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https://www.readbyqxmd.com/read/29792877/coordinating-multi-protein-mismatch-repair-by-managing-diffusion-mechanics-on-the-dna
#1
REVIEW
Daehyung Kim, Richard Fishel, Jong-Bong Lee
DNA mismatch repair (MMR) corrects DNA base pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic molecular coordination of sequential downstream pathways. The temporal and mechanistic order of molecular events is essential to insure interactions in MMR that occur over long distances on the DNA. Biophysical real-time studies of highly conserved components on mismatched DNA have shed light on the mechanics of MMR. Single-molecule imaging has visualized stochastically coordinated MMR interactions that are based on thermal fluctuation-driven motions...
May 21, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29791899/national-practice-patterns-for-prenatal-monitoring-in-gastroschisis-gastroschisis-outcomes-of-delivery-good-provider-survey
#2
Ruchi Amin, Aaron Domack, Joseph Bartoletti, Erika Peterson, Britton Rink, Jennifer Bruggink, Melissa Christensen, Anthony Johnson, William Polzin, Amy J Wagner
BACKGROUND: Gastroschisis is an abdominal wall defect with increasing incidence. Given the lack of surveillance guidelines among maternal-fetal medicine (MFM) specialists, this study describes current practices in gastroschisis management. MATERIALS AND METHODS: An online survey was administered to MFM specialists from institutions affiliated with the North American Fetal Therapy Network (NAFTNet). Questions focused on surveillance timing, testing, findings that changed clinical management, and delivery plan...
May 23, 2018: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/29791480/complex-interactions-in-a-novel-scn5a-compound-mutation-associated-with-long-qt-and-brugada-syndrome-implications-for-na-channel-blocking-pharmacotherapy-for-de-novo-conduction-disease
#3
Jie Liu, Jason D Bayer, Roozbeh Aschar-Sobbi, Marianne Wauchop, Danna Spears, Michael Gollob, Edward J Vigmond, Robert Tsushima, Peter H Backx, Vijay S Chauhan
BACKGROUND: The SCN5A mutation, P1332L, is linked to a malignant form of congenital long QT syndrome, type 3 (LQT3), and affected patients are highly responsive to the Na+ channel blocking drug, mexiletine. In contrast, A647D is an atypical SCN5A mutation causing Brugada syndrome. An asymptomatic male with both P1332L and A647D presented with varying P wave/QRS aberrancy and mild QTc prolongation which did not shorten measurably with mexiletine. OBJECTIVE: We characterized the biophysical properties of P1332L, A647D and wild-type (WT) Na+ channels as well as their combinations in order to understand our proband's phenotype and to guide mexilitine therapy...
2018: PloS One
https://www.readbyqxmd.com/read/29791209/binding-of-intercellular-adhesion-molecule-1-to-%C3%AE-2-integrin-regulates-distinct-cell-adhesion-on-hepatic-and-cerebral-endothelium
#4
Chun-Fang Tong, Yan Zhang, Shou-Qin Lü, Ning Li, Yi-Xin Gong, Hao Yang, Shi-Liang Feng, Yu Du, Dan-Dan Huang, Mian Long
Flowing neutrophils (PMNs) are forced to recruit towards inflamed tissue and adhere on vascular endothelial cells, which is primarily mediated by the binding of β2 -integrins to ICAM-1s. This process is distinct among different organs such as liver and brain, however, the underlying kinetic and mechanical mechanisms regulating tissue-specific recruitment of PMNs remain unclear. Here binding kinetics measurement showed that, ICAM-1 on murine hepatic sinusoidal endothelial cells (LSECs) bound to lymphocyte function-associated antigen-1 (LFA-1) with higher on- and off-rates but lower effective affinity compared to macrophage-1 antigen (Mac-1), while ICAM-1 on cerebral endothelial cells (BMECs or bEnd...
May 23, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29790812/-express-nav1-7-is-phosphorylated-by-fyn-tyrosine-kinase-which-modulates-channel-expression-and-gating-in-a-cell-type-dependent-manner
#5
Yangyang Li, Tengteng Zhu, Huan Yang, Sulayman Dib-Hajj, Stephen Waxman, Ye Yu, Tian-Le Xu, Xiaoyang Cheng
Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, a Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29789067/engineering-aspects-of-protein-interactions-and-self-assembly
#6
Miriam Linsenmeier, Paolo Arosio
In the new Laboratory for Biochemical Engineering (LBCE) at ETH Zurich researchers combine principles of chemical engineering with microfluidic technology and biophysical methods to investigate the physical determinants of biomolecular self-assembly in living organisms. In this account, we show the impact of this activity on concrete applications in biomedical sciences and biotechnology. We focus in particular on the field of protein aggregation and phase separation, and we highlight examples in the context of diagnosis and treatment of Alzheimer's disease and neurodegenerative disorders, cell compartmentalization as well as manufacturing and delivery of therapeutic proteins...
May 30, 2018: Chimia
https://www.readbyqxmd.com/read/29789065/towards-a-synthetic-mitochondrion
#7
Olivier Biner, Thomas Schick, Aymar Abel Ganguin, Christoph von Ballmoos
Our group at the University of Bern uses biochemical and biophysical techniques to unravel details of the molecular mechanism of membrane proteins. Of special interest are the large multi-subunit complexes of the universally conserved respiratory chain and the ATP synthase that are found in mitochondria and aerobic bacteria. In a bottom-up approach using purified membrane proteins and synthetic lipids, we aim to mimic the basic processes of oxidative phosphorylation. We further develop methodologies to increase the complexity of such artificial systems, paving the way for a synthetic mitochondrion...
May 30, 2018: Chimia
https://www.readbyqxmd.com/read/29788887/designing-peptidomimetics
#8
Juan J Perez
The concept of a peptidomimetic was coined about forty years ago. Since then, an enormous effort and interest has been devoted to mimic the properties of peptides with small molecules or pseudopeptides. The present report aims to review different approaches described in the past to succeed in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry approach, where parts of the peptide are successively replaced by non-peptide moieties until getting a non-peptide molecule and a biophysical approach, where a hypothesis of the bioactive form of the peptide is sketched and peptidomimetics are designed based on hanging the appropriate chemical moieties on diverse scaffolds...
May 21, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29788158/cell-wall-bound-silicon-optimizes-ammonium-uptake-and-metabolism-in-rice-cells
#9
Huachun Sheng, Jie Ma, Junbao Pu, Lijun Wang
Background and Aims: Turgor-driven plant cell growth depends on cell wall structure and mechanics. Strengthening of cell walls on the basis of an association and interaction with silicon (Si) could lead to improved nutrient uptake and optimized growth and metabolism in rice (Oryza sativa). However, the structural basis and physiological mechanisms of nutrient uptake and metabolism optimization under Si assistance remain obscure. Methods: Single-cell level biophysical measurements, including in situ non-invasive micro-testing (NMT) of NH4+ ion fluxes, atomic force microscopy (AFM) of cell walls, and electrolyte leakage and membrane potential, as well as whole-cell proteomics using isobaric tags for relative and absolute quantification (iTRAQ), were performed...
May 16, 2018: Annals of Botany
https://www.readbyqxmd.com/read/29787971/cellular-mechanisms-of-physicochemical-membrane-homeostasis
#10
REVIEW
Robert Ernst, Stephanie Ballweg, Ilya Levental
Biological membranes are vital, active contributors to cell function. In addition to specific interactions of individual lipid molecules and lateral organization produced by membrane domains, the bulk physicochemical properties of biological membranes broadly regulate protein structure and function. Therefore, these properties must be homeostatically maintained within a narrow range that is compatible with cellular physiology. Although such adaptiveness has been known for decades, recent observations have dramatically expanded its scope by showing the breadth of membrane properties that must be maintained, and revealing the remarkable diversity of biological membranes, both within and between cell types...
May 19, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29787761/biophysical-studies-and-modelling-indicate-the-binding-preference-of-taz-ww-domain-for-lats1-ppxy-motif
#11
Apoorva Verma, Fu Lin, Tan Ying Chong, Muhammad Nur Hidayat, Chacko Jobichen, Hao Fan, J Sivaraman
The Hippo tumor suppressor pathway is an important regulator of cell proliferation and apoptosis, and signal transduction occurs through phosphorylation of the effector protein TAZ by the serine/threonine kinase LATS1/2. Here, we report the biophysical and computational studies to characterize the interaction between TAZ and LATS1/2 through WW domain-PPxY motif binding. We show that the TAZ WW domain exhibits a binding preference for the second of the two PPxY motifs of LATS1 in vitro. We modelled the structure of the domain in complex with LATS1 PPxY2 peptide and, through molecular dynamics simulations, show that WW domain-PPxY2 complex is stable with some flexibility in the peptide region...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29786776/a-framework-for-image-based-modeling-of-acute-myocardial-ischemia-using-intramurally-recorded-extracellular-potentials
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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