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https://www.readbyqxmd.com/read/28823097/epitope-mapping-of-histo-blood-group-antigens-bound-to-norovirus-vlps-using-std-nmr-experiments-reveals-fine-details-of-molecular-recognition
#1
Brigitte Fiege, Mila Leuthold, Francisco Parra, Kevin P Dalton, Peter J Meloncelli, Todd L Lowary, Thomas Peters
Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be critical for the infection process. Therefore, we have determined binding epitopes of synthetic type 1 to 6 blood group A- and B-tetrasaccharides binding to GII.4 human Norovirus virus like particles (VLPs) using STD NMR experiments. So far, little information is available from crystal structure analysis studies on the interactions of the reducing-end sugars with the protruding domain (P-domain) of the viral coat protein VP1...
August 19, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28822610/evaluation-of-fever-in-the-emergency-department
#2
REVIEW
Sarah DeWitt, Summer A Chavez, Jack Perkins, Brit Long, Alex Koyfman
BACKGROUND: Fever is one of the most common complaints in the emergency department (ED) and is more complex than generally appreciated. The broad differential diagnosis of fever includes numerous infectious and non-infectious etiologies. An essential skill in emergency medicine is recognizing the pitfalls in fever evaluation. OBJECTIVE OF REVIEW: This review provides an overview of the complaint of fever in the ED to assist the emergency physician with a structured approach to evaluation...
August 14, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28822125/in-vitro-alkylation-methods-for-assessing-the-protein-redox-state
#3
Flavien Zannini, Jérémy Couturier, Olivier Keech, Nicolas Rouhier
Cysteines are important residues for protein structure, function, and regulation. Owing to their modified reactivity, some cysteines can undergo very diverse redox posttranslational modifications, including the reversible formation of disulfide bonds, a widespread protein regulatory process as well exemplified in plant chloroplasts for Calvin-Benson cycle enzymes. Both core- and peripheral-photorespiratory enzymes possess conserved cysteines, some of which have been identified as being subject to oxidative modifications...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28821863/the-heat-shock-response-and-humoral-immune-response-are-mutually-antagonistic-in-honey-bees
#4
Mia McKinstry, Charlie Chung, Henry Truong, Brittany A Johnston, Jonathan W Snow
The honey bee is of paramount importance to humans in both agricultural and ecological settings. Honey bee colonies have suffered from increased attrition in recent years, stemming from complex interacting stresses. Defining common cellular stress responses elicited by these stressors represents a key step in understanding potential synergies. The proteostasis network is a highly conserved network of cellular stress responses involved in maintaining the homeostasis of protein production and function. Here, we have characterized the Heat Shock Response (HSR), one branch of this network, and found that its core components are conserved...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821652/calpain-grip-signaling-in-nucleus-accumbens-core-mediates-the-reconsolidation-of-drug-reward-memory
#5
Jie Liang, Jia-Li Li, Ying Han, Yi-Xiao Luo, Yan-Xue Xue, Yàn Zhang, Yán Zhang, Li-Bo Zhang, Man-Li Chen, Lin Lu, Jie Shi
Exposure to drug-paired cues causes drug memories to be in a destabilized state, and interfering with memory reconsolidation can inhibit relapse. Calpain, a calcium-dependent neutral cysteine protease, is involved in synaptic plasticity and the formation of long-term fear memory. However, the role of calpain in the reconsolidation of drug reward memory is still unknown. In the present study, using conditioned place preference (CPP) model, we found that exposure to drug-paired contextual stimuli induced the activation of calpain and decreased the expression of glutamate receptor interacting protein 1 (GRIP1) in the nucleus accumbens (NAc) core but not shell of male rats...
August 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821611/the-proteasome-interacting-ecm29-protein-disassembles-the-26s-proteasome-in-response-to-oxidative-stress
#6
Xiaorong Wang, Ilan E Chemmama, Clinton Yu, Alexander Huszagh, Yue Xu, Rosa Viner, Sarah Ashley Block, Peter Cimermancic, Scott D Rychnovsky, Yihong Ye, Andrej Sali, Lan Huang
Oxidative stress has been implicated in multiple human neurological and other disorders. Proteasomes are multi-subunit proteases critical for the removal of oxidatively damaged proteins. To understand stress-associated human pathologies, it is important to uncover the molecular events underlying the regulation of proteasomes upon oxidative stress. To this end, we investigated H2O2 stress-induced molecular changes of the human 26S proteasome and determined that stress-induced 26S proteasome disassembly is conserved from yeast to human...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821545/heterologous-production-of-thermophile-thermochromatium-tepidum-photosynthetic-reaction-centre-and-light-harvesting-1-complexes-in-the-mesophile-rhodobacter-sphaeroides-and-thermal-stabilities-of-a-hybrid-core-complex
#7
D Jun, V Huang, J T Beatty
The photosynthetic complexes of the thermophile Thermochromatium tepidum are of considerable interest in biohybrid solar cell applications because of the capability of thermophilic proteins to tolerate elevated temperatures. Synthetic operons encoding reaction centre (RC) and light harvesting 1 (LH1) pigment-protein complexes of T. tepidum were expressed in the mesophile Rhodobacter sphaeroides The T. tepidum RC (TRC) was assembled, and functional with the addition of menadione to populate the QA pocket. The production of the T...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28820893/a-computational-method-for-the-identification-of-candidate-drugs-for-non-small-cell-lung-cancer
#8
Lei Chen, Jing Lu, Tao Huang, Yu-Dong Cai
Lung cancer causes a large number of deaths per year. Until now, a cure for this disease has not been found or developed. Finding an effective drug through traditional experimental methods invariably costs millions of dollars and takes several years. It is imperative that computational methods be developed to integrate several types of existing information to identify candidate drugs for further study, which could reduce the cost and time of development. In this study, we tried to advance this effort by proposing a computational method to identify candidate drugs for non-small cell lung cancer (NSCLC), a major type of lung cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#9
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
August 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28820582/pathogenic-mutations-induce-partial-structural-changes-in-native-%C3%AE-sheet-structure-of-transthyretin-and-accelerate-aggregation
#10
Kwang Hun Lim, Anvesh K R Dasari, Renze Ma, Ivan Hung, Zhehong Gan, Jeffery W Kelly, Michael C Fitzgerald
Amyloid formation of natively folded proteins involves global and/or local unfolding of the native state to form aggregation-prone intermediates. Here we report solid-state NMR structural studies of amyloid derived from wild-type (WT) and more aggressive mutant forms of transthyretin (TTR) to investigate the structural changes associated with effective TTR aggregation. We employed selective 13C-labeling schemes to investigate structural features of β-structured core regions in amyloid states of WT and two mutant forms (V30M and L55P) of TTR...
August 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28820389/hippo-pathway-brief-overview-of-its-relevance-in-cancer
#11
A L Zygulska, K Krzemieniecki, P Pierzchalski
The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819289/escrt-iii-membrane-trafficking-misregulation-contributes-to-fragile-x-syndrome-synaptic-defects
#12
Dominic J Vita, Kendal Broadie
The leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818232/review-of-the-endothelial-pathogenic-mechanism-of-tie2-related-venous-malformation
#13
REVIEW
Zhong Du, JiaWei Zheng, ZhiYuan Zhang, YanAn Wang
BACKGROUND: Venous malformation (VM) is a type of disease involving vascular morphogenesis in humans. Clinically, VM can be sporadic or inherited. TIE2, also known as TEK or HYK, is a member of the receptor tyrosine kinase subfamily and is highly conserved among species. In 1996, an arginine-to-tryptophan substitution at position 849 (R849W) in TIE2 was found to induce hereditary VM. Additional alterations in TIE2 involved in the pathogenesis of inherited or sporadic VM have since been reported...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28816462/-1-h-detected-redor-with-fast-magic-angle-spinning-of-a-deuterated-protein
#14
Manali Ghosh, Chad M Rienstra
Rotational echo double resonance (REDOR) is a highly successful method for heteronuclear distance determination in biological solid-state NMR, and 1H detection methods have emerged in recent years as a powerful approach to improving sensitivity and resolution for small sample quantities by utilizing fast magic-angle spinning (>30 kHz) and deuteration strategies. In theory, involving 1H as one of the spins for measuring REDOR effects can greatly increase the distance measurement range, but few experiments of this type have been reported...
August 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28815532/hepatitis-c-virus-replication
#15
Tetsuro Suzuki
Viruses use synthetic mechanism and organelles of the host cells to facilitate their replication and make new viruses. Host's ATP provides necessary energy. Hepatitis C virus (HCV) is a major cause of liver disease. Like other positive-strand RNA viruses, the HCV genome is thought to be synthesized by the replication complex, which consists of viral- and host cell-derived factors, in tight association with structurally rearranged vesicle-like cytoplasmic membranes. The virus-induced remodeling of subcellular membranes, which protect the viral RNA from nucleases in the cytoplasm, promotes efficient replication of HCV genome...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814780/adaptive-simulations-towards-interactive-protein-ligand-modeling
#16
Daniel Lecina, Joan F Gilabert, Victor Guallar
Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations, we still lack a fast and accurate ab initio description of the binding mechanism in complex systems, available only for up-to-date techniques and requiring several hours or days of heavy computation...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814746/rewiring-of-the-ftsh-regulatory-network-by-a-single-nucleotide-change-in-saes-of-staphylococcus-aureus
#17
Qian Liu, Mo Hu, Won-Sik Yeo, Lei He, Tianming Li, Yuanjun Zhu, Hongwei Meng, Yanan Wang, Hyunwoo Lee, Xiaoyun Liu, Min Li, Taeok Bae
In the Gram-positive pathogen Staphylococcus aureus, the membrane-bound ATP-dependent metalloprotease FtsH plays a critical role in resistance to various stressors. However, the molecular mechanism of the FtsH functions is not known. Here, we identified core FtsH target proteins in S. aureus. In the strains Newman and USA300, the abundance of 33 proteins were altered in both strains, of which 11 were identified as core FtsH substrate protein candidates. In the strain Newman and some other S. aureus strains, the sensor histidine kinase SaeS has an L18P (T53C in saeS) substitution, which transformed the protein into an FtsH substrate...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814570/eb1-and-eb3-regulate-microtubule-minus-end-organization-and-golgi-morphology
#18
Chao Yang, Jingchao Wu, Cecilia de Heus, Ilya Grigoriev, Nalan Liv, Yao Yao, Ihor Smal, Erik Meijering, Judith Klumperman, Robert Z Qi, Anna Akhmanova
End-binding proteins (EBs) are the core components of microtubule plus end tracking protein complexes, but it is currently unknown whether they are essential for mammalian microtubule organization. Here, by using CRISPR/Cas9-mediated knockout technology, we generated stable cell lines lacking EB2 and EB3 and the C-terminal partner-binding half of EB1. These cell lines show only mild defects in cell division and microtubule polymerization. However, the length of CAMSAP2-decorated stretches at noncentrosomal microtubule minus ends in these cells is reduced, microtubules are detached from Golgi membranes, and the Golgi complex is more compact...
August 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28814506/role-of-clathrin-in-dense-core-vesicle-biogenesis
#19
Bhavani S Sahu, Paul T Manna, James R Edgar, Robin Antrobus, Sushil K Mahata, Alessandro Bartolomucci, Georg H H Borner, Margaret S Robinson
The dense-core vesicles (DCVs) of neuroendocrine cells are a rich source of bioactive molecules such as peptides, hormones, and neurotransmitters, but relatively little is known about how they are formed. Using fractionation profiling, a method that combines subcellular fractionation with mass spectrometry, we identified ∼1200 proteins in PC12 cell vesicle-enriched fractions, with DCV-associated proteins showing distinct profiles from proteins associated with other types of vesicles. To investigate the role of clathrin in DCV biogenesis, we stably transduced PC12 cells with an inducible shRNA targeting clathrin heavy chain, resulting in ∼85% protein loss...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28814505/the-molecular-architecture-of-the-yeast-spindle-pole-body-core-determined-by-bayesian-integrative-modeling
#20
Shruthi Viswanath, Massimiliano Bonomi, Seung Joong Kim, Vadim A Klenchin, Keenan C Taylor, King C Yabut, Neil T Umbreit, Heather A Van Epps, Janet Meehl, Michele H Jones, Daniel Russel, Javier A Velazquez-Muriel, Mark Winey, Ivan Rayment, Trisha N Davis, Andrej Sali, Eric G Muller
Microtubule organizing centers (MTOCs) form, anchor and stabilize the polarized network of microtubules in a cell. The central MTOC is the centrosome that duplicates during the cell cycle and during mitosis assembles a bipolar spindle to capture and segregate sister chromatids. Yet, despite their importance in cell biology, the physical structure of MTOCs is poorly understood. Here we determine the molecular architecture of the core of the yeast spindle pole body (SPB) by Bayesian integrative structure modeling based on in vivo FRET, small-angle X-ray scattering (SAXS), X-ray crystallography, electron microscopy and two-hybrid analysis...
August 16, 2017: Molecular Biology of the Cell
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