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https://www.readbyqxmd.com/read/28651367/alternative-rna-splicing-associated-with-mammalian-neuronal-differentiation
#1
Jiancheng Liu, Anqi Geng, Xiwei Wu, Ren-Jang Lin, Qiang Lu
Alternative pre-mRNA splicing (AS) produces multiple isoforms of mRNAs and proteins from a single gene. It is most prevalent in the mammalian brain and is thought to contribute to the formation and/or maintenance of functional complexity of the brain. Increasing evidence has documented the significant changes of AS between different regions or different developmental stages of the brain, however, the dynamics of AS and the possible function of it during neural progenitor cell (NPC) differentiation is less well known...
June 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28651246/development-of-a-perfusion-platform-for-dynamic-cultivation-of-in-vitro-skin-models
#2
Kay Strüver, Wolfgang Friess, Sarah Hedtrich
Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering...
June 27, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28651183/investigating-the-effect-of-different-transducer-stiffness-values-on-the-contactin-complex-detachment-by-steered-molecular-dynamics
#3
Parnian Kianfar, Nabiollah Abolfathi, Navid Zarif Karimi
This study investigated the adhesion behavior of Contactin4 (CNTN4), a member of Immunoglobulin Super Family (Ig-SF) of cell adhesion molecules. Contactin4 plays a crucial role in the formation, maintenance, and plasticity of neuronal networks. Contactin in its complex configuration with protein tyrosine phosphatase gamma (PTPRG) was selected for simulation. By utilizing Steered Molecular Dynamics (SMD), the uniaxial force was applied to induce unbinding of the complex, and the force-induced detachment of complex components was probed...
June 2, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28651101/competitive-ligands-facilitate-dissociation-of-the-complex-of-bifunctional-inhibitor-and-protein-kinase
#4
Taavi Ivan, Erki Enkvist, Hedi Sinijarv, Asko Uri
Dissociation of the complex of a ligand and a protein usually follows the kinetic profile of the first order process and the rate of dissociation is not affected by the presence of competitive ligands. We discovered that dissociation of the complex between a bifunctional ligand and a protein kinase (the catalytic subunit of cAMP-dependent protein kinase), an enzyme possessing 2 different substrate binding sites, was accelerated (facilitated) over 50-fold in the presence of competitive ligands at higher concentrations...
June 20, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28650958/dynamics-and-impact-of-homologous-recombination-on-the-evolution-of-legionella-pneumophila
#5
Sophia David, Leonor Sánchez-Busó, Simon R Harris, Pekka Marttinen, Christophe Rusniok, Carmen Buchrieser, Timothy G Harrison, Julian Parkhill
Legionella pneumophila is an environmental bacterium and the causative agent of Legionnaires' disease. Previous genomic studies have shown that recombination accounts for a high proportion (>96%) of diversity within several major disease-associated sequence types (STs) of L. pneumophila. This suggests that recombination represents a potentially important force shaping adaptation and virulence. Despite this, little is known about the biological effects of recombination in L. pneumophila, particularly with regards to homologous recombination (whereby genes are replaced with alternative allelic variants)...
June 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28650854/recent-developments-in-deuterium-oxide-tracer-approaches-to-measure-rates-of-substrate-turnover-implications-for-protein-lipid-and-nucleic-acid-research
#6
Matthew S Brook, Daniel J Wilkinson, Philip J Atherton, Ken Smith
PURPOSE OF REVIEW: Methods that inform on dynamic metabolism that can be applied to clinical populations to understand disease progression and responses to therapeutic interventions are of great importance. This review perspective will highlight recent advances, development, and applications of the multivalent stable isotope tracer deuterium oxide (D2O) to the study of substrate metabolism with particular reference to protein, lipids, and nucleic acids, and how these methods can be readily applied within clinical and pharmaceutical research...
June 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28650689/time-and-dose-dependent-claudin-contribution-to-biological-functions-lessons-from-claudin-1-in-skin
#7
Reitaro Tokumasu, Atsushi Tamura, Sachiko Tsukita
There are many types of biologic compartments in the body. Tight junctions (TJs) function to create a dynamic paracellular barrier to separate these compartments and maintain homeostasis. The TJ component claudin-1 is the major transmembrane protein responsible for forming the paracellular barrier in the epidermis; other claudins in the epidermis include claudin-3, -4, -12, -23 and -25. Accumulating evidence points to a relationship between claudin-1 and skin diseases; for example, a decrease in claudin-1 is reported in human atopic dermatitis...
June 19, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28650657/noncovalent-pegylation-through-protein-polyelectrolyte-interaction-kinetic-experiment-and-molecular-dynamics-simulation
#8
Takaaki Kurinomaru, Kengo Kuwada, Shunsuke Tomita, Tomoshi Kameda, Kentaro Shiraki
Noncovalent binding of polyethylene glycol (PEG) to a protein surface is a unique protein handling technique to control protein function and stability. A diblock copolymer containing PEG and polyelectrolyte chains (PEGylated polyelectrolyte) is a promising candidate for noncovalent attachment of PEG to a protein surface because of the binding through multiple electrostatic interactions without protein denaturation. To obtain a deeper understanding of protein-polyelectrolyte interaction at the molecular level, we investigated the manner in which cationic PEGylated polyelectrolyte binds to anionic α-amylase in enzyme kinetic experiments and molecular dynamics (MD) simulations...
June 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28650599/anti-mullerian-hormone-a-marker-of-upcoming-menopause-or-a-questionable-guesswork
#9
(no author information available yet)
Anti-Müllerian hormone (AMH) is a protein produced by pre-antral and small antral ovarian follicles. It is an acknowledged marker of ovarian reserve and remaining reproductive capacity, commonly used in reproductive medicine. From the third decade of life, AMH serum levels decrease consecutively up to menopause. Since the standardization of commercial assays, novel contributions of that parameter are being observed. Up to date, there is no screening tool for predicting the age of natural menopause (ANM). The following literature review evaluates the utility of AMH measurement in predicting ANM...
May 26, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28650521/jmj27-an-arabidopsis-h3k9-histone%C3%A2-demethylase-modulates-defense-against-pseudomonas-syringae%C3%A2-and%C3%A2-flowering%C3%A2-time
#10
Aditya Dutta, Pratibha Choudhary, Julie Caruana, Ramesh Raina
Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time...
June 26, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28650167/molecular-insight-into-the-adsorption-of-spruce-budworm-antifreeze-protein-to-ice-surface-a-clathrate-mediated-recognition-mechanism
#11
Sandipan Chakraborty, Biman Jana
The principal mechanism of ice recognition by antifreeze protein (AFP) is a topic of intense discussion in recent times. Despite of many experimental and theoretical studies, the detailed understanding of the process remains elusive. Present work aims to explore the molecular mechanism of ice recognition by an insect AFP from Spruce budworm, sbwAFP. Evident from our simulation, water dynamics becomes highly sluggish around the IBS due to the combined effect of confinement and ordering induced by the perfectly aligned methyl side-chains of threonine residues, the THRs ladder...
June 26, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28650060/an-adaptive-bias-hybrid-md-kmc-algorithm-for-protein-folding-and-aggregation
#12
Emanuel K Peter, Joan-Emma Shea
In this paper, we present a novel hybrid Molecular Dynamics/kinetic Monte Carlo (MD/kMC) algorithm and apply it to protein folding and aggregation in explicit solvent. The new algorithm uses a dynamical definition of biases throughout the MD component of the simulation, normalized in relation to the unbiased forces. The algorithm guarantees sampling of the underlying ensemble in dependency of one average linear coupling factor 〈α〉τ. We test the validity of the kinetics in simulations of dialanine and compare dihedral transition kinetics with long-time MD-simulations...
June 26, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28650030/carbon-nanoscroll-silk-crystallite-hybrid-structures-with-controllable-hydration-and-mechanical-properties
#13
Yuan Cheng, Leng-Duei Koh, Fan Wang, Dechang Li, Baohua Ji, Jingjie Yeo, Guijian Guan, Ming-Yong Han, Yong-Wei Zhang
Hybrid structures of nanomaterials (e.g. tubes, scrolls, threads, cages) and biomaterials (e.g. proteins) hold tremendous potential for applications as drug carriers, biosensors, tissue scaffolds, cancer therapeutic agents, etc. However, in many cases, the interacting forces at the nano-bio interfaces and their roles in controlling the structures and dynamics of nano-bio-hybrid systems are very complicated but poorly understood. In this study, we investigate the structure and mechanical behavior of a protein-based hybrid structure, i...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649967/structural-perturbations-on-huntingtin-n17-domain-during-its-folding-on-2d-nanomaterials
#14
Leili Zhang, Mei Feng, Ruhong Zhou, Binquan Luan
A globular protein's folded structure in its physiological environment is largely determined by its amino acid sequence. Recently, newly discovered transformer proteins as well as intrinsically disordered proteins may adopt the folding-upon-binding mechanism where their secondary structures are highly dependent on their binding partners. Due to the various applications of nanomaterials in biological sensors and potential wearable devices, it is important to discover possible conformational changes of proteins on nanomaterials...
June 26, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28649965/pawflim-reducing-bias-and-uncertainty-to-enable-lower-photon-count-in-flim-experiments
#15
Mauro Silberberg, Hernán E Grecco
Förster resonant energy transfer measured by fluorescence lifetime imaging microscopy (FRET-FLIM) is the method of choice for monitoring the spatio-temporal dynamics of protein interactions in living cells. To obtain an accurate estimate of the molecular fraction of interacting proteins requires a large number of photons, which usually precludes the observation of a fast process, particularly with time correlated single photon counting (TCSPC) based FLIM. In this work, we propose a novel method named pawFLIM (phasor analysis via wavelets) that allows the denoising of FLIM datasets by adaptively and selectively adjusting the desired compromise between spatial and molecular resolution...
June 26, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28649424/an-alanine-expanded-pabpn1-causes-increased-utilization-of-intronic-polyadenylation-sites
#16
Tooba Abbassi-Daloii, Soheil Yousefi, Eleonora de Klerk, Laurens Grossouw, Muhammad Riaz, Peter A C 't Hoen, Vered Raz
In eukaryote genomes, the polyadenylation site marks termination of mature RNA transcripts by a poly-adenine tail. The polyadenylation site is recognized by a dynamic protein complex, among which the poly-adenine-binding protein nuclear1 plays a key role. Reduced poly-adenine-binding protein nuclear1 levels are found in aged muscles and are even lower in oculopharyngeal muscular dystrophy patients. Oculopharyngeal muscular dystrophy is a rare, late onset autosomal dominant myopathy, and is caused by an alanine expansion mutation in poly-adenine-binding protein nuclear1...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28649316/discovery-of-decamidine-as-a-new-and-potent-prmt1-inhibitor
#17
Jing Zhang, Kun Qian, Chunli Yan, Maomao He, Brenson A Jassim, Ivaylo Ivanov, Yujun George Zheng
Protein arginine methyltransferase 1 (PRMT1) is a key player for the dynamic regulation of arginine methylation. Its dysregulation and aberrant expression are implicated in various pathological conditions, and a plethora of evidence suggests that PRMT1 inhibition is of significant therapeutic value. Herein, we reported the modification of a series of diamidine compounds with varied lengths in the middle alkyl linker for PRMT1 inhibition. Decamidine (2j), which possesses the longest linker in the series, displayed 2- and 4- fold increase in PRMT1 inhibition (IC50 = 13 μM), as compared with furamdine and stilbamidine...
February 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28648994/dynamic-and-differential-expression-of-the-gonadal-aromatase-during-the-process-of-sexual-differentiation-in-a-novel-transgenic-cyp19a1a-egfp-zebrafish-line
#18
Nathalie Hinfray, Frédéric Sohm, Morgane Caulier, Edith Chadili, Benjamin Piccini, Camille Torchy, Jean-Marc Porcher, Yann Guiguen, François Brion
In zebrafish, there exists a clear need for new tools to study sex differentiation dynamic and its perturbation by endocrine disrupting chemicals. In this context, we developed and characterized a novel transgenic zebrafish line expressing green fluorescent protein (GFP) under the control of the zebrafish cyp19a1a (gonadal aromatase) promoter. In most gonochoristic fish species including zebrafish, cyp19a1a, the enzyme responsible for the synthesis of estrogens, has been shown to play a critical role in the processes of reproduction and sexual differentiation...
June 22, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28648754/what-can-human-guided-simulations-bring-to-rna-folding
#19
Liuba Mazzanti, Sébastien Doutreligne, Cedric Gageat, Philippe Derreumaux, Antoine Taly, Marc Baaden, Samuela Pasquali
Inspired by the recent success of scientific-discovery games for predicting protein tertiary and RNA secondary structures, we have developed an open software for coarse-grained RNA folding simulations, guided by human intuition. To determine the extent to which interactive simulations can accurately predict 3D RNA structures of increasing complexity and lengths (four RNAs with 22-47 nucleotides), an interactive experiment was conducted with 141 participants who had very little knowledge of nucleic acids systems and computer simulations, and had received only a brief description of the important forces stabilizing RNA structures...
June 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28648680/reversibly-constraining-spliceosome-substrate-complexes-by-engineering-disulfide-crosslinks
#20
Patrick McCarthy, Erin Garside, Yonatan Meschede-Krasa, Andrew MacMillan, Daniel Pomeranz Krummel
The spliceosome is a highly dynamic mega-Dalton enzyme, formed in part by assembly of U snRNPs onto its pre-mRNA substrate transcripts. Early steps in spliceosome assembly are challenging to study biochemically and structurally due to compositional and conformational dynamics. We detail an approach to covalently and reversibly constrain or trap non-covalent pre-mRNA/protein spliceosome complexes. This approach involves engineering a single disulfide bond between a thiol-bearing cysteine sidechain and a proximal backbone phosphate of the pre-mRNA, site-specifically modified with an N-thioalkyl moiety...
June 22, 2017: Methods: a Companion to Methods in Enzymology
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