex molecule...
May 10, 2018: Accounts of Chemical Research
Abhishek Dey, Shaunak Sen
Mathematical methods provide useful framework for the analysis and design of complex systems. In newer contexts such as biology, however, there is a need to both adapt existing methods as well as to develop new ones. Using a combination of analytical and computational approaches, the authors adapt and develop the method of describing functions to represent the input-output responses of biomolecular signalling systems. They approximate representative systems exhibiting various saturating and hysteretic dynamics in a way that is better than the standard linearisation...
June 2018: IET Systems Biology
Tejaswini S Kale, John D Tovar
Peptides provide a biomolecular scaffold for solubilizing and assembling π-conjugated molecules in aqueous media. The properties of such peptide-π chromophore conjugates can be manipulated by varying the constituent amino acid residues in the peptide backbone as well as the chromophore moieties. Such a precise handle on molecular structure leads to molecules with diverse macromolecular and material properties. We developed a versatile synthetic protocol that leads to a wide range of peptide-π chromophore conjugates in which the chromophores are covalently attached to the peptide backbone such that the chromophore is flanked by two peptide chains...
2018: Methods in Molecular Biology
Kwang-Im Oh, Carlos R Baiz
Up to 40% of intracellular water is confined due to the dense packing of macromolecules, ions, and osmolytes. Despite the large body of work concerning the effect of additives on biomolecular structure and stability, the role of crowding and heterogeneity is not well understood. Here, infrared spectroscopy and molecular dynamics simulations are used to describe the mechanisms by which crowding modulates hydrogen bonding interactions between water and dimethyl sulfoxide (DMSO). Specifically, we use formamide and dimethylformamide (DMF) as molecular crowders and show that S=O hydrogen bond populations in aqueous mixtures are increased by both amides...
May 9, 2018: Journal of Physical Chemistry. B
Akash Parvatikar, Gabriel S Vacaliuc, Arvind Ramanathan, S Chakra Chennubhotla
Anharmonicity in time-dependent conformational fluctuations is noted to be a key feature of functional dynamics of biomolecules. Although anharmonic events are rare, long-timescale (μs-ms and beyond) simulations facilitate probing of such events. We have previously developed quasi-anharmonic analysis to resolve higher-order spatial correlations and characterize anharmonicity in biomolecular simulations. In this article, we have extended this toolbox to resolve higher-order temporal correlations and built a scalable Python package called anharmonic conformational analysis (ANCA)...
May 8, 2018: Biophysical Journal
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