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https://www.readbyqxmd.com/read/28631593/a-denv-2-type-specific-monoclonal-antibody-binds-to-the-denv-complex-reactive-antigenic-site-on-envelope-protein-domain-3
#1
Vanessa V Sarathy, Trevor J Pitcher, Gregory D Gromowski, John T Roehrig, Alan D T Barrett
The Dengue virus (DENV) envelope (E) protein is the major component of the viral surface and is structurally subdivided into three domains, ED1, ED2 and ED3. ED3 elicits potent neutralizing antibodies and contains two major antigenic sites: the DENV-type-specific and DENV-complex-reactive antigenic sites. Each site is composed of a limited subset of residues that are required for monoclonal antibody (mAb) binding. Here we show that DENV-2-type-specific mAb 9A3D-8 utilizes the functionally critical residues K307, V308, K310, I312, P332, L387, L389 and N390 for ED3 binding...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28625864/a-systematic-study-of-the-effect-of-low-ph-acid-treatment-on-anti-drug-antibodies-specific-for-a-domain-antibody-therapeutic-impact-on-drug-tolerance-assay-sensitivity-and-post-validation-method-assessment-of-ada-in-clinical-serum-samples
#2
Uma Kavita, Jia Duo, Sean Crawford, Rong Liu, Joan Valcin, Carol Gleason, Huijin Dong, Snaehal Gadkari, Robert W Dodge, Renuka Pillutla, Binodh S DeSilva
We developed a homogeneous bridging anti-drug antibody (ADA) assay on an electro chemiluminescent immunoassay (ECLIA) platform to support the immunogenicity evaluation of a dimeric domain antibody (dAb) therapeutic in clinical studies. During method development we evaluated the impact of different types of acid at various pH levels on polyclonal and monoclonal ADA controls of differing affinities and on/off rates. The data shows for the first time that acids of different pH can have a differential effect on ADA of various affinities and this in turn impacts assay sensitivity and drug tolerance as defined by these surrogate controls...
June 15, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28624540/cross-%C3%AE-polymerization-and-hydrogel-formation-by-low-complexity-sequence-proteins
#3
Masato Kato, Yi Lin, Steven L McKnight
Low-complexity (LC) sequences, typically believed to be incapable of assuming structural order, are abundant constituents of the proteomes of all eukaryotic organisms. These sequences have emerged as critical components for formation of meso-scaled, sub-cellular organelles not invested by surrounding membranes, exemplified by RNA granules. We have observed that LC domains of many RNA binding proteins known to be constituents of RNA granules readily form labile cross-β polymers under physiological conditions...
June 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28624493/expression-of-the-c-terminal-domain-of-human-apolipoprotein-a-i-using-a-chimeric-apolipoprotein
#4
Daniel E Sallee, James V C Horn, Lukas A Fuentes, Paul M M Weers
Human apolipoprotein A-I (apoA-I) is the most abundant protein in high-density lipoprotein, an anti-atherogenic lipid-protein complex responsible for reverse cholesterol transport. The protein is composed of an N-terminal helix bundle domain, and a small C-terminal (CT) domain. To facilitate study of CT-apoA-I, a novel strategy was employed to produce this small domain in a bacterial expression system. A protein construct was designed of insect apolipophorin III (apoLp-III) and residues 179-243 of apoA-I, with a unique a methionine residue positioned between the two proteins and an N-terminal His-tag to facilitate purification...
June 14, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28623754/quality-of-life-mood-and-seizure-control-in-patients-with-brain-tumor-related-epilepsy-treated-with-lacosamide-as-add-on-therapy-a-prospective-explorative-study-with-a-historical-control-group
#5
Marta Maschio, Alessia Zarabla, Andrea Maialetti, Alessandra Fabi, Antonello Vidiri, Veronica Villani, Diana Giannarelli
OBJECTIVE: Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE...
June 14, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28623092/ctip-ctp1-sae2-molecular-form-fit-for-function
#6
REVIEW
Sara N Andres, R Scott Williams
Vertebrate CtIP, and its fission yeast (Ctp1), budding yeast (Sae2) and plant (Com1) orthologs have emerged as key regulatory molecules in cellular responses to DNA double strand breaks (DSBs). By modulating the nucleolytic 5'-3' resection activity of the Mre11/Rad50/Nbs1 (MRN) DSB repair processing and signaling complex, CtIP/Ctp1/Sae2/Com1 is integral to the channeling of DNA double strand breaks through DSB repair by homologous recombination (HR). Nearly two decades since its discovery, emerging new data are defining the molecular underpinnings for CtIP DSB repair regulatory activities...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28612065/field-effects-to-slow-magnetic-relaxation-in-a-mononuclear-ni-ii-complex
#7
D Lomjanský, J Moncol', C Rajnák, J Titiš, R Boča
A mononuclear Ni(ii) complex [Ni(NCS)2(nqu)2(H2O)2]·2nqu (nqu - 5-nitroquinoline) shows a field induced slow magnetic relaxation with three relaxation domains. The relaxation time for the low-frequency mode is as slow as τ = 0.3 s at T = 1.9 K and BDC = 0.4 T.
June 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28609612/diverse-supramolecular-nanofiber-networks-assembled-by-functional-low-complexity-domains
#8
Bolin An, Xinyu Wang, Mengkui Cui, Xinrui Gui, Xiuhai Mao, Yan Liu, Ke Li, Cenfeng Chu, Jiahua Pu, Susu Ren, Yanyi Wang, Guisheng Zhong, Timothy K Lu, Cong Liu, Chao Zhong
Self-assembling supramolecular nanofibers, common in the natural world, are of fundamental interest and technical importance to both nanotechnology and materials science. Despite important advances, synthetic nanofibers still lack the structural and functional diversity of biological molecules, and the controlled assembly of one type of molecule into a variety of fibrous structures with wide-ranging functional attributes remains challenging. Here, we harness the low-complexity (LC) sequence domain of fused in sarcoma (FUS) protein, an essential cellular nuclear protein with slow kinetics of amyloid fiber assembly, to construct random copolymer-like, multi-block and self-sorted supramolecular fibrous networks with distinct structural features and fluorescent functionalities...
June 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28608348/identification-and-analysis-of-wg-gw-argonaute-binding-domains
#9
Andrzej Zielezinski, Wojciech M Karlowski
WG/GW domains recruit ARGONAUTE (AGO) proteins to distinct silencing effector complexes using combinations of just two amino acids: tryptophan (W) and glycine (G), forming a wide arsenal of highly simplified interaction surfaces. These unstructured domains exhibit very low sequence identity and excessive length polymorphism, which makes identification of new AGO-binding proteins a challenging task as they escape detection with standard sequence comparison-based methods (e.g., BLAST, HMMER).In this chapter, we explain the use of tools for prediction of AGO-binding WG/GW domains in protein sequences...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28604741/a-novel-nuclear-complex-of-drr1-f-actin-and-commd1-involved-in-nf-%C3%AE%C2%BAb-degradation-and-cell-growth-suppression-in-neuroblastoma
#10
P Mu, T Akashi, F Lu, S Kishida, K Kadomatsu
Downregulated in renal cell carcinoma 1 (DRR1) has important roles in tumor cell growth, neuron survival and spine formation, and was recently shown to bind actin. However, the roles of nuclear DRR1 remain largely unexplored. Here, we identified an interaction between filamentous actin (F-actin) and DRR1 in the nucleus, and demonstrated that copper metabolism MURR1 domain-containing 1 (COMMD1) is another binding partner of DRR1. Accordingly, DRR1, F-actin and COMMD1 were shown to form a complex in the nucleus, and the stability of COMMD1 was enhanced in this complex...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28602352/cryo-em-reveals-how-human-cytoplasmic-dynein-is-auto-inhibited-and-activated
#11
Kai Zhang, Helen E Foster, Arnaud Rondelet, Samuel E Lacey, Nadia Bahi-Buisson, Alexander W Bird, Andrew P Carter
Cytoplasmic dynein-1 binds dynactin and cargo adaptor proteins to form a transport machine capable of long-distance processive movement along microtubules. However, it is unclear why dynein-1 moves poorly on its own or how it is activated by dynactin. Here, we present a cryoelectron microscopy structure of the complete 1.4-megadalton human dynein-1 complex in an inhibited state known as the phi-particle. We reveal the 3D structure of the cargo binding dynein tail and show how self-dimerization of the motor domains locks them in a conformation with low microtubule affinity...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28601703/controlled-and-sustained-delivery-of-sirna-nps-from-hydrogels-expedites-bone-fracture-healing
#12
Yuchen Wang, Dominic W Malcolm, Danielle S W Benoit
Despite great potential, delivery remains as the most significant barrier to the widespread use of siRNA therapeutics. siRNA has delivery limitations due to susceptibility to RNase degradation, low cellular uptake, and poor tissue-specific localization. Here, we report the development of a hybrid nanoparticle (NP)/hydrogel system that overcomes these challenges. Hydrogels provide localized and sustained delivery via controlled release of entrapped siRNA/NP complexes while NPs protect and enable efficient cytosolic accumulation of siRNA...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28601115/modeling-change-in-project-duration-and-completion-scheduling-dynamics-of-nasa-s-exploration-flight-test-1-eft-1-activities
#13
Travis J Wiltshire, Jonathan E Butner, Zachary Pirtle
In complex work domains and organizations, understanding schedule-ing dynamics can ensure objectives are reached and delays are mitigated. In the current paper, we examine the scheduling dynamics for NASA's Exploration Flight Test 1 (EFT-1) activities. For this examination, we specifically modeled simultaneous change in percent complete and estimated duration for a given project as they were included in monthly reports over time. In short, we utilized latent change score mixture modeling to extract the attractor dynamics within the scheduling data...
July 2017: Nonlinear Dynamics, Psychology, and Life Sciences
https://www.readbyqxmd.com/read/28600106/genetic-analysis-of-mayer-rokitansky-kuster-hauser-syndrome-in-a-large-cohort-of-families
#14
Lacey S Williams, Durkadin Demir Eksi, Yiping Shen, Amy C Lossie, Lynn P Chorich, Megan E Sullivan, John A Phillips, Munire Erman, Hyung-Goo Kim, Ozgul M Alper, Lawrence C Layman
OBJECTIVE: To study the genetic cause of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). Although a few candidate genes and genomic domains for have been reported for MRKH, the genetic underpinnings remain largely unknown. Some of the top candidate genes are WNT4, HNF1B, and LHX1. The goals of this study were to: 1) determine the prevalence of WNT4, HNF1B, and LHX1 point mutations, as well as new copy number variants (CNVs) in people with MRKH; and 2) identify and characterize MRKH cohorts...
June 6, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28592293/plasmobase-a-comparative-database-of-predicted-domain-architectures-for-plasmodium-genomes
#15
Juliana Bernardes, Catherine Vaquero, Alessandra Carbone
BACKGROUND: With the availability of complete genome sequences of both human and non-human Plasmodium parasites, it is now possible to use comparative genomics to look for orthology across Plasmodium species and for species specific genes. This comparative analyses could provide important clues for the development of new strategies to prevent and treat malaria in humans, however, the number of functionally annotated proteins is still low for all Plasmodium species. In the context of genomes that are hard to annotate because of sequence divergence, such as Plasmodium, domain co-occurrence becomes particularly important to trust predictions...
June 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28583164/health-professionals-views-on-the-barriers-and-enablers-to-evidence-based-practice-for-acute-stroke-care-a-systematic-review
#16
REVIEW
Leonard Baatiema, Michael E Otim, George Mnatzaganian, Ama de-Graft Aikins, Judith Coombes, Shawn Somerset
BACKGROUND: Adoption of contemporary evidence-based guidelines for acute stroke management is often delayed due to a range of key enablers and barriers. Recent reviews on such barriers focus mainly on specific acute stroke therapies or generalised stroke care guidelines. This review examined the overall barriers and enablers, as perceived by health professionals which affect how evidence-based practice guidelines (stroke unit care, thrombolysis administration, aspirin usage and decompressive surgery) for acute stroke care are adopted in hospital settings...
June 5, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/28581722/the-pipx-protein-when-not-bound-to-its-targets-has-its-signaling-c-terminal-helix-in-a-flexed-conformation
#17
Alicia Forcada-Nadal, Martina Palomino-Schätzlein, José L Neira, Antonio Pineda-Lucena, Vicente Rubio
PipX, an 89-residue protein, acts as a coactivator of the global nitrogen regulator NtcA in cyanobacteria. NtcA-PipX interactions are regulated by 2-oxoglutarate (2-OG), an inverse indicator of the ammonia abundance, and by PII, a protein that binds to PipX at low 2-OG concentrations. The structure of PipX, when bound to NtcA or PII, consists of an N-terminal, five-stranded β-sheet (conforming a Tudor-like domain), and two long α-helices. These helices adopt either a flexed conformation, where they are in close contact and in an antiparallel mutual orientation, also packing against the β-sheet, or an open conformation (observed only in the PII-PipX complex) where the last α-helix moves apart from the rest of the protein...
June 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28575276/structural-determinants-of-apobec3b-non-catalytic-domain-for-molecular-assembly-and-catalytic-regulation
#18
Xiao Xiao, Hanjing Yang, Vagan Arutiunian, Yao Fang, Guillaume Besse, Cherie Morimoto, Brett Zirkle, Xiaojiang S Chen
The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B...
May 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28569241/atrial-fibrillation-detection-on-compressed-sensed-ecg
#19
Giulia Da Poian, Chengyu Liu, Riccardo Bernardini, Roberto Rinaldo, Gari Clifford
OBJECTIVE: Compressive Sensing (CS) approaches to electrocardiogram (ECG) analysis provide efficient methods for real time encoding of cardiac activity. In doing so, it is important to assess the downstream effect of the compression on any signal processing and classification algorithms. CS is particularly suitable for low power wearable devices, thanks to its low-complex digital or hardware implementation that directly acquires a compressed version of the signal through random projections...
June 1, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28550061/the-lectin-chaperone-calnexin-is-involved-in-endoplasmic-reticulum-stress-response-by-regulating-ca-2-homeostasis-in-aspergillus-nidulans
#20
Shenghua Zhang, Hailin Zheng, Qiuyi Chen, Yuan Chen, Sha Wang, Ling Lu, Shizhu Zhang
The Ca(2+)-mediated signaling pathway is crucial for environmental adaptation in fungi. Here we show that calnexin, a molecular chaperone located in the endoplasmic reticulum (ER), plays an important role in regulating cytosolic free calcium concentration ([Ca(2+)]c) in Aspergillus nidulans Inactivation of calnexin (ClxA) in A. nidulans caused severe defects in hyphal growth and conidiation under ER stress caused by the ER-stress inducing agent dithiothreitol (DTT) or high temperature. Importantly, defects in the ΔclxA mutant were restored by the addition of extracellular calcium...
May 26, 2017: Applied and Environmental Microbiology
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