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1.
ISA Trans ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33627257

RESUMO

Safety instrumented systems often employ redundancy to enhance the ability to detect and respond to hazardous events. The use of redundancy increases the fault tolerance to single failure but remains vulnerable in case of dependent failures, including common cause failures and cascading failures. Reliability analysis of safety instrumented systems therefore involves the impact of dependent failures. The used approaches have primarily focused on common cause failures. In this paper, it is argued the need to consider the efforts of cascading failures that are caused by functional dependencies, hazardous events, and shared resources. A recursive aggregation-based approach is proposed for performance analyzing of K-out-of-N safety instrumented systems with consideration of cascading failures. General approximation formulas are developed for estimating the average probability of failures on demand of different configurations of safety instrumented systems. These formulas are compared with those for common cause failures. Then a case of fire water pump is studied to illustrate the effects of cascading failures on safety instrumented systems.

2.
Foods ; 9(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143312

RESUMO

Salmon is a highly perishable food due to temperature, pH, odor, and texture changes during cold storage. Intelligent monitoring and spoilage rapid detection are effective approaches to improve freshness. The aim of this work was an evaluation of IoT-enabled monitoring system (IoTMS) and electronic nose spoilage detection for quality parameters changes and freshness under cold storage conditions. The salmon samples were analyzed and divided into three groups in an incubator set at 0 °C, 4 °C, and 6 °C. The quality parameters, i.e., texture, color, sensory, and pH changes, were measured and evaluated at different temperatures after 0, 3, 6, 9, 12, and 14 days of cold storage. The principal component analysis (PCA) algorithm can be used to cluster electronic nose information. Furthermore, a Convolutional Neural Networks and Support Vector Machine (CNN-SVM) based algorithm is used to cluster the freshness level of salmon samples stored in a specific storage condition. In the tested samples, the results show that the training dataset of freshness is about 95.6%, and the accuracy rate of the test dataset is 93.8%. For the training dataset of corruption, the accuracy rate is about 91.4%, and the accuracy rate of the test dataset is 90.5%. The overall accuracy rate is more than 90%. This work could help to reduce quality loss during salmon cold storage.

3.
J Am Chem Soc ; 140(9): 3423-3433, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29457449

RESUMO

Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media. The ability of SCPNs to act as catalysts in biological media was first assessed by investigating their potential for reactive oxygen species generation. With porphyrins covalently attached to the SCPNs, singlet oxygen was generated upon irradiation with light, inducing spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based SCPNs were prepared and these catalysts were screened in vitro and studied in cellular environments for the carbamate cleavage reaction of rhodamine-based substrates. This is a model reaction for the uncaging of bioactive compounds such as cytotoxic drugs for catalysis-based cancer therapy. We observed that the rate of the deprotection depends on both the organometallic catalysts and the nature of the protective group. The rate reduces from in vitro to the biological environment, indicating a strong influence of biomolecules on catalyst performance. The Cu(I)-based SCPNs in combination with the dimethylpropargyloxycarbonyl protective group showed the best performances both in vitro and in biological environment, making this group promising in biomedical applications.


Assuntos
Nanopartículas/química , Polímeros/química , Porfirinas/química , Oxigênio Singlete/química , Catálise , Morte Celular , Cobre/química , Células HeLa , Humanos , Luz , Nanopartículas/ultraestrutura , Paládio/química , Tamanho da Partícula
4.
Front Pharmacol ; 9: 28, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441018

RESUMO

Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder with the highest incidence in the world. Dysfunction of the blood-brain barrier (BBB) may be responsible for the pathogenesis and pathology of AD for abnormally transporting amyloid-ß (Aß, the main component of the senile plaques) from the sera into the central nervous system. Aß peptides induce apoptosis in human brain microvascular endothelial cells (hBMECs), the main component of BBB. Apoptosis in neuronal cells plays a critical role in the pathogenesis of AD. Asiaticoside, a natural glycoside extracted from Centella asiatica (L.) Urban, has an anti-apoptotic effect on hBMECs but the molecule mechanism remains unclear. Therefore, we investigate the protective effect of asiaticoside on Aß1-42-induced cytotoxicity and apoptosis as well as associated mechanism in hBMECs with commonly used in vitro methods for clinical development of asiaticoside as a novel anti-AD agent. In the present study, we investigated the effects of asiaticoside on cytotoxicity by Cell Counting Kit-8 assay, mitochondrial membrane potential by JC-1 fluorescence analysis, anti-apoptosis by Hoechst 33258 staining and Annexin V-FITC (fluorescein isothiocyanate) and propidium iodide (PI) analyses, the expressions of TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA) and TLR4, MyD88, TRAF6, p-NF-κB p65, and total NF-κB p65 by Western blotting, and nuclear translocation of NF-κB p65 by immunofluorescence analysis in hBMECs. The results showed that pretreatment of asiaticoside (25, 50, and 100 µM) for 12 h significantly attenuated cell growth inhibition and apoptosis, and restored declined mitochondrial membrane potential induced by Aß1-42 (50 µM) in hBMECs. Asiaticoside also significantly downregulated the elevated expressions of TNF-α, IL-6, TLR4, MyD88, TRAF6, and p-NF-κB p65, as well as inhibited NF-κB p65 translocation from cytoplasm to nucleus induced by Aß1-42 in hBMECs in a concentration-dependent manner. The possible underlying molecular mechanism of asiaticoside may be through inhibiting the TLR4/NF-κB signaling pathway. Therefore, asiaticoside may be developed as a novel agent for the prevention and/or treatment of AD clinically.

5.
Macromolecules ; 50(21): 8562-8569, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29151619

RESUMO

A family of amphiphilic, heterograft copolymers containing hydrophilic, hydrophobic, and supramolecular units based on Jeffamine M-1000, dodecylamine, and benzene-1,3,5-tricarboxamide (BTA) motifs, respectively, was prepared via a postfunctionalization approach. The folding of the copolymers in water into nanometer-sized particles was analyzed by a combination of dynamic and static light scattering, circular dichroism spectroscopy, and small-angle neutron scattering. The sample preparation protocol was crucial for obtaining reproducible and consistent results, showing that only full control over the structure and pathway complexity will afford the desired folded structure, a phenomenon similar to protein folding. The results revealed that relatively small changes in the polymer's graft composition strongly affected the intra- versus intermolecular assembly processes. Depending on the amount of the hydrophobic grafts based on either dodecyl or BTA groups, pronounced behavioral differences were observed for copolymers that comprise similar degrees of hydrophobic content. A high number of BTA grafts (>10%) resulted in the formation of multichain aggregates comprising around six polymer chains. In contrast, for copolymers comprising up to 10% BTA grafts the folding results in nanoparticles that adopt open, sparse conformations and comprise one to two polymer chains. Interestingly, predominantly single-chain polymeric nanoparticles were formed when the copolymer comprised only Jeffamine or Jeffamine and dodecyl grafts. In addition, replacing part of the BTA grafts by hydrophobic dodecyl grafts while keeping the hydrophobic content constant promoted single-chain folding and resulted in the formation of a compact, globular nanoparticle with a more structured interior. Thus, the intra- and intermolecular self-assembly pathways can be directed by carefully tuning the polymer's hydrophilic-hydrophobic balance in combination with the number of supramolecular grafts.

6.
Mol Ther ; 25(8): 1900-1916, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28527723

RESUMO

Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models. Chemoresistant A549 lung cancer cells that display constitutive dominant hyperactivation of Nrf2 signaling are particularly vulnerable to VSVΔ51 oncolysis. Mechanistically, enhanced Nrf2 signaling stimulated viral replication in cancer cells and disrupted the type I IFN response via increased autophagy. This study reveals a previously unappreciated role for Nrf2 in the regulation of autophagy and the innate antiviral response that complements the therapeutic potential of VSV-directed oncolysis against multiple types of OV-resistant or chemoresistant cancer.


Assuntos
Autofagia , Fator 2 Relacionado a NF-E2/metabolismo , Vírus Oncolíticos/fisiologia , Transdução de Sinais , Estomatite Vesicular/metabolismo , Estomatite Vesicular/virologia , Vírus da Estomatite Vesicular Indiana/fisiologia , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular , Terapia Combinada , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Isotiocianatos/farmacologia , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Neoplasias/metabolismo , Neoplasias/mortalidade , Neoplasias/patologia , Neoplasias/terapia , Terapia Viral Oncolítica , Deleção de Sequência , Transdução de Sinais/efeitos dos fármacos , Estomatite Vesicular/imunologia , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacos , Proteínas da Matriz Viral/genética , Replicação Viral/efeitos dos fármacos
7.
Inflamm Cell Signal ; 4(1): e1491, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28191486

RESUMO

The innate immune sensing of pathogens is important for host to mount defensive responses. STING has emerged in recent years as a critical signaling adaptor in the immune response to cytosolic DNA and RNA derived from pathogens. Liu et al. (2016) demonstrate that the RIG-I-dependent RNA sensing signaling induces STING expression via a TNF-α and IFN-α synergy. The up-regulation of STING is vital for 5'pppRNA restriction of HSV, a DNA virus that infects humans and causes herpes, in vitro and in vivo. This study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING.

8.
Mol Cell Biol ; 37(6)2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27956705

RESUMO

Transcription of type I interferon genes during RNA virus infection requires signal communication between several pattern recognition receptor (PRR)-adaptor complexes located at distinct subcellular membranous compartments and a central cytoplasmic TBK1-interferon regulatory factor 3 (IRF3) kinase-transcription factor module. However, how the cell integrates signal transduction through spatially distinct modules of antiviral signaling pathways is less defined. RIG-I is a major cytosolic PRR involved in the control of several RNA viruses. Here we identify ArfGAP domain-containing protein 2 (ADAP2) as a key novel scaffolding protein that integrates different modules of the RIG-I pathway, located at distinct subcellular locations, and mediates cellular antiviral type I interferon production. ADAP2 served to bridge the mitochondrial membrane-bound upstream RIG-I adaptor MAVS and the downstream cytosolic complex of NEMO (regulatory subunit of TBK1), TBK1, and IRF3, leading to IRF3 phosphorylation. Furthermore, independently, ADAP2 also functioned as a major orchestrator of the interaction of TBK1 with NEMO and IRF3. Mutational and in vitro cell-free reconstituted RIG-I signaling assay-based analyses identified that the ArfGAP domain of ADAP2 mediates the interferon response. TRAF3 acted as a trigger for ADAP2 to recruit RIG-I pathway component proteins into a single macromolecular complex. This study provides important novel insights into the assembly and integration of different modules of antiviral signaling cascades.


Assuntos
Proteína DEAD-box 58/metabolismo , Proteínas Ativadoras de GTPase/química , Proteínas Ativadoras de GTPase/metabolismo , Interferon Tipo I/biossíntese , Transdução de Sinais , Sistema Livre de Células , Proteínas Ativadoras de GTPase/genética , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/genética , Modelos Biológicos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos , Receptores de Reconhecimento de Padrão/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Frações Subcelulares/metabolismo , Transcrição Genética/efeitos dos fármacos , Vesiculovirus/fisiologia
9.
J Virol ; 90(20): 9406-19, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27512060

RESUMO

UNLABELLED: STING has emerged in recent years as a key player in orchestrating innate immune responses to cytosolic DNA and RNA derived from pathogens. However, the regulation of STING still remains poorly defined. In the present study, we investigated the mechanism of the regulation of STING expression in relation to the RIG-I pathway. Our data show that signaling through RIG-I induces STING expression at both the transcriptional and protein levels in various cell types. STING induction by the RIG-I agonist 5'triphosphorylated RNA (5'pppRNA) was recognized to be a delayed event resulting from an autocrine/paracrine mechanism. Indeed, cotreatment with tumor necrosis factor alpha and type I/II interferon was found to have a synergistic effect on the regulation of STING expression and could be potently decreased by impairing NF-κB and/or STAT1/2 signaling. STING induction significantly contributed to sustainment of the immune signaling cascade following 5'pppRNA treatment. Physiologically, this cross talk between the RNA- and DNA-sensing pathways allowed 5'pppRNA to efficiently block infection by herpes simplex virus 1 (HSV-1) both in vitro and in vivo in a STING-dependent fashion. These observations demonstrate that STING induction by RIG-I signaling through the NF-κB and STAT1/2 cascades is essential for RIG-I agonist-mediated HSV-1 restriction. IMPORTANCE: The innate immune system represents the first line of defense against invading pathogens. The dysregulation of this system can result in failure to combat pathogens, inflammation, and autoimmune diseases. Thus, precise regulation at each level of the innate immune system is crucial. Recently, a number of studies have established STING to be a central molecule in the innate immune response to cytosolic DNA and RNA derived from pathogens. Here, we describe the regulation of STING via RIG-I-mediated innate immune sensing. We found that STING is synergistically induced via proinflammatory and antiviral cytokine cascades. In addition, we show that in vivo protection against herpes simplex virus 1 (HSV-1) by a RIG-I agonist required STING. Our study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING.


Assuntos
Proteína DEAD-box 58/metabolismo , Herpes Simples/metabolismo , Herpesvirus Humano 1/metabolismo , Proteínas de Membrana/metabolismo , Regulação para Cima/fisiologia , Células A549 , Linhagem Celular , Linhagem Celular Tumoral , Citocinas/metabolismo , Humanos , Imunidade Inata/fisiologia , Interferon Tipo I/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais/fisiologia , Ativação Transcricional/fisiologia
10.
Front Immunol ; 7: 662, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28096803

RESUMO

Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus-host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling.

11.
J Am Chem Soc ; 137(40): 13096-105, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26388188

RESUMO

Single-chain polymeric nanoparticles (SCPNs) are intriguing systems for multiple applications. In order to arrive at a controlled, but random, positioning of the different side groups to the polymer backbone, alternative synthetic routes have to be developed. Here, a general postpolymerization modification strategy of poly(pentafluorophenyl acrylate) (pPFPA) is presented as a versatile method to rapidly access functional SCPNs. We first show that the sequential addition of a benzene-1,3,5-tricarboxamide-based amine, acting as the supramolecular recognition motif, and water-soluble polyetheramine (Jeffamine) to pPFPA affords random copolymers that fold in water into SCPNs. The scope of the modular platform is illustrated by preparing two types of functional SCPNs. First, we prepared SCPNs designed for bio-orthogonal catalysis by attaching pendant mono(benzimidazoylmethyl)-bis(pyridylmethyl) (Bimpy), phenanthroline (Phen), or 2,2'-bipyridine (BiPy), ligands capable of binding either Cu(I) or Pd(II). The Bimpy- and Phen-containing SCPNs ligated to Cu(I) significantly accelerate azide-alkyne cycloaddition reactions while Bipy-containing SCPNs ligated to Pd(II) efficiently catalyze depropargylation reactions. In all cases, reactions proceeded efficiently in phosphate buffer at a physiological pH and at low substrate concentrations. Next, the potential of SCPNs for photodynamic therapy was evaluated. Introducing porphyrins in SCPNs leads to novel photosensitizers that can produce singlet oxygen ((1)O2) upon photoirradiation. Additionally, by attaching both porphyrins and prodrug models, attached via (1)O2-cleavable amino-acrylate linker, to the SCPNs, we show that irradiation of the SCPNs results in a cascade reaction of (1)O2 generation followed by cleavage of the amino-acrylate linkers, releasing the drug model. The modular synthesis strategy reported here provides rapid and controlled access to SCPNs with tunable amounts of active units that fulfill different functions.

12.
Angew Chem Int Ed Engl ; 53(21): 5351-5, 2014 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-24711345

RESUMO

A new method in which supramolecular polymerization is promoted and controlled through self-sorting is reported. The bifunctional monomer containing p-phenylene and naphthalene moieties was prepared. Supramolecular polymerization is promoted by selective recognition between the p-phenylene group and cucurbit[7]uril (CB[7]), and 2:1 complexation of the naphthalene groups with cucurbit[8]uril (CB[8]). The process can be controlled by tuning the CB[7] content. This development will enrich the field of supramolecular polymers with important advances towards the realization of molecular-weight and structural control.

13.
Langmuir ; 29(42): 12909-14, 2013 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-23927076

RESUMO

The host-guest chemistry of cucurbiturils and the photochemistry of azastilbene derivatives are combined for the rationally adjusting multicolor emissions through forming different host-guest complexes and their corresponding photochemical products. Cucurbit[8]uril (CB[8]) can bind with azastilbene derivatives to form supramolecular polymers emitting orange light. The supramolecular polymers further facilitate the [2 + 2] cycloaddition of C═C bonds in azastilbenes by UV irradiation, emitting blue light. Different from CB[8], cucurbit[7]uril (CB[7]) encapsulates azastilbene derivatives to form a dumbbell-shaped host-guest complex, emitting dark-purple light. This dumbbell-shaped host-guest complex undergoes cis-isomerization after UV irradiation, thus emitting green light. Therefore, this strategy is promising for fabricating advanced stimuli-responsive fluorescent materials.

15.
Chem Commun (Camb) ; 49(51): 5766-8, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23689560

RESUMO

Linear supramolecular polymers were obtained in aqueous solution by employing cucurbit[8]uril-based host-guest interaction as the driving force. Water-soluble monomers were prepared through direct metal-coordination. The rigid and bulky terpyridine-Fe linker can effectively enhance the monomer's solubility and suppress its cyclization, thereby promoting supramolecular polymerization.

16.
Chem Asian J ; 8(8): 1626-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23589513

RESUMO

Supramolecular polymers, whose building blocks are noncovalently connected, have attracted much attention over the last few decades. The noncovalent nature of these polymeric systems endows them with great potential for applications in the preparation of dynamic materials. Cucurbituril (CB)-based host-guest systems, which have strong binding affinity and good selectivity, have received extensive recent attention. Among the CB family, is unique for its ability to bind two guests in its cavity and form strong ternary complexes. Such -based host-guest systems have been widely used in the construction of supramolecular architechtures. In this Focus Review, following a brief description of the host-guest interactions in -based systems, we summarize the current state of play in the fabrication of -based supramolecular polymers, which mainly include small-molecule-based supramolecular polymers and polymer-based supramolecular polymers, as a good example of the marriage between the supramolecular chemistry of cucurbiturils and polymer science.

17.
Chem Commun (Camb) ; 49(37): 3905-7, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23549089

RESUMO

Cucurbit[7]uril (CB[7]) as a "protective agent" can effectively inhibit the [4+4] photochemical reaction of 1,1'-(butane-1,4-diyl)bis(2-aminopyridine)bromide (DPAD) by host-guest interaction between CB[7] and DPAD. In addition, the host-guest complex DPAD-CB[7] as a supramolecular sensor can detect the concentration of 1-adamantanamine with good sensitivity and selectivity because of the guest competitive complexation.

18.
Chemistry ; 18(47): 14968-73, 2012 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-23112102

RESUMO

Stable multilayer films with cucurbit[8]uril have been fabricated on the basis of the alternating layer-by-layer assembly of a novel side-chain pseudopolyrotaxane and a photoreactive polyanion. The as-prepared multilayer films exhibit good properties as surface-imprinted multilayers, because cucurbit[8]uril molecules that are locked inside the multilayers can act as nanocontainers with specific binding to certain guest molecules, and the loading and release of the guest is redox-controllable and reversible.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Ciclodextrinas/química , Imidazóis/química , Nanoestruturas/química , Poloxâmero/química , Rotaxanos/química , Modelos Moleculares , Estrutura Molecular , Oxirredução , Polímeros/química , Propriedades de Superfície
19.
Chemistry ; 18(49): 15650-4, 2012 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-23070871

RESUMO

We present the construction of long-chain water-soluble supramolecular polymers at low monomer concentrations. Naphthalene-based host-enhanced π-π interactions, which possess high binding constants, were used as the driving force of supramolecular polymerization. A monomer, DNDAB, with a rigid, bulky 1,4-diazabicyclo[2.2.2]octane-1,4-diium linker was designed. The design of the monomer structure strongly influenced the efficiency of the supramolecular polymerization. The rigid, bulky linker in DNDAB effectively eliminates cyclization, promoting the formation of long-chain supramolecular polymers at low monomer concentrations. In contrast, a reference monomer containing a flexible linker (DNPDN) only forms oligomers owing to cyclization.

20.
J Virol ; 86(18): 9899-910, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22761376

RESUMO

The distal portion of rotavirus (RV) VP4 spike protein (VP8*) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8* of some animal RVs engage sialic acid, human RVs often attach to and enter cells in a sialic acid-independent manner. A recent study demonstrated that the major human RVs (P[4], P[6], and P[8]) recognize human histo-blood group antigens (HBGAs). In this study, we performed a phylogenetic analysis of RVs and showed further variations of RV interaction with HBGAs. On the basis of the VP8* sequences, RVs are grouped into five P genogroups (P[I] to P[V]), of which P[I], P[IV], and P[V] mainly infect animals, P[II] infects humans, and P[III] infects both animals and humans. The sialic acid-dependent RVs (P[1], P[2], P[3], and P[7]) form a subcluster within P[I], while all three major P genotypes of human RVs (P[4], P[6], and P[8]) are clustered in P[II]. We then characterized three human RVs (P[9], P[14], and P[25]) in P[III] and observed a new pattern of binding to the type A antigen which is distinct from that of the P[II] RVs. The binding was demonstrated by hemagglutination and saliva binding assay using recombinant VP8* and native RVs. Homology modeling and mutagenesis study showed that the locations of the carbohydrate binding interfaces are shared with the sialic acid-dependent RVs, although different amino acids are involved. The P[III] VP8* proteins also bind the A antigens of the porcine and bovine mucins, suggesting the A antigen as a possible factor for cross-species transmission of RVs. Our study suggests that HBGAs play an important role in RV infection and evolution.


Assuntos
Antígenos de Grupos Sanguíneos/fisiologia , Proteínas de Ligação a RNA/fisiologia , Rotavirus/patogenicidade , Proteínas não Estruturais Virais/fisiologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sítios de Ligação , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/fisiologia , Bovinos , Especificidade de Hospedeiro/fisiologia , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mucinas/metabolismo , Mutagênese Sítio-Dirigida , Filogenia , Domínios e Motivos de Interação entre Proteínas , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Rotavirus/classificação , Rotavirus/genética , Rotavirus/fisiologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/transmissão , Infecções por Rotavirus/virologia , Ácidos Siálicos/metabolismo , Suínos , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
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