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https://www.readbyqxmd.com/read/28040513/novel-chimeric-virus-like-particles-vaccine-displaying-mers-cov-receptor-binding-domain-induce-specific-humoral-and-cellular-immune-response-in-mice
#1
Chong Wang, Xuexing Zheng, Weiwei Gai, Gary Wong, Hualei Wang, Hongli Jin, Na Feng, Yongkun Zhao, Weijiao Zhang, Nan Li, Guoxing Zhao, Junfu Li, Jinghua Yan, Yuwei Gao, Guixue Hu, Songtao Yang, Xianzhu Xia
Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP)...
December 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/28008928/cryo-electron-microscopy-structures-of-the-sars-cov-spike-glycoprotein-reveal-a-prerequisite-conformational-state-for-receptor-binding
#2
Miao Gui, Wenfei Song, Haixia Zhou, Jingwei Xu, Silian Chen, Ye Xiang, Xinquan Wang
The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in "down" positions...
December 23, 2016: Cell Research
https://www.readbyqxmd.com/read/27979965/defining-minimal-binding-regions-in-regulator-of-presynaptic-morphology-1-rpm-1-using-c-elegans-neurons-reveals-differential-signaling-complexes
#3
Scott T Baker, Brock Grill
The intracellular signaling protein RPM-1 is a conserved regulator of synapse formation and axon termination in C. elegans. RPM-1 functions in a ubiquitin ligase complex with the F-box protein FSN-1, and functions through the microtubule binding protein RAE-1. Using a structure-function approach and positive selection for transgenic C. elegans, we explored the biochemical relationship between RPM-1, FSN-1, and RAE-1. This led to the identification of two new domains in RPM-1 that are sufficient for binding to FSN-1, called FSN-1 binding domain 2 (FBD2) and FBD3...
December 15, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27965397/rem-sleep-behaviour-disorder-prodromal-and-mechanistic-insights-for-parkinson-s-disease
#4
REVIEW
Anand Tekriwal, Drew S Kern, Jean Tsai, Nuri F Ince, Jianping Wu, John A Thompson, Aviva Abosch
Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by complex motor enactment of dreams and is a potential prodromal marker of Parkinson's disease (PD). Of note, patients with PD observed during RBD episodes exhibit improved motor function, relative to baseline states during wake periods. Here, we review recent epidemiological and mechanistic findings supporting the prodromal value of RBD for PD, incorporating clinical and electrophysiological studies. Explanations for the improved motor function during RBD episodes are evaluated in light of recent publications...
December 13, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27956239/rnacompete-methodology-and-application-to-determine-sequence-preferences-of-unconventional-rna-binding-proteins
#5
Debashish Ray, Kevin C H Ha, Kate Nie, Hong Zheng, Timothy R Hughes, Quaid D Morris
RNA-binding proteins (RBPs) participate in diverse cellular processes and have important roles in human development and disease. The human genome, and that of many other eukaryotes, encodes hundreds of RBPs that contain canonical sequence-specific RNA-binding domains (RBDs) as well as numerous other unconventional RNA binding proteins (ucRBPs). ucRBPs physically associate with RNA but lack common RBDs. The degree to which these proteins bind RNA, in a sequence specific manner, is unknown. Here, we provide a detailed description of both the laboratory and data processing methods for RNAcompete, a method we have previously used to analyze the RNA binding preferences of hundreds of RBD-containing RBPs, from diverse eukaryotes...
December 10, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27936982/mers-cov-spike-protein-a-key-target-for-antivirals
#6
Lanying Du, Yang Yang, Yusen Zhou, Lu Lu, Fang Li, Shibo Jiang
The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides...
December 21, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27923426/periodic-limb-movements-during-sleep-mimicking-rem-sleep-behavior-disorder
#7
Carles Gaig, Alex Iranzo, Montserrat Pujo, Hernando Perez, Joan Santamaria
STUDY OBJECTIVE: To describe a group of patients referredbecause of abnormal sleep behaviors that were suggestive ofREM sleep behavior disorder (RBD) in whom videopolysomnographyruled out RBD and showed the reportedbehaviors associated with vigorous periodic limb movementsduring sleep (PLMS). METHODS: Clinical history and video-polysomnography reviewof patients identified during routine visits in a sleepcenter. RESULTS: Patients were fifteen men and two women with a median age of 66 (range 48-77) years...
November 28, 2016: Sleep
https://www.readbyqxmd.com/read/27923423/comparison-between-automatic-and-visual-scorings-of-rem-sleep-without-atonia-for-the-diagnosis-of-rem-sleep-behavior-disorder-in-parkinson-disease
#8
Michela Figorilli, Raffaele Ferri, Maurizio Zibetti, Patricia Beudin, Monica Puligheddu, Leonardo Lopiano, Alessandro Cicolin, Frank Durif, Ana Marques, Maria Livia Fantini
STUDY OBJECTIVES: To compare three different methods, two visual and one automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD) in Parkinson's disease (PD) patients. METHODS: Sixty-two consecutive patients with idiopathic PD underwent videopolysomnographic recording and showed more than 5 minutes of REM sleep. The electromyogram (EMG) during REM sleep was analyzed by means of two visual methods (Montréal and SINBAR) and one automatic analysis (REM Atonia Index or RAI)...
November 28, 2016: Sleep
https://www.readbyqxmd.com/read/27911340/dementia-predictors-in-parkinson-disease-a-validation-study
#9
Julius Bm Anang, Takashi Nomura, Silvia Rios Romenets, Kenji Nakashima, Jean-Francois Gagnon, Ronald B Postuma
In a prospective study, we recently discovered 8 clinical predictors of dementia in Parkinson's disease. Here, we validate these dementia predictors using two additional prospective cohorts (n = 134). After a 3.6-year follow-up, 35/134 developed dementia (7.2% per year). When confirming individual variables, 5/8 were significantly associated with dementia in the validation cohort. These included age, male sex, baseline RBD, orthostatic hypotension, and MCI. Bilateral onset, hallucinations and falls/freezing did not significantly predict dementia; however, point estimates of OR were all >1...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27905363/-sleep-disorders-in-the-early-stage-of-parkinson-s-disease-in-untreated-patients
#10
N A Amosova, I G Smolentseva, P M Guseinova, O A Maslyuk, E L Gavrilov
Disorders of sleep and wakefulness occur in about 60-98% of patients with Parkinson's disease (PD). The majority of research on the scale and nature of the disorders was performed in patients treated with antiparkinsonian drugs, and, therefore, the true picture of sleep disorders was interfering with side effects of therapy. The spectrum of these disorders in PD patients is broad and includes insomnia, parasomnia and hypersomnia. The main symptoms of insomnia are difficulty in maintaining sleep, associated with nocturia, rapid eye movement (REM) sleep behavior disorder (RBD), night cramps, akinesia and tremor...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27900364/analysis-of-intrapatient-heterogeneity-uncovers-the-microevolution-of-middle-east-respiratory-syndrome-coronavirus
#11
Donghyun Park, Hee Jae Huh, Yeon Jeong Kim, Dae-Soon Son, Hyo-Jeong Jeon, Eu-Hyun Im, Jong-Won Kim, Nam Yong Lee, Eun-Suk Kang, Cheol In Kang, Doo Ryeon Chung, Jin-Hyun Ahn, Kyong Ran Peck, Sun Shim Choi, Yae-Jean Kim, Chang-Seok Ki, Woong-Yang Park
Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non-consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899666/structures-of-human-srp72-complexes-provide-insights-into-srp-rna-remodeling-and-ribosome-interaction
#12
Matthias M M Becker, Karine Lapouge, Bernd Segnitz, Klemens Wild, Irmgard Sinning
Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899228/the-recombinant-n-terminal-domain-of-spike-proteins-is-a-potential-vaccine-against-middle-east-respiratory-syndrome-coronavirus-mers-cov-infection
#13
Lan Jiaming, Yao Yanfeng, Deng Yao, Hu Yawei, Bao Linlin, Huang Baoying, Yan Jinghua, George F Gao, Qin Chuan, Tan Wenjie
The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10μg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity)...
January 3, 2017: Vaccine
https://www.readbyqxmd.com/read/27888574/normal-heart-in-parkinson-s-disease-is-this-a-distinct-clinical-phenotype
#14
J-S Kim, H-E Park, I-S Park, Y-S Oh, D-W Ryu, I-U Song, Y-A Jung, I R Yoo, H-S Choi, P H Lee, K-S Lee
BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake...
November 26, 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/27886007/sleep-wake-profile-in-dementia-with-lewy-bodies-alzheimer-s-disease-and-normal-aging
#15
Annachiara Cagnin, Federica Fragiacomo, Giulia Camporese, Matteo Turco, Cinzia Bussè, Mario Ermani, Sara Montagnese
BACKGROUND: Alterations of the sleep-wake cycle are common features of neurodegenerative dementia. OBJECTIVES: To study differences in sleep-wake profiles in dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and healthy controls. METHODS: 30 DLB and 32 AD patients, and 33 healthy elderly participants were studied. Patients were evaluated for global cognitive impairment, extrapyramidal signs, fluctuations of attention, and behavioral disorders...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27880010/abnormal-baseline-brain-activity-in-parkinson-s-disease-with-and-without-rem-sleep-behavior-disorder-a-resting-state-functional-mri-study
#16
Dan Li, Peiyu Huang, Yufeng Zang, Yuting Lou, Zhidong Cen, Quanquan Gu, Min Xuan, Fei Xie, Zhiyuan Ouyang, Bo Wang, Minming Zhang, Wei Luo
PURPOSE: To investigate the differences in spontaneous brain activity between Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD), PD patients without RBD, and normal controls, which may shed new light on the neural mechanism of RBD. MATERIALS AND METHODS: Eighteen PD patients with RBD, 16 patients without RBD, and 19 age- and gender-matched normal controls underwent clinical assessment and functional magnetic resonance imaging (fMRI) with a 3...
November 23, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27871184/in-vitro-evaluation-of-prebiotic-properties-derived-from-rice-bran-obtained-by-debranning-technology
#17
Premsuda Saman, Kieran M Tuohy, José A Vázquez, Glenn Gibson, Severino S Pandiella
The prebiotic ability of several rice bran fractions obtained by debranning (RBD) using human microbiota was studied in anaerobic batch cultures with agitation and pH-controlled. Fraction C (3.8-5% w/w pearling) from RBD increased the number of bifidobacteria and lactobacteria compared with the positive control, raftilose P95. RBD fermentation induced changes in the short-chain fatty acid (SCFA) profile. In addition, Fraction C revealed the highest growth of positive lactobacteria than commercial control. The present work illustrates the prebiotic capacity of RBD to modulate human microbiota and highlights that fraction C could be an economical source for use in human food as well as an interesting alternative to valorise a by-product of cereal industry...
November 21, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27865780/rasins-genetically-encoded-intrabodies-of-activated-ras-proteins
#18
Mehmet Cetin, William E Evenson, Garret G Gross, Farzad Jalali-Yazdi, Daniel Krieger, Don Arnold, Terry T Takahashi, Richard W Roberts
K- and H-Ras are the most commonly mutated genes in human tumors and are critical for conferring and maintaining the oncogenic phenotype in tumors with poor prognoses. Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which use the 10th domain of human fibronectin as their scaffold, are stable inside cells and when fused with a fluorescent protein label constitutively active G12V mutant H-Ras. Primary selection of ligands against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a KD of 2...
November 16, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27855735/pareidolias-in-rem-sleep-behavior-disorder-a-possible-predictive-marker-of-lewy-body-diseases
#19
Taeko Sasai-Sakuma, Yoshiyuki Nishio, Kayoko Yokoi, Etsuro Mori, Yuichi Inoue
STUDY OBJECTIVES: To investigate conditions and clinical significance of pareidolias in patients with idiopathic REM sleep behavior disorder (iRBD). METHODS: This cross-sectional study examined 202 patients with idiopathic rapid eye movement sleep behavior disorder (66.8±8.0 yr, 58 female) and 46 healthy control subjects (64.7±5.8 yr, 14 female). They underwent the Pareidolia test, a newly developed instrument for evoking pareidolias, video-polysomnography, olfactory tests, and Addenbrooke's cognitive examination - revised...
October 28, 2016: Sleep
https://www.readbyqxmd.com/read/27855295/establishment-of-a-bleeding-score-as-a-diagnostic-tool-for-patients-with-rare-bleeding-disorders
#20
Roberta Palla, Simona M Siboni, Marzia Menegatti, Khaled M Musallam, Flora Peyvandi
INTRODUCTION: Bleeding manifestations among patients with rare bleeding disorders (RBDs) vary significantly between disorders and patients, even when affected with the same disorder. In response to the challenge represented by the clinical assessment of the presence and severity of bleeding symptoms, a number of bleeding score systems (BSSs) or bleeding assessment tools (BATs) were developed. The majority of these were specifically developed for patients with more common bleeding disorders than RBDs...
December 2016: Thrombosis Research
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