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https://www.readbyqxmd.com/read/29786776/a-framework-for-image-based-modeling-of-acute-myocardial-ischemia-using-intramurally-recorded-extracellular-potentials
#1
Brett M Burton, Kedar K Aras, Wilson W Good, Jess D Tate, Brian Zenger, Rob S MacLeod
The biophysical basis for electrocardiographic evaluation of myocardial ischemia stems from the notion that ischemic tissues develop, with relative uniformity, along the endocardial aspects of the heart. These injured regions of subendocardial tissue give rise to intramural currents that lead to ST segment deflections within electrocardiogram (ECG) recordings. The concept of subendocardial ischemic regions is often used in clinical practice, providing a simple and intuitive description of ischemic injury; however, such a model grossly oversimplifies the presentation of ischemic disease-inadvertently leading to errors in ECG-based diagnoses...
May 21, 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29786613/biophysics-of-membrane-curvature-remodeling-at-molecular-and-mesoscopic-lengthscales
#2
Natesan Ramakrishnan, Ryan P Bradley, Richard W Tourdot, Ravi Radhakrishnan
At the micron scale, where cell organelles display an amazing complexity in their shape and organization, the physical properties of a biological membrane can be better-understood using continuum models subject to thermal (stochastic) undulations. Yet, the chief orchestrators of these complex and intriguing shapes are a specialized class of membrane associating often peripheral proteins called curvature remodeling proteins (CRPs) that operate at the molecular level through specific protein-lipid interactions...
May 22, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29786509/-targeted-screening-for-pre-eclampsia-in-the-first-trimester-of-pregnancy-at-toulouse-university-hospital
#3
A Genoux, P Guerby, M Morin, B Perret, C Vayssière, S M Hamdi
GOALS: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality. Early treatment by aspirin has been shown to significantly reduce PE risk before 37weeks supporting the implementation of first-trimester screening. SUBJECTS AND METHODS: A targeted screening was recently implemented at Toulouse University Hospital for women in their first pregnancy or those with personal or familial history of PE. It uses Fetal Medicine Foundation (FMF) algorithm that combines maternal characteristics, clinical, biophysical and biochemical (PAPP-A, Pregnancy Associated Plasma Protein-A, and PlGF, Placental Growth Factor) data...
May 18, 2018: Annales de Cardiologie et D'angéiologie
https://www.readbyqxmd.com/read/29784830/structural-basis-of-o-glcnac-recognition-by-mammalian-14-3-3-proteins
#4
Clifford A Toleman, Maria A Schumacher, Seok-Ho Yu, Wenjie Zeng, Nathan J Cox, Timothy J Smith, Erik J Soderblom, Amberlyn M Wands, Jennifer J Kohler, Michael Boyce
O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784789/ck1%C3%AE-%C3%AE%C2%B5-protein-kinase-primes-the-per2-circadian-phosphoswitch
#5
Rajesh Narasimamurthy, Sabrina R Hunt, Yining Lu, Jean-Michel Fustin, Hitoshi Okamura, Carrie L Partch, Daniel B Forger, Jae Kyoung Kim, David M Virshup
Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783123/sequentially-distant-but-structurally-similar-proteins-exhibit-fold-specific-patterns-based-on-their-biophysical-properties
#6
Senthilnathan Rajendran, Arunachalam Jothi
The Three-dimensional structure of a protein depends on the interaction between their amino acid residues. These interactions are in turn influenced by various biophysical properties of the amino acids. There are several examples of proteins that share the same fold but are very dissimilar at the sequence level. For proteins to share a common fold some crucial interactions should be maintained despite insignificant sequence similarity. Since the interactions are because of the biophysical properties of the amino acids, we should be able to detect descriptive patterns for folds at such a property level...
May 16, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29782993/generalized-recurrent-neural-network-accommodating-dynamic-causal-modeling-for-functional-mri-analysis
#7
Yuan Wang, Yao Wang, Yvonne W Lui
Dynamic Causal Modeling (DCM) is an advanced biophysical model which explicitly describes the entire process from experimental stimuli to functional magnetic resonance imaging (fMRI) signals via neural activity and cerebral hemodynamics. To conduct a DCM study, one needs to represent the experimental stimuli as a compact vector-valued function of time, which is hard in complex tasks such as book reading and natural movie watching. Deep learning provides the state-of-the-art signal representation solution, encoding complex signals into compact dense vectors while preserving the essence of the original signals...
May 18, 2018: NeuroImage
https://www.readbyqxmd.com/read/29782945/advances-in-the-slow-freezing-cryopreservation-of-microencapsulated-cells
#8
REVIEW
H Gurruchaga, L Saenz Del Burgo, R M Hernandez, G Orive, C Selden, B Fuller, J Ciriza, J L Pedraz
Over the past few decades, the use of cell microencapsulation technology has been promoted for a wide range of applications as sustained drug delivery systems or as cells containing biosystems for regenerative medicine. However, difficulty in their preservation and storage has limited their availability to healthcare centers. Because the preservation in cryogenic temperatures poses many biological and biophysical challenges and that the technology has not been well understood, the slow cooling cryopreservation, which is the most used technique worldwide, has not given full measure of its full potential application yet...
May 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29782818/antimicrobial-activity-profiles-of-amphiphilic-xanthone-derivatives-are-a-function-of-their-molecular-oligomerization
#9
Jun-Jie Koh, Shuimu Lin, Yang Bai, Wendy Wan Ling Sin, Thet Tun Aung, Jianguo Li, Verma Chandra, Konstantin Pervushin, Roger W Beuerman, Shouping Liu
Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria. First, oligomer formation by an amphiphilic xanthone, compound 2 (also coded as AM052), was investigated via solution-state nuclear magnetic resonance (NMR) spectroscopy...
May 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29782051/the-novel-sodium-channel-modulator-gs-458967-gs967-is-an-effective-treatment-in-a-mouse-model-of-scn8a-encephalopathy
#10
Erin M Baker, Christopher H Thompson, Nicole A Hawkins, Jacy L Wagnon, Eric R Wengert, Manoj K Patel, Alfred L George, Miriam H Meisler, Jennifer A Kearney
OBJECTIVE: De novo mutations of SCN8A, encoding the voltage-gated sodium channel NaV 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity...
May 21, 2018: Epilepsia
https://www.readbyqxmd.com/read/29781998/making-testing-and-using-potassium-ion-selective-microelectrodes-in-tissue-slices-of-adult-brain
#11
J Christopher Octeau, Guido Faas, Istvan Mody, Baljit S Khakh
Potassium ions significantly contribute to the resting membrane potential of cells and, therefore, extracellular K+ concentration is a crucial regulator of cell excitability. Altered concentrations of extracellular K+ affect the resting membrane potential and cellular excitability by shifting the equilibria between closed, open and inactivated states for voltage-dependent ion channels that underlie action potential initiation and conduction. Hence, it is valuable to directly measure extracellular K+ dynamics in health and diseased states...
May 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781517/a-homozygous-scn5a-mutation-associated-with-atrial-standstill-and-sudden-death
#12
Reina Bianca Tan, Ivan Gando, Lei Bu, Frank Cecchin, William Coetzee
BACKGROUND: Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations co-segregating with GJA5 or RYR2 however isolated SCN5A mutations are rare. OBJECTIVE: The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death...
May 21, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29780316/resonance-analysis-as-a-tool-for-characterizing-functional-division-of-layer-5-pyramidal-neurons
#13
Melvin A Felton, Alfred B Yu, David L Boothe, Kelvin S Oie, Piotr J Franaszczuk
Evidence suggests that layer 5 pyramidal neurons can be divided into functional zones with unique afferent connectivity and membrane characteristics that allow for post-synaptic integration of feedforward and feedback inputs. To assess the existence of these zones and their interaction, we characterized the resonance properties of a biophysically-realistic compartmental model of a neocortical layer 5 pyramidal neuron. Consistent with recently published theoretical and empirical findings, our model was configured to have a "hot zone" in distal apical dendrite and apical tuft where both high- and low-threshold Ca2+ ionic conductances had densities 1-2 orders of magnitude higher than anywhere else in the apical dendrite...
2018: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/29780302/unified-bayesian-estimator-of-eeg-reference-at-infinity-rrest-regularized-reference-electrode-standardization-technique
#14
Shiang Hu, Dezhong Yao, Pedro A Valdes-Sosa
The choice of reference for the electroencephalogram (EEG) is a long-lasting unsolved issue resulting in inconsistent usages and endless debates. Currently, both the average reference (AR) and the reference electrode standardization technique (REST) are two primary, apparently irreconcilable contenders. We propose a theoretical framework to resolve this reference issue by formulating both (a) estimation of potentials at infinity, and (b) determination of the reference, as a unified Bayesian linear inverse problem, which can be solved by maximum a posterior estimation...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29779963/action-potential-initiation-propagation-and-cortical-invasion-in-the-hyperdirect-pathway-during-subthalamic-deep-brain-stimulation
#15
Ross W Anderson, AmirAli Farokhniaee, Kabilar Gunalan, Bryan Howell, Cameron C McIntyre
BACKGROUND: High frequency (∼130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. However, numerous questions remain to be addressed on the basic biophysics of hyperdirect pathway stimulation...
May 12, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29778882/insight-into-the-interactions-of-proteinase-inhibitor-alpha-2-macroglobulin-with-hypochlorite-thermal-analysis-and-biophysical-approach
#16
Tooba Siddiqui, Mohammad Khalid Zia, Syed Saqib Ali, Haseeb Ahsan, Fahim Halim Khan
Hypochlorous acid, an active bleaching agent is one of the major oxidants produced by neutrophils under physiological conditions. It is a potent reactive oxygen species (ROS) which causes oxidation of biomolecules. Treatment of proteins with hypochlorite results in direct oxidative damage to proteins. Alpha-2-macroglobulin is a major proteinase inhibitor and it can inhibit proteinase of any kind regardless of specificity and catalytic mechanism. The proteinase-antiproteinase balance plays an important role in mediating inflammation associated tissue destruction...
May 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29778836/interrogation-of-mammalian-protein-complex-structure-function-and-membership-using-genome-scale-fitness-screens
#17
Joshua Pan, Robin M Meyers, Brittany C Michel, Nazar Mashtalir, Ann E Sizemore, Jonathan N Wells, Seth H Cassel, Francisca Vazquez, Barbara A Weir, William C Hahn, Joseph A Marsh, Aviad Tsherniak, Cigall Kadoch
Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex...
May 14, 2018: Cell Systems
https://www.readbyqxmd.com/read/29778739/antenatal-ultrasound-value-in-risk-calculation-for-autism-spectrum-disorder-a-systematic-review-to-support-future-research
#18
REVIEW
Francesca Fulceri, Andrea Guzzetta, Argyro Athanasiadou, Laura Iaconianni, Maria Luisa Scattoni
There is a growing research interest on the antenatal features of children with neurodevelopmental disorders. Indeed, it has been proved that the neurodevelopment is, at least partly, affected by processes occurring in fetal life and that the early neurodevelopmental disorders identification is essential to optimize long-term outcomes. This systematic review aims to summarize findings on antenatal ultrasound data, which are or might be considered early risk indexes of postnatal social impairments. We conducted systematic searches in Pubmed and PsychINFO databases to identify studies including fetal ultrasound measurements and postnatal neurodevelopmental outcome assessment...
May 17, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29777812/exploring-the-intermolecular-interactions-and-contrasting-binding-of-flufenamic-acid-with-hemoglobin-and-lysozyme-a-biophysical-and-docking-insight
#19
Sameer Shakeel Ansari, Imtiyaz Yousuf, Farukh Arjmand, Mohammad Khursheed Siddiqi, Saeeda Naqvi
The intermolecular interaction of flufenamic acid (Hfluf) with two model proteins i.e., hemoglobin and lysozyme was explored using fluorescence, UV-vis, circular dichroism, DLS, and molecular docking techniques. The corroborative spectroscopic techniques suggested efficient binding of Hfluf to both the proteins. The S-V plot in Hb-Hfluf system showed positive deviation highlighting the presence of both static and dynamic quenching. Hence, ground state complex model and sphere of action quenching model were used for the study...
May 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775457/potassium-and-sodium-microdomains-in-thin-astroglial-processes-a-computational-model-study
#20
Kevin Breslin, John Joseph Wade, KongFatt Wong-Lin, Jim Harkin, Bronac Flanagan, Harm Van Zalinge, Steve Hall, Matthew Walker, Alexei Verkhratsky, Liam McDaid
A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle (PsC) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments. In this paper, we develop a multi-compartmental mathematical model which proposes a novel mechanism whereby the flow of cations in thin processes is restricted due to negatively charged membrane lipids which result in the formation of deep potential wells near the dipole heads. These wells restrict the flow of cations to "hopping" between adjacent wells as they transverse the process, and this surface retention of cations will be shown to give rise to the formation of potassium (K+) and sodium (Na+) microdomains at the PsC...
May 18, 2018: PLoS Computational Biology
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