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https://www.readbyqxmd.com/read/28437736/murine-diet-induced-obesity-remodels-cardiac-and-liver-mitochondrial-phospholipid-acyl-chains-with-differential-effects-on-respiratory-enzyme-activity
#1
E Madison Sullivan, Amy Fix, Miranda J Crouch, Genevieve C Sparagna, Tonya N Zeczycki, David A Brown, Saame Raza Shaikh
Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or loss of content in aging and cardiovascular diseases, which is postulated to mechanistically impair mitochondrial function. Less is known about how diet-induced obesity influences cardiac phospholipid acyl chain composition and thus mitochondrial responses. Here we first tested if a high fat diet remodeled murine cardiac mitochondrial phospholipid acyl chain composition and consequently disrupted membrane packing, supercomplex formation and respiratory enzyme activity...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28437628/advanced-biomaterials-and-microengineering-technologies-to-recapitulate-the-stepwise-process-of-cancer-metastasis
#2
REVIEW
Nitish Peela, Danh Truong, Harpinder Saini, Hunghao Chu, Samaneh Mashaghi, Stephanie L Ham, Sunil Singh, Hossein Tavana, Bobak Mosadegh, Mehdi Nikkhah
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies...
April 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/28437199/the-correlation-of-arterial-stiffness-with-biophysical-parameters-and-blood-biochemistry
#3
Anamil M Khiyami, Fiona J Dore, Aytan Mammadova, Richard L Amdur, Sabyasachi Sen
INTRODUCTION: Type 2 diabetes presents with numerous macrovascular and microvascular impairments, which in turn lead to various co-morbidities. Vascular co-morbidities can be seen when examining arterial stiffness (AS), which is a predictor for endothelial health and cardiovascular disease risk. Pulse wave analysis (PWA) and pulse wave velocity (PWV) are two tests that are commonly used to measure AS. Currently, disease states and progression are tracked via blood biochemistry. These gold standards in monitoring diabetes are expensive and need optimization...
February 22, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28437106/allosteric-targeting-of-the-fanconi-anemia-ubiquitin-conjugating-enzyme-ube2t-by-fragment-screening
#4
Francesca E Morreale, Alessio Bortoluzzi, Viduth K Chaugule, Connor Arkinson, Helen Walden, Alessio Ciulli
Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it's overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binders have currently been discovered. Herein we report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro...
April 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28435614/time-resolved-biophysical-approaches-to-nucleocytoplasmic-transport
#5
REVIEW
Francesco Cardarelli
Molecules are continuously shuttling across the nuclear envelope barrier that separates the nucleus from the cytoplasm. Instead of being just a barrier to diffusion, the nuclear envelope is rather a complex filter that provides eukaryotes with an elaborate spatiotemporal regulation of fundamental molecular processes, such as gene expression and protein translation. Given the highly dynamic nature of nucleocytoplasmic transport, during the past few decades large efforts were devoted to the development and application of time resolved, fluorescence-based, biophysical methods to capture the details of molecular motion across the nuclear envelope...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28434999/smfret-experiments-of-the-rna-polymerase-ii-transcription-initiation-complex
#6
REVIEW
Nicole Malkusch, Thilo Dörfler, Julia Nagy, Tobias Eilert, Jens Michaelis
Single-molecule fluorescence and in particular single-molecule Förster Resonance Energy Transfer (smFRET(1)) is a powerful tool to provide real-time information on the dynamic architecture of large macromolecular structures such as eukaryotic transcription initiation complexes. In contrast to other structural biology methods, not only structural details, but dynamics transitions are revealed thus closing in on the underlying molecular mechanisms. Here, we describe a comprehensive quantitative biophysical toolbox which can be used for rigorous analysis of dynamic protein-nucleic acid complexes and is applied to the study of eukaryotic transcription initiation...
April 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28434876/dual-targeting-small-molecule-inhibitors-of-the-staphylococcus-aureus-fmn-riboswitch-disrupt-riboflavin-homeostasis-in-an-infectious-setting
#7
Hao Wang, Paul A Mann, Li Xiao, Charles Gill, Andrew M Galgoci, John A Howe, Artjohn Villafania, Christopher M Barbieri, Juliana C Malinverni, Xinwei Sher, Todd Mayhood, Megan D McCurry, Nicholas Murgolo, Amy Flattery, Matthias Mack, Terry Roemer
Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis...
April 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28434301/an-asp-to-asn-mutation-is-a-toxic-trigger-in-beta-2-microglobulin-structure-and-biophysics
#8
Matteo de Rosa, Levon Halabelian, Alberto Barbiroli, Martino Bolognesi, Vittorio Bellotti, Stefano Ricagno
No abstract text is available yet for this article.
March 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28433789/macromolecular-crowding-for-tailoring-tissue-derived-fibrillated-matrices
#9
Valentina Magno, Jens Friedrichs, Heather M Weber, Marina C Prewitz, Mikhail V Tsurkan, Carsten Werner
Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials characteristics only. In this work, we demonstrate how macromolecular crowding (MMC) - the supplementation of matrix reconstitution media with synthetic or natural macromolecules in ways to create excluded volume effects (EVE) - can be employed for tailoring important structural and biophysical characteristics of kidney-derived fibrillated matrices...
April 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28432958/membrane-fusion-between-baculovirus-budded-virus-enveloped-particles-and-giant-liposomes-generated-using-a-droplet-transfer-method-for-the-incorporation-of-recombinant-membrane-proteins
#10
Misako Nishigami, Takaaki Mori, Masahiro Tomita, Kingo Takiguchi, Kanta Tsumoto
Giant proteoliposomes are generally useful as artificial cell membranes in biochemical and biophysical studies, and various procedures for their preparation have been reported. We present here a novel preparation technique that involves the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles, GUVs) that are generated using the droplet-transfer method, where lipid monolayer-coated water-in-oil microemulsion droplets interact with oil/water interfaces to form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus (Autographa californica nucleopolyhedrovirus) that express recombinant transmembrane proteins on their envelopes...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28432789/probing-protein-flexibility-reveals-a-mechanism-for-selective-promiscuity
#11
Nicolas A Pabon, Carlos J Camacho
Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anti-cancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432336/structure-function-analysis-of-the-dna-binding-domain-of-a-transmembrane-transcriptional-activator
#12
Andreas Schlundt, Sophie Buchner, Robert Janowski, Thomas Heydenreich, Ralf Heermann, Jürgen Lassak, Arie Geerlof, Ralf Stehle, Dierk Niessing, Kirsten Jung, Michael Sattler
The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of the cadBA operon through recruitment of the RNA polymerase (RNAP) to the two cadBA promoter sites, Cad1 and Cad2, which are directly bound by CadC...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#13
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28431265/nucleolar-reorganization-in-response-to-rdna-damage
#14
REVIEW
Marjolein van Sluis, Brian McStay
Nucleoli, sites of ribosome biogenesis, form around nucleolar organizer regions (NORs) comprising rDNA arrays, located on human acrocentric chromosome p-arms. NORs provide an opportunity to investigate the DNA double strand break (DSB) response at highly transcribed, repetitive, essential loci. Targeted introduction of DSBs into rDNA results in ATM-dependent inhibition of RNA-polymerase I transcription, coupled with movement of rDNA from the nucleolar interior to anchoring points at the periphery. Reorganization renders rDNA accessible to repair factors, normally excluded from nucleoli...
April 18, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#15
Changchuan Yin, Stephen S-T Yau
Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28430560/database-centric-method-for-automated-high-throughput-deconvolution-and-analysis-of-kinetic-antibody-screening-data
#16
R Paul Nobrega, Michael Brown, Cody Williams, Chris Sumner, Patricia Estep, Isabelle Caffry, Yao Yu, Heather Lynaugh, Irina Burnina, Asparouh Lilov, Jordan Desroches, John Bukowski, Tingwan Sun, Jonathan P Belk, Kirt Johnson, Yingda Xu
The state-of-the-art industrial drug discovery approach is the empirical interrogation of a library of drug candidates against a target molecule. The advantage of high-throughput kinetic measurements over equilibrium assessments is the ability to measure each of the kinetic components of binding affinity. Although high-throughput capabilities have improved with advances in instrument hardware, three bottlenecks in data processing remain: (1) intrinsic molecular properties that lead to poor biophysical quality in vitro are not accounted for in commercially available analysis models, (2) processing data through a user interface is time-consuming and not amenable to parallelized data collection, and (3) a commercial solution that includes historical kinetic data in the analysis of kinetic competition data does not exist...
April 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28430538/biophysical-comparison-of-diphtheria-and-tetanus-toxins-with-the-formaldehyde-detoxified-toxoids-the-main-components-of-diphtheria-and-tetanus-vaccines
#17
Husam Alsarraf, Emil Dedic, Morten J Bjerrum, Ole Østergaard, Max Per Kristensen, Jesper W Petersen, René Jørgensen
No abstract text is available yet for this article.
April 21, 2017: Virulence
https://www.readbyqxmd.com/read/28429999/beneficial-effects-of-oral-supplementation-with-ovoderm-on-human-skin-physiology-two-pilot-studies
#18
Andrés Aguirre, Erena Gil-Quintana, Marisa Fenaux, Sandra Erdozain, Itziar Sarria
Collagens and hyaluronic acid have long been used in pharmaceuticals and food supplements for the improvement of skin elasticity and hydration. These compounds provide the building blocks of the skin. Ovoderm is an oral supplement obtained from eggshells that contains naturally occurring collagen and glycosaminoglycans, such as hyaluronic acid. We evaluated the efficacy of Ovoderm on skin biophysical parameters related to cutaneous aging such as elasticity, hydration, and pigmentation. Two pilot studies were run to assess the effect of daily oral supplementation with 300 mg Ovoderm on skin parameters...
April 21, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28428839/population-genomics-meet-lagrangian-simulations-oceanographic-patterns-and-long-larval-duration-ensure-connectivity-among-paracentrotus-lividus-populations-in-the%C3%A2-adriatic-and-ionian-seas
#19
Marta Paterno, Marcello Schiavina, Giorgio Aglieri, Jamila Ben Souissi, Elisa Boscari, Renato Casagrandi, Aurore Chassanite, Mariachiara Chiantore, Leonardo Congiu, Giuseppe Guarnieri, Claudia Kruschel, Vesna Macic, Ilaria A M Marino, Chiara Papetti, Tomaso Patarnello, Lorenzo Zane, Paco Melià
Connectivity between populations influences both their dynamics and the genetic structuring of species. In this study, we explored connectivity patterns of a marine species with long-distance dispersal, the edible common sea urchin Paracentrotus lividus, focusing mainly on the Adriatic-Ionian basins (Central Mediterranean). We applied a multidisciplinary approach integrating population genomics, based on 1,122 single nucleotide polymorphisms (SNPs) obtained from 2b-RAD in 275 samples, with Lagrangian simulations performed with a biophysical model of larval dispersal...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28428046/cryoprotectants-a-review-of-the-actions-and-applications-of-cryoprotective-solutes-that-modulate-cell-recovery-from-ultra-low-temperatures
#20
REVIEW
Gloria D Elliott, Shangping Wang, Barry J Fuller
Cryopreservation has become a central technology in many areas of clinical medicine, biotechnology, and species conservation within both plant and animal biology. Cryoprotective agents (CPAs) invariably play key roles in allowing cells to be processed for storage at deep cryogenic Temperatures and to be recovered with high levels of appropriate functionality. As such, these CPA solutes possess a wide range of metabolic and biophysical effects that are both necessary for their modes of action, and potentially complicating for cell biological function...
April 18, 2017: Cryobiology
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