Journal articles on the topic 'AMF interaction specificity'
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1
Tao, Leiling, Camden D. Gowler, Aamina Ahmad, Mark D. Hunter, and Jacobus C. de Roode. "Disease ecology across soil boundaries: effects of below-ground fungi on above-ground host–parasite interactions." Proceedings of the Royal Society B: Biological Sciences 282, no. 1817 (October 22, 2015): 20151993. http://dx.doi.org/10.1098/rspb.2015.1993.
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Host–parasite interactions are subject to strong trait-mediated indirect effects from other species. However, it remains unexplored whether such indirect effects may occur across soil boundaries and connect spatially isolated organisms. Here, we demonstrate that, by changing plant (milkweed Asclepias sp.) traits, arbuscular mycorrhizal fungi (AMF) significantly affect interactions between a herbivore (the monarch butterfly Danaus plexippus ) and its protozoan parasite ( Ophryocystis elektroscirrha ), which represents an interaction across four biological kingdoms. In our experiment, AMF affected parasite virulence, host resistance and host tolerance to the parasite. These effects were dependent on both the density of AMF and the identity of milkweed species: AMF indirectly increased disease in monarchs reared on some species, while alleviating disease in monarchs reared on other species. The species-specificity was driven largely by the effects of AMF on both plant primary (phosphorus) and secondary (cardenolides; toxins in milkweeds) traits. Our study demonstrates that trait-mediated indirect effects in disease ecology are extensive, such that below-ground interactions between AMF and plant roots can alter host–parasite interactions above ground. In general, soil biota may play an underappreciated role in the ecology of many terrestrial host–parasite systems.
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Selim, Samy, Walid Abuelsoud, Salam S. Alsharari, Bassam F. Alowaiesh, Mohammad M. Al-Sanea, Soad Al Jaouni, Mahmoud M. Y. Madany, and Hamada AbdElgawad. "Improved Mineral Acquisition, Sugars Metabolism and Redox Status after Mycorrhizal Inoculation Are the Basis for Tolerance to Vanadium Stress in C3 and C4 Grasses." Journal of Fungi 7, no. 11 (October 27, 2021): 915. http://dx.doi.org/10.3390/jof7110915.
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Vanadium (V) can be beneficial or toxic to plant growth and the interaction between arbuscular mycorrhizal fungi (AMF) and V stress was rarely investigated at physiological and biochemical levels of plant groups (C3 and C4) and organs (roots and shoots). We tested the potential of AMF to alleviate the negative effects of V (350 mg V/Kg soil) on shoots and roots of rye and sorghum. Relative to sorghum (C4), rye (C3) showed higher levels of V and lower levels of key elements under V stress conditions. V inhibited growth, photosynthesis, and induced photorespiration (increased HDR & GO activities) and oxidative damage in both plants. AMF colonization reduced V stress by differently mitigating the oxidative stress in rye and sorghum. This mitigation was accompanied with increases in acid and alkaline phosphatase activities in plant roots and increased organic acids and polyphenols exudation into the soil, thus reduced V accumulation (29% and 58% in rye and sorghum shoot, respectively) and improved absorption of mineral nutrients including Ca, Mg and P. AMF colonization improved photosynthesis and increased the sugar accumulation and metabolism. Sugars also acted as a supplier of C skeletons for producing of antioxidants metabolite such as ascorbate. At the antioxidant level, rye was more responsive to the mitigating impact of AMF. Higher antioxidants and detoxification defence system (MTC, GST, phenolics, tocopherols and activities of CAT, SOD and POX) was recorded for rye, while sorghum (C4) improved its GR activity. The C3/C4-specificity was supported by principal component analysis. Together, this study provided both fundamental and applied insights into practical strategies to mitigate the phytotoxicity hazards of V in C3 and C4 grasses. Moreover, our results emphasize the importance of AMF as an environment-friendly factor to alleviate stress effects on plants and to improve growth and yield of unstressed plants.
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Nag, Kakon, Akira Kato, Tsutomu Nakada, Kazuyuki Hoshijima, Abinash Chandra Mistry, Yoshio Takei, and Shigehisa Hirose. "Molecular and functional characterization of adrenomedullin receptors in pufferfish." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290, no. 2 (February 2006): R467—R478. http://dx.doi.org/10.1152/ajpregu.00507.2005.
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The receptors for the calcitonin gene-related peptide (CGRP)/adrenomedullin (AM) family peptides were characterized in the mefugu Takifugu obscurus, a euryhaline fugu species very close to Takifugu rubripes, which has as many as five adrenomedullin genes (AM1–5). CGRP and AM share a G protein-coupled core receptor called calcitonin receptor-like receptor (CLR), and the specificity of the CLR is determined by the interaction with receptor activity-modifying proteins (RAMPs). Through database mining, three CLRs (CLR1–3) and five RAMPs (RAMP1–5) were identified, and all of them were cloned by RT-PCR and characterized by functional expression in COS7 cells in every possible combination of CLR-RAMP. The following combinations generated cAMP in response to physiological concentrations of CGRP, AM1 (an ortholog of mammalian AM), AM2, and AM5: CLR1-RAMP1/4 (CGRP), CLR1-RAMP2/3/5 (AM1), CLR2-RAMP2 (AM1), CLR1-RAMP3 (AM2), and CLR1-RAMP3 (AM5). Their expressions were found by Northern blot analysis to be tissue specific and salinity dependent. For example, CLR1-RAMP5 and CLR1-RAMP2 are expressed specifically in the gill and kidney, respectively, suggesting their involvement in osmoregulation. Furthermore, relatively high levels of CLRs and RAMPs were found in the spleen and ovary, suggesting roles in the immune and female reproductive systems. Immunohistochemistry revealed that AM receptors of the following types are expressed in the locations, indicated in brackets, of the mefugu gill and kidney: CLR1-RAMP5 (interlamellar vessels), CLR2-RAMP2 (pillar cells), and CLR1-RAMP2 (apical side of renal proximal tubule cells).
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Waar, Karola, Henny C. van der Mei, Hermie J. M. Harmsen, Joop de Vries, Jelly Atema-Smit, John E. Degener, and Henk J. Busscher. "Atomic force microscopy study on specificity and non-specificity of interaction forces between Enterococcus faecalis cells with and without aggregation substance." Microbiology 151, no. 7 (July 1, 2005): 2459–64. http://dx.doi.org/10.1099/mic.0.27877-0.
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Enterococcus faecalis is one of the leading causes of hospital-acquired infections, and indwelling medical devices are especially prone to infection. E. faecalis expressing aggregation substance (Agg) adheres to biomaterial surfaces by means of positive cooperativity, i.e. the ability of one adhering organism to stimulate adhesion of other organisms in its immediate vicinity. In this study, atomic force microscopy (AFM) was used to measure the specificity and non-specificity of interaction forces between E. faecalis cells with and without Agg. Bacteria were attached to a substratum surface and a tip-less cantilever. Two E. faecalis strains expressing different forms of Agg showed nearly twofold higher interaction forces between bacterial cells than a strain lacking Agg [adhesive force (F adh), −1·3 nN]. The strong interaction forces between the strains with Agg were reduced after adsorption of antibodies against Agg from −2·6 and −2·3 nN to −1·2 and −1·3 nN, respectively. This suggests that the non-specific interaction force between the enterococci amounts to approximately 1·2 nN, while the specific force component is only twofold stronger. Comparison of the results of the AFM interaction forces with the positive cooperativity after adhesion to a biomaterial in a parallel-plate flow chamber showed that in the absence of strong interaction forces between the cells, positive cooperativity was also absent. In conclusion, this is believed to be the first time that the influence of specific antibodies on interaction forces between E. faecalis cells has been demonstrated by AFM, thereby experimentally distinguishing between specific and non-specific force components.
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Guo, Xin, Zhen Wang, Jing Zhang, Ping Wang, Yaoming Li, and Baoming Ji. "Host-Specific Effects of Arbuscular Mycorrhizal Fungi on Two Caragana Species in Desert Grassland." Journal of Fungi 7, no. 12 (December 15, 2021): 1077. http://dx.doi.org/10.3390/jof7121077.
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Arbuscular mycorrhizal fungi (AMF), which form symbioses with most land plants, could benefit their hosts and potentially play important roles in revegetation of degraded lands. However, their application in revegetation of desert grasslands still faces challenges and uncertainties due to the unclear specificity of AMF-plant interactions. Here, Caragana korshinskii and Caragana microphylla were inoculated with either conspecific (home) or heterospecific (away) AM fungal communities from the rhizosphere of three common plant species (C. korshinskii, C. microphylla and Hedysarum laeve) in Kubuqi Desert, China. AMF communities of the inocula and their home and away effects on growth and nutrition status of two Caragana species were examined. Results showed that AMF communities of the three inocula from C. korshinskii, H. laeve and C. microphylla were significantly different, and were characterized by high abundance of Diversispora, Archaeospora, and Glomus, respectively. The shoot biomass, photosynthetic rate, foliar N and P contents of C. korshinskii only significantly increased under home AMF inoculation by 167.10%, 73.55%, 9.24%, and 23.87%, respectively. However, no significant effects of AMF on C. microphylla growth were found, regardless of home or away AMF. Positive correlations between C. korshinskii biomass and the abundance of AMF genus Diversispora were found. Our study showed strong home advantage of using native AMF community to enhance C. korshinskii growth in the desert and presented a potentially efficient way to use native AMF in restoration practices.
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Cuy-Chaparro, Laura, Michel David Bohórquez, Gabriela Arévalo-Pinzón, Jeimmy Johana Castañeda-Ramírez, Carlos Fernando Suárez, Laura Pabón, Diego Ordóñez, et al. "Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding." International Journal of Molecular Sciences 22, no. 2 (January 13, 2021): 714. http://dx.doi.org/10.3390/ijms22020714.
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Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B- and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (100YMQKFDIPRNHGSGIYVDLG119 and 120GYESVGSKSYRMPVGKCPVV139) and DII (302CPMHPVRDAIFGKWSGGSCV321)-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B- and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.
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Ratner, Buddy D., Reto Luginbühll, Rene Overney, Michael Garrison, and Thomas Boland. "Recognition, Specificity, Scanning Probe Microscopy and Biomaterials." Microscopy and Microanalysis 7, S2 (August 2001): 130–31. http://dx.doi.org/10.1017/s1431927600026726.
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Although scanning probe microscopy (SPM) can generate images of surface topography, this class of techniques is exceptionally valuable in its ability to provide quantitative and chemically specific information about biomaterial surfaces with high spatial definition. Since engineered biomaterials are designed to deliver chemically defined information, often arrayed in specific geometries, tools that can characterize such materials are needed.A few years ago, we demonstrated how the atomic force microscope (AFM) could precisely distinguish between each of the four nucleotide bases that comprise DNA, measure the nucleotide-nucleotide force of interaction and spatially localize that information on a surface (1). in particular, we found that the nucleotide bases could self-assemble on gold. The assembly process was imaged using scanning tunneling microscopy (STM) and this led to an understanding of the structure of the assembled film. The assembled film structure was further characterized using electron spectroscopy for chemical analysis (ESCA) and secondary ion mass spectrometry (SIMS).
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Dang, Ying, Xiaojun Wang, Tao Zhou, Ian A. York, and Yong-Hui Zheng. "Identification of a Novel WxSLVK Motif in the N Terminus of Human Immunodeficiency Virus and Simian Immunodeficiency Virus Vif That Is Critical for APOBEC3G and APOBEC3F Neutralization." Journal of Virology 83, no. 17 (June 17, 2009): 8544–52. http://dx.doi.org/10.1128/jvi.00651-09.
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ABSTRACT The function of lentiviral Vif proteins is to neutralize the host antiviral cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F). Vif bridges a cullin 5-based E3 ubiquitin ligase with A3G and A3F and mediates their degradation by proteasomes. Recent studies have found that Vif uses different domains to bind to A3G and A3F. A 14DRMR17 domain binds to A3F, 40YRHHY44 binds to A3G, and 69YxxL72 binds to both A3G and A3F. Here, we report another functional domain of Vif. Previously, we demonstrated that human immunodeficiency virus type 1 (HIV-1) Vif failed to mediate A3G proteasomal degradation when all 16 lysines were mutated to arginines. Here, we show that K26, and to a lesser extent K22, is critical for A3G neutralization. K22 and K26 are part of a conserved 21WxSLVK26 (x represents N, K, or H) motif that is found in most primate lentiviruses and that shows species-specific variation. Both K22 and K26 in this motif regulated Vif specificity only for A3G, whereas the SLV residues regulated Vif specificity for both A3F and A3G. Interestingly, SLV and K26 in HIV-1 Vif did not directly mediate Vif interaction with either A3G or A3F. Previously, other groups have reported an important role for W21 in A3F and A3G neutralization. Thus, 21WxSLVK26 is a novel functional domain that regulates Vif activity toward both A3F and A3G and is a potential drug target to inhibit Vif activity and block HIV-1 replication.
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Sengchaleun, Viengsamay, Hina Hakim, Sengchanh Kounnavong, and Daniel Reinharz. "Analysis of the Relevance of the Advocacy Coalition Framework to Analyze Public Policies in Non-Pluralist Countries." Social Sciences 11, no. 12 (November 28, 2022): 552. http://dx.doi.org/10.3390/socsci11120552.
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The Advocacy Coalition Framework (ACF) is a theoretical approach developed for the study of the emergence of public policies in pluralist countries. Little is known about the relevance of the framework for the study of policies in non-pluralist countries (NPCs). A review of the literature was conducted on the use of ACF in studies performed in NPCs. Nineteen documents were identified. They were based on studies conducted in China, Laos, and Vietnam. The results show that the ACF is a powerful theoretical approach for highlighting the dynamics of interactions between coalitions that exist in NPCs, as in pluralist countries, and for highlighting their specificity. ACF is a relevant tool for the study of the determinants of the emergence of public policies in NPCs.
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Zhou, Jie, Yuan Lu Cui, and Yun Qi. "A Preliminary Study of Crosslinked Alginate-Chitosan Microspheres for Delivery System." Advanced Materials Research 887-888 (February 2014): 520–23. http://dx.doi.org/10.4028/www.scientific.net/amr.887-888.520.
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Glutaraldehyde cross-linked chitosan coated-alginate microspheres were prepared to improve site specificity in colonic drug delivery system. Microspheres were characterized by microscopic image analysis, DSC and IR to study the formation of microspheres structure as well as the chemical interactions between drug and polymer. Microscope observation showed good spherical and homogeneous of microspheres. The glutaraldehyde cross-linked microspheres could produce Schiff base reaction and decrease chitosan hydrogen bonding interaction with mucous membrane. The drug loading of chitosan coated-alginate microspheres reached 43% and in vitro release properties of microspheres without cecal contents reached 20.96% after 12 h. The release profiles indicated that microsphere has a satisfactory sustained release behavior. Glutaraldehyde cross-linked chitosan coated-alginate microspheres have a great potential use in drug delivery system.
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Qian, Lu, Kai Zhang, Xin Guo, Junyu Zhou, and Miao Yu. "Single-Chain Mechanical Properties of Gelatin: A Single-Molecule Study." Polymers 14, no. 5 (February 23, 2022): 869. http://dx.doi.org/10.3390/polym14050869.
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Gelatin is an important natural biological resource with a wide range of applications in the pharmaceutical, industrial and food industries. We investigated the single-chain behaviors of gelatin by atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS), and found that gelatin exists as long chains by fitting with the M-FJC model. By comparing the single-chain elasticity in a nonpolar organic solvent (nonane) and DI water, it was surprising to find that there was almost no difference in the single-chain elasticity of gelatin in nonane and DI water. Considering the specificity of gelatin solubility and the solvent size effect of nonane molecules, when a single gelatin chain is pulled into loose nonane, dehydration does not occur due to strong binding water interactions. Gelatin chains can only interact with water molecules at high temperatures; therefore, no further interaction of single gelatin chains with water molecules occurred at the experimental temperature. This eventually led to almost no difference in the single-chain F–E curves under the two conditions. It is expected that our study will enable the deep exploration of the interaction between water molecules and gelatin and provide a theoretical basis and experimental foundation for the design of gelatin-based materials with more functionalities.
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Liu, Bindong, Phuong Thi Nguyen Sarkis, Kun Luo, Yunkai Yu, and Xiao-Fang Yu. "Regulation of Apobec3F and Human Immunodeficiency Virus Type 1 Vif by Vif-Cul5-ElonB/C E3 Ubiquitin Ligase." Journal of Virology 79, no. 15 (August 1, 2005): 9579–87. http://dx.doi.org/10.1128/jvi.79.15.9579-9587.2005.
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ABSTRACT The human cytidine deaminase Apobec3F (h-A3F), a protein related to the previously recognized antiviral factor Apobec3G (h-A3G), has antiviral activity against human immunodeficiency virus type 1 (HIV-1) that is suppressed by the viral protein Vif. The mechanism of HIV-1 Vif-mediated suppression of h-A3F is not fully understood. Here, we demonstrate that while h-A3F, like h-A3G, was able to suppress primate lentiviruses other than HIV-1 (simian immunodeficiency virus from African green monkeys [SIVagm] and Rhesus macaques [SIVmac]), the interaction between Vif proteins and h-A3F appeared to differ from that with h-A3G. H-A3F showed no change in its species specificity against HIV-1 or SIVagm Vif when a negatively charged amino acid was replaced with a lysine at position 128, a residue critical for h-A3G recognition by HIV-1 Vif. However, HIV-1 Vif, but not SIVagm Vif, was able to bind h-A3F and induce its polyubiquitination and degradation through the Cul5-containing E3 ubiquitin ligase. Interference with Cul5-E3 ligase function by depletion of Cul5, through RNA interference or overexpression of Cul5 mutants, blocked the ability of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that failed to recruit Cul5-E3 ligase but was still able to interact with h-A3F failed to suppress h-A3F. Interestingly, interference with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also increased the stability of HIV-1 Vif, suggesting that like the substrate molecules h-A3F and h-A3G, the substrate receptor protein Vif is itself also regulated by Cul5-E3 ligase. Our results indicate that Cul5-E3 ligase appears to be a common pathway hijacked by HIV-1 Vif to defeat both h-A3F and h-A3G. Developing inhibitors to disrupt the interaction between Vif and Cul5-E3 ligase could be therapeutically useful, allowing multiple host antiviral factors to suppress HIV-1.
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Kolli, Nagamalleswari, Jowita Mikolajczyk, Marcin Drag, Debaditya Mukhopadhyay, Nela Moffatt, Mary Dasso, Guy Salvesen, and Keith D. Wilkinson. "Distribution and paralogue specificity of mammalian deSUMOylating enzymes." Biochemical Journal 430, no. 2 (August 13, 2010): 335–44. http://dx.doi.org/10.1042/bj20100504.
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The covalent attachment of SUMO (small ubiquitin-like protein modifier) to target proteins results in modifications in their activity, binding interactions, localization or half-life. The reversal of this modification is catalysed by SENPs (SUMO-specific processing proteases). Mammals contain four SUMO paralogues and six SENP enzymes. In the present paper, we describe a systematic analysis of human SENPs, integrating estimates of relative selectivity for SUMO1 and SUMO2, and kinetic measurements of recombinant C-terminal cSENPs (SENP catalytic domains). We first characterized the reaction of each endogenous SENP and cSENPs with HA–SUMO-VS [HA (haemagglutinin)-tagged SUMO-vinyl sulfones], active-site-directed irreversible inhibitors of SENPs. We found that all cSENPs and endogenous SENP1 react with both SUMO paralogues, whereas all other endogeneous SENPs in mammalian cells and tissues display high selectivity for SUMO2-VS. To obtain more quantitative data, the kinetic properties of purified cSENPs were determined using SUMO1- or SUMO2-AMC (7-amino-4-methylcoumarin) as substrate. All enzymes bind their respective substrates with high affinity. cSENP1 and cSENP2 process either SUMO substrate with similar affinity and catalytic efficiency; cSENP5 and cSENP6 show marked catalytic specificity for SUMO2 as measured by Km and kcat, whereas cSENP7 works only on SUMO2. Compared with cSENPs, recombinant full-length SENP1 and SENP2 show differences in SUMO selectivity, indicating that paralogue specificity is influenced by the presence of the variable N-terminal domain of each SENP. Our data suggest that SUMO2 metabolism is more dynamic than that of SUMO1 since most SENPs display a marked preference for SUMO2.
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Politi, Jane, Ilaria Rea, Fabrizia Nici, Principia Dardano, Monica Terracciano, Giorgia Oliviero, Nicola Borbone, Gennaro Piccialli, and Luca De Stefano. "Nanogravimetric and Optical Characterizations of Thrombin Interaction with a Self-Assembled Thiolated Aptamer." Journal of Sensors 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/3561863.
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Efficient biorecognition of thrombin (TB), a serine protease with crucial role in physiological and pathological blood coagulation, is a hot topic in medical diagnostics. In this work, we investigate the ability of synthetic thrombin aptamer (TBA), immobilized on a gold substrate, to bind thrombin by two different label-free techniques: the quartz crystal microbalance (QCM) and the spectroscopic ellipsometry (SE). By QCM characterization in the range from 20 to 110 nM, we demonstrate high specificity of TBA-TB interaction and determine affinity constant (Kd) of17.7±0.3 nM, system sensitivity of0.42±0.03 Hz nM−1, and limit of detection (LOD) of240±20 pM. The interaction between TBA and TB is also investigated by SE, an all-optical method, by quantifying the thickness increase of the TBA film assembled on gold substrate. AFM characterization of TBA and TB molecules deposited on flat silicon surface is also supplied.
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Liu, Tao, Zhan Xin Zhang, Huan Wei, Hong Kui Hu, and Feng Ming Wang. "The Study of Specificities of Interaction between Peptides and MHC Molecules." Advanced Materials Research 143-144 (October 2010): 1254–58. http://dx.doi.org/10.4028/www.scientific.net/amr.143-144.1254.
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Determining which peptides bind to a specific major histocompatibility complex (MHC) class I molecule is not only helpful to understand the mechanism of immunity, but also to develop effective anti-tumor epitope vaccines. In order to further study the specificity of MHC class I molecule binding antigen peptide, the support vector regression (SVR) and four amino acid descriptors were used to build four models of predicting binding affinities between peptides and MHC class I molecules. Comparison among performances of the four models indicated that the model based on physicochemical properties of amino acids is more satisfying (AC=75.0%, CC=0.499). Furthermore, the specificities of MHC class I molecule binding antigen peptide were obtained through analysis based on the contribution of the amino acids to peptide-MHC class I molecule binding affinities in the predictive model.
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Sen, Liu, and Xiao Hong Ma. "Molecular Dynamics Optimization of a Computational Model of TACE and its Substrate Peptide." Advanced Materials Research 680 (April 2013): 131–36. http://dx.doi.org/10.4028/www.scientific.net/amr.680.131.
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Tumor necrosis factor-alpha converting enzyme (TACE) is a very important membrane-bound proteinase, and it can cut a lot of membrane proteins to their released form. Many of the substrates of TACE are critical protein factors, such as IL-6, TNF-alpha, EGF receptor. Therefore, TACE has been a hopeful drug targets in many diseases. However, selective inhibitors against TACE with high specificity has yet been developed successfully, partly due to the lack of the understanding of the TACE substrate interaction details. To solve this problem, here we build a computational complex model of the TACE catalytic domain and its substrate peptide using the protein design software Rosetta. To further optimize the complex model, molecular dynamics analysis was performed in NAMD with explicit water molecules. The result showed that our complex model is a pretty reliable intermediate model for TACE and its peptide substrate. This complex model could be very useful for further study of the substrate specificity and selectivity of TACE.
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Generalov, S. V., P. S. Erokhin, T. Yu Krasovskaya, N. A. Osina, E. G. Abramova, A. K. Nikiforov, and S. A. Shcherbakova. "A STUDY OF THE ULTRASTRUCTURE OF THE SURFACE OF THE TRANSPLANTABLE LINE VERO CELLS INFECTED WITH THE RABIES VIRUS (RABV, LISSAVIRUS, RHABDOVIRIDAE)." Problems of Virology, Russian journal 62, no. 5 (October 20, 2017): 227–32. http://dx.doi.org/10.18821/0507-4088-2017-62-5-227-232.
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Characteristics of the effect of attenuated rabies virus strain «Moscow 3253» on morphological parameters of transplantable line Vero cells were studied by atomic force microscopy (AFM). Methods based on phase contrast microscopy and immunofluorescence were used to confirm the specificity of interaction and to identify the infectious activity of the rabies virus. Images of intact Vero cells and Vero cells infected with rabies virus were obtained at different periods of cultivation. The character of changes in the cell dimensions (length, width, height) and the cell membrane roughness depending on the rabies virus cultivation time was determined. During the observation period both increases and decreases in the size of the cells were recorded. The size of the infected cells exceeded that of the intact. An increase in the membrane roughness in cells exposed to rabies occurred during the entire period of observation, since the first hours of the interaction of the virus with the cell, while the intact Vero cells exhibited only minor changes in the membrane surface roughness, which were not dependent on the age of the culture. The dependence of the increase in the cell membrane roughness on the infecting dose of the rabies virus was determined. The obtained results open up the prospect of developing a methodological approach to the quantitative in vitro evaluation of the rabies virus using AFM. Changes in the cell membrane roughness appear to be the most indicative parameter for such evaluation.
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Gvaldin, Dmitry Yu, Natalya N. Timoshkina, Larisa N. Vashchenko, Tatiana V. Ausheva, Irina R. Dashkova, Ludmila A. Ryadinskaya, Emma E. Kechedzhieva, and Liubov Yu Vladimirova. "SNP-SNP interactions and a 4-locus model for prediction the risk of anthracycline-mediated cardiotoxicity in patients with breast cancer." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 12076. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.12076.
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12076 Background: Numerous pharmacogenetic studies have identified genetic polymorphisms (SNPs) associated with an increased risk of anthracycline-mediated cardiotoxicity (AMC). The purpose was to search for SNP-SNP interactions associated with the risk of cardiotoxic manifestations caused by anthracycline therapy in breast cancer patients. Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer with normal cardiovascular system parameters at baseline, who were treated with anthracyclines in 2019-2020. For SNP genotyping of c.4544G > A rs8187710 (ABCC2), c.1744C > T rs11549465 ( HIF1A), g.22125504G > C rs1333049 ( CDKN2A/ B) and c.214T > C rs4673 ( CYBA). DNA was extracted from blood by using DNA-sorb-B (AmpliSens, Russia). HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by the Sanger method on a Genetic Analyzer 3500 (ABI, USA). Results: During the follow-up period 21 (8.2%) patients developed signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic anthracycline mediated cardiotoxicity (changes developed within a year after completion of anthracycline therapy). Using the multifactorial dimension reduction method. We obtained a 4-locus model of SNP-SNP interactions c.4544G > A rs8187710 ( ABCC2) x g.22125504G > C rs1333049 ( CDKN2A/B) x c.214T > C rs4673 ( CYBA) x g.23708527G > A rs28714259 which has high prognostic properties. The specificity of the test based on the 4-locus model was 68%, the sensitivity was 100%, and the overall accuracy was 71%. The results of the analysis of SNP-SNP interactions indicate the greatest contribution of rs4673 and rs28714259 to the predisposition to AMC. The first ones yet into antagonistic interactions with rs28714259, rs1333049 and rs11549465, the second with rs8187710, rs11549465 and rs4673. On the contrary rs11549465 and rs1333049 contribute to a synergistic effect. Conclusions: The 4-locus model discovered in this study can form the basis of prognostic tests that predict early the risks of developing AMC in cancer patients, which in the future allow to personalize and select the most optimal treatment regimen.
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Lu, Xiu Li, Shu Chao Chen, Yong Zhang, Li Zhang, Hong Sheng Liu, and Bing Gao. "The Discovery of Direct Noncovalent Bonded Interaction between Keap1 and Diethyl Maleate through Molecular Dynamics Simulations." Applied Mechanics and Materials 192 (July 2012): 260–65. http://dx.doi.org/10.4028/www.scientific.net/amm.192.260.
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Keap1 negatively regulates the function of Nrf2 that is a major activator of genes encoding phase 2 detoxifying enzymes via sequestering cytoplasmic Nrf2 and subsequent degradation through the proteasome system. Reactive cysteine residues of Keap1 could be modified by Michael reaction acceptor molecules. Previous studies have shown that adduction at Cys151 by diethyl maleate (DEM) can give rise to a significant conformational change in Keap1 that leads to the dissociation of Keap1 from CUL3, hence inhibits Nrf2 ubiquitylation. The BTB domain of Keap1 plays a crucial role in both forming self-dimerization and binding to CUL3. In order to better understanding the molecular mechanism how DEM interact with amino acid residues around Cys151, we performed two molecular dynamics (MD) simulations including Keap1-DEM complex and Keap1 alone (control group). Interestingly, we found that after a short period of lingering around Cys151, DEM ultimately stabilized in a gap between two specific helixes away from the cavity around Cys151 and induced a concomitant significant conformational change of BTB domain of Keap1. Similar phenomenon, however, was not observed in the control group. These results suggested that DEM could impair the normal function of Keap1 by inducing the conformational change of BTB domain via direct noncovalent bonded interaction. Our research provides a new insight into another way of interaction between Keap1 and DEM in spite of their known Michael addition reaction, by which novel phase2 enzyme inducer drugs with higher specificity could be discovered in the future
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Zhang, Yan Ling, Yuan Ming Wang, and Yan Jiang Qiao. "Sub-Pharmacophore Generation of JNK3 Inhibitors." Applied Mechanics and Materials 444-445 (October 2013): 1756–60. http://dx.doi.org/10.4028/www.scientific.net/amm.444-445.1756.
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The structure-based pharmacophore (SBP) model is consisted by the complementarity of the chemical features and space of the interaction between the ligand and receptor. The SBP models always have a high specificity which can only represent the specific class of the ligand. To simplify the models, sub-pharmacophore was then proposed in present study, and was expected to have and only have the most important or the common chemical features which play the major role in the interaction of ligand and receptor. Sub-pharmacophore should contain 4-6 features, the higher specificity with more features, and vice versa. The sub-pharmacophore was generated by the random combination of features from the structure-based models. With the MDL Drug Data Report database used as the testing database, a new metric CAI (comprehensive appraisal index), which integrated the metrics of E and A%, was defined and used to determine the best sub-pharmacophore model. C-Jun N-terminal kinase (JNKs) is one of the mitogen-activated protein kinase family, and widely involved in immune response and inflammatory response, and other pathological processes. JNK3 is mainly distributed in the brain and nervous system. In present study, twenty-five initial SBP models of JNK3 inhibitors were directly constructed from the Protein Data Bank (PDB) complexes by the LigandScout software. Then, 1018 sub-pharmacophore models were obtained from the 25 initial models. Finally, the best sub-pharmacophore was determined which was simplified from the initial model generated from the 3FI2 complex, and included four features: one hydrogen bond donor, one hydrogen bond acceptor, and two hydrophobic groups. The metrics of E, A% and CAI value of the best sub-pharmacophore model are 17.47, 31.15 and 5.44, respectively. The potential JNK3 inhibitors were then identified from Chinese herbs with the best sub-pharmacophore model, and 286 compounds were obtained.
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Vasilev, Cvetelin, Guy E. Mayneord, Amanda A. Brindley, Matthew P. Johnson, and C. Neil Hunter. "Dissecting the cytochrome c2–reaction centre interaction in bacterial photosynthesis using single molecule force spectroscopy." Biochemical Journal 476, no. 15 (August 9, 2019): 2173–90. http://dx.doi.org/10.1042/bcj20170519.
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Abstract The reversible docking of small, diffusible redox proteins onto a membrane protein complex is a common feature of bacterial, mitochondrial and photosynthetic electron transfer (ET) chains. Spectroscopic studies of ensembles of such redox partners have been used to determine ET rates and dissociation constants. Here, we report a single-molecule analysis of the forces that stabilise transient ET complexes. We examined the interaction of two components of bacterial photosynthesis, cytochrome c2 and the reaction centre (RC) complex, using dynamic force spectroscopy and PeakForce quantitative nanomechanical imaging. RC–LH1–PufX complexes, attached to silicon nitride AFM probes and maintained in a photo-oxidised state, were lowered onto a silicon oxide substrate bearing dispersed, immobilised and reduced cytochrome c2 molecules. Microscale patterns of cytochrome c2 and the cyan fluorescent protein were used to validate the specificity of recognition between tip-attached RCs and surface-tethered cytochrome c2. Following the transient association of photo-oxidised RC and reduced cytochrome c2 molecules, retraction of the RC-functionalised probe met with resistance, and forces between 112 and 887 pN were required to disrupt the post-ET RC–c2 complex, depending on the retraction velocities used. If tip-attached RCs were reduced instead, the probability of interaction with reduced cytochrome c2 molecules decreased 5-fold. Thus, the redox states of the cytochrome c2 haem cofactor and RC ‘special pair’ bacteriochlorophyll dimer are important for establishing a productive ET complex. The millisecond persistence of the post-ET cytochrome c2[oxidised]–RC[reduced] ‘product’ state is compatible with rates of cyclic photosynthetic ET, at physiologically relevant light intensities.
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Xia, Xiong, Huang Xu, Ai Qin Zhang, Li Qian, and Kai Huang. "Research on Variation of Land Subsidence in Changzhou." Applied Mechanics and Materials 256-259 (December 2012): 463–66. http://dx.doi.org/10.4028/www.scientific.net/amm.256-259.463.
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Land subsidence as one of geological disasters, due to the characteristics and specificity hydrogeology, which results in the differences of subsidence in different regions. Changzhou City, in Jiangsu province, in China, underlain by a multi-layered aquifer system in Quaternary sediments in the Great Yangtze River Delta region. Take into account geological characteristics and mechanisms, the Changzhou layers can be divided respectively into four soil stratifications: phreatic aquifer, Part I aquifer ,Part II aquifer ,and substratum. According to the monitoring data of bedrock bench mark at Changzhou Qingliang primary school, get the mechanism of water-soil interaction and the law between land subsidence and water level change, and establishes numerical coupling model and simulates, that can evaluate and predict Changzhou land subsidence.
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Hu, Kongzhen, Li Li, Yong Huang, Shimin Ye, Jiawei Zhong, Qingsong Yan, Yuhua Zhong, Lilan Fu, Pengju Feng, and Hongsheng Li. "Radiosynthesis and Preclinical Evaluation of Bispecific PSMA/FAP Heterodimers for Tumor Imaging." Pharmaceuticals 15, no. 3 (March 21, 2022): 383. http://dx.doi.org/10.3390/ph15030383.
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Due to tumor heterogeneity and complex tumor–stromal interactions in multicellular systems, the efficiency of monospecific tracers for tumor diagnosis and therapy is currently limited. In light of the evidence of prostate-specific membrane antigen (PSMA) overexpression in tumor cells and fibroblast activation protein (FAP) upregulation in the tumor stroma, heterodimer dual targeting PSMA and FAP may have the potential to improve tumor diagnosis. Herein, we described the radiosynthesis, in vitro characterization, and micro-PET/CT imaging of two novel 18F-labeled bispecific PSMA/FAP heterodimers. 18F-labeled heterodimers showed high specificity and affinity targeting to PSMA and FAP in vitro and in vivo. Compared with the monospecific tracers [18F]AlF-PSMA-BCH and [18F]FAPI-42, both 18F-labeled heterodimers exhibited better tumor uptake in tumor-bearing mice. Their favorable characterizations such as convenient synthesis, high tumor uptake, and favorable pharmacokinetic profile could lead to their future applications as bispecific radiotracers for clinical cancer imaging.
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Ma, Fu Rong, Xin Gui Zhang, and Nian Ping Yi. "Analysis of Influence Factors on Strength of Mudstone with Soft-Hard Alternant Strata in Nanning Basin." Advanced Materials Research 204-210 (February 2011): 891–94. http://dx.doi.org/10.4028/www.scientific.net/amr.204-210.891.
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The mudstone is formed under the special environment with soft-hard alternant strata in Nanning Basin . The composition,engineering and mechanical properties have a certain complexity and specificity,so the parameters of the mudstone are discrete and variable by which the strength characteristics are influenced. According to the problem of the strength of mudstone,the influence factor is analysed on the strength of mudstone with soft-hard alternant strata in Nanning Basin through the composition, stress history, geological environment, water-rock interaction and disturbance, etc.. The analysis shows that in the final analysis the reduction of the mechanical properties of mudstone is due to structural damage, stress weakening and energy weakening.And the measures of improving the bearing capacity of mudstone are discussed from the test methods, construction control measures, in situ testing and engineering design.
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RUNGROTMONGKOL, THANYADA, SUPA HANNONGBUA, and ADRIAN MULHOLLAND. "MECHANISTIC STUDY OF HIV-1 REVERSE TRANSCRIPTASE AT THE ACTIVE SITE BASED ON QM/MM METHOD." Journal of Theoretical and Computational Chemistry 03, no. 04 (December 2004): 491–500. http://dx.doi.org/10.1142/s0219633604001252.
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HIV-1 RT catalyses the reverse transcription of viral genetic material (RNA) into double-stranded DNA, and is an important target of antiviral therapy in the treatment of AIDS. Better understanding of the structure, mechanism and functional role of residues involved in the resistance of HIV-1 RT against nucleoside-analog drugs may assist in the development of improved inhibitors, and also in understanding the effects of genetic variation on RT specificity and activity. In this study, firstly, molecular dynamics simulations (with CHARMM27) have been used to investigate binding interactions at the active site and the conformational behavior of the enzyme, then, mechanisms of deprotonation and DNA polymerization reactions have been modelled by the QM/MM method. A combined quantum mechanical and molecular mechanical (QM/MM) method (AM1/CHARMM) has been used to study the triphosphate substrate and the active site of HIV-1 reverse transcriptase complex structure, a virally-encoded enzyme. Free energy profiles for the reaction are also calculated. The obtained results provide important insight into the mechanistic activity of HIV-1 RT.
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Foti, Antonino, Suriya Venkatesan, Bérengère Lebental, Gaël Zucchi, and Razvigor Ossikovski. "Comparing Commercial Metal-Coated AFM Tips and Home-Made Bulk Gold Tips for Tip-Enhanced Raman Spectroscopy of Polymer Functionalized Multiwalled Carbon Nanotubes." Nanomaterials 12, no. 3 (January 28, 2022): 451. http://dx.doi.org/10.3390/nano12030451.
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Tip-enhanced Raman spectroscopy (TERS) combines the high specificity and sensitivity of plasmon-enhanced Raman spectroscopy with the high spatial resolution of scanning probe microscopy. TERS has gained a lot of attention from many nanoscience fields, since this technique can provide chemical and structural information of surfaces and interfaces with nanometric spatial resolution. Multiwalled carbon nanotubes (MWCNTs) are very versatile nanostructures that can be dispersed in organic solvents or polymeric matrices, giving rise to new nanocomposite materials, showing improved mechanical, electrical and thermal properties. Moreover, MWCNTs can be easily functionalized with polymers in order to be employed as specific chemical sensors. In this context, TERS is strategic, since it can provide useful information on the cooperation of the two components at the nanoscale for the optimization of the macroscopic properties of the hybrid material. Nevertheless, efficient TERS characterization relies on the geometrical features and material composition of the plasmonic tip used. In this work, after comparing the TERS performance of commercial Ag coated nanotips and home-made bulk Au tips on bare MWCNTs, we show how TERS can be exploited for characterizing MWCNTs mixed with conjugated fluorene copolymers, thus contributing to the understanding of the polymer/CNT interaction process at the local scale.
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Shi, Ya Min, Guo Guang Rong, Dan Ni Wang, Shu Lin Zhang, and Yong Xin Zhu. "A Label-Free Biosensor Based on Nanoscale Porous Silicon Thin Film for Tuberculosis Detection." Advanced Materials Research 1082 (December 2014): 555–61. http://dx.doi.org/10.4028/www.scientific.net/amr.1082.555.
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Though techniques in medicine develop in a very fast pace, tuberculosis still bothers researchers for its extensive existence. It is urgent to find faster, cheaper and more convenient new ways for diagnosis of tuberculosis. In this paper, we demonstrated a novel serodiagnostic method based on porous silicon thin film. Porous silicon has been proven feasible to function as biosensors in a lot of research. While most serodiagnostic methods are labeled detection, our porous silicon biosensor is a label-free technique. This kind of biosensor is manufactured in a simple way with relatively lower cost while providing an excellent sensitivity and specificity. Through the experiment of LAM antigen and anti-LAM antibody interacting on a porous silicon thin film platform, we proved the feasibility of our new detection approach. Furthermore, we also provided some innovation insights for improving our biosensor which may help it be practically applicable.
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Ruiz-Sanmartín, Adolfo, Vicent Ribas, David Suñol, Luis Chiscano-Camón, Clara Palmada, Iván Bajaña, Nieves Larrosa, et al. "Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock." PLOS ONE 17, no. 12 (December 2, 2022): e0278708. http://dx.doi.org/10.1371/journal.pone.0278708.
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Introduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality.
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Sun, Ping Ping, Wen Han Chen, Xing Wang, Bo Liu, and Ying Hua Lv. "Prediction of Antigen Epitopes on Protein Surfaces Based on Support Vector Machine." Advanced Materials Research 393-395 (November 2011): 884–89. http://dx.doi.org/10.4028/www.scientific.net/amr.393-395.884.
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B-cell epitope prediction is important for vaccine design, development of diagnostic reagents and for studies to elucidate the interactions between antigen and antibody on a molecular level. Here, we present a new epitope prediction method based on six different scoring functions and exploited LibSVM to predict the antigenic epitopes in protein surface. Using bound structures of the testing dataset, the method was able to predict antigenic epitopes with 50.6% sensitivity, 62.9% specificity, 19% precision and an AUC value of 0.616. While using unbounded structures of the testing dataset, the performance of the method was nearly the same. Compared with another epitope prediction method EPCES, the performance of the method is statistically similar. The results suggest that more effective features that discriminate epitopes from non-epitopes may further improve the performance of the prediction method. Also, the new algorithms for predicting the epitopes are desired and the construction of large with non-redundant datasets is strongly needed.
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Vasudevan, Ananda Ayyappan Jaguva, Sander H. J. Smits, Astrid Höppner, Dieter Häussinger, Bernd W. Koenig, and Carsten Münk. "Structural features of antiviral DNA cytidine deaminases." Biological Chemistry 394, no. 11 (November 1, 2013): 1357–70. http://dx.doi.org/10.1515/hsz-2013-0165.
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Abstract The APOBEC3 (A3) family of cytidine deaminases plays a vital role for innate defense against retroviruses. Lentiviruses such as HIV-1 evolved the Vif protein that triggers A3 protein degradation. There are seven A3 proteins, A3A-A3H, found in humans. All A3 proteins can deaminate cytidines to uridines in single-stranded DNA (ssDNA), generated during viral reverse transcription. A3 proteins have either one or two cytidine deaminase domains (CD). The CDs coordinate a zinc ion, and their amino acid specificity classifies the A3s into A3Z1, A3Z2, and A3Z3. A3 proteins occur as monomers, dimers, and large oligomeric complexes. Studies on the nature of A3 oligomerization, as well as the mode of interaction of A3s with RNA and ssDNA are partially controversial. High-resolution structures of the catalytic CD2 of A3G and A3F as well as of the single CD proteins A3A and A3C have been published recently. The NMR and X-ray crystal structures show globular proteins with six α-helices and five β sheets arranged in a characteristic motif (α1-β1-β2/2′-α2-β3-α3-β4-α4-β5-α5-α6). However, the detailed arrangement and extension of individual structure elements and their relevance for A3 complex formation and activity remains a matter of debate and will be highlighted in this review.
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Talusan, Timothy Jemuel E., Maria Crispina P. Baltazar, Ken Aldren S. Usman, and Leon M. Payawan Jr. "Synthesis of Glucose-Sensitive Microcapsules via Layer-by-Layer Assembly for Controlled Insulin Release Applications." Applied Mechanics and Materials 863 (February 2017): 84–88. http://dx.doi.org/10.4028/www.scientific.net/amm.863.84.
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Drug delivery systems using polymeric materials have been under intensive investigation and have been reported to show effective drug targeting specificity, lowering system drug toxicity, improving treatment absorption rates, and providing enteric coatings against biochemical degradation. The layer–by–layer (Lbl) assembly of polyelectrolytes through electrostatic interactions can be readily tailored to control the size, structure, and stability of the film and microcapsules. In this study, microcapsules were fabricated by alternately depositing poly (dimethyldiallylammonium chloride) PDDA, glucose oxidase (GOx), and polyacrylic acid (PAA) to form multilayer shells on a MnCO3 template and onto insulin particles by Lbl method. Also, the physical characteristic and release mechanism of thin films incorporating insulin sandwiched between [2(dimethyl amino) ethyl methacrylate] (PDMAEMA), with polymer/GOx layers were compared with the fabricated microcapsules. The synthesized shells have shown stability at pH 4 and become unstable at neutral pH. The fabricated insulin loaded microcapsules and films showed an on–off mechanism in the presence of glucose. Exposure to glucose solutions resulted in the production of gluconic acid; as a result, there was a change in the conformation of the polymer, releasing the embedded insulin. The drug release profiles observed indicates their potential application for the controlled release of insulin.
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Urdinola, Kaory Barrientos, Paula Andrea Marín Muñoz, Pedronel Araque Marín, and Marisol Jaramillo Grajales. "In-Silico Prediction on the MSAMS-Assisted Immobilization of Bovine Serum Albumin on 10MHz Piezoelectric Immunosensors." Journal of Molecular and Engineering Materials 07, no. 01n02 (March 2019): 1950001. http://dx.doi.org/10.1142/s2251237319500011.
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The biological sensing interface on the active area of a piezo transducer is responsible for the sensitivity, specificity, reusability, and reproducibility of these devices. Among the approaches used to functionalize piezo transducers, mixed self-assembled monolayers (MSAMs) are one of the most successful, given that they allow the obtaining of semi-crystalline molecular arrays and the arrangement of a bioreceptor on the surface. But, to deploy MSAMs on a substrate effectively, one must optimize and characterize the structural ratio between them and the bioreceptor. In this paper, we developed a molecular model of the interaction between Bovine Serum Albumin (BSA) and MSAMs-functionalized gold substrates. First, we evaluated the conditions for the functionalization of the substrates and found that a 50:1 16-mercaptohexadecaonic acid (MHDA) to 11 mercapto-1-undecanol (MUA) ratio produced the best features on the surface. We also evaluated the specific conditions to immobilize BSA on MSAMs (using the afore-established ratio) via Atomic Force Microscopy (AFM), and then on a 10[Formula: see text]MHz quartz crystal microbalance (QCM), and with the data obtained we concluded that a structural ratio of 0.005 (MSAM/BSA) is obtained when 1[Formula: see text][Formula: see text]M MHDA and 200[Formula: see text][Formula: see text]g/mL BSA were used, provided the most suitable conditions for the functionalization of a piezo transducer.
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Mozhaev, Andrey, Evgeny Pichkur, Igor Deyev, Ekaterina Mileshina, Anton Orekhov, Alexander Vasiliev, and Alexander Petrenko. "Abstract P-13: Structural Studies of Insulin Receptor-Related Receptor Ectodomain." International Journal of Biomedicine 11, Suppl_1 (June 1, 2021): S16—S17. http://dx.doi.org/10.21103/ijbm.11.suppl_1.p13.
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Background: The insulin receptor-related receptor (IRR) was originally discovered due to its high homology to the other family members (insulin receptor and insulin-like growth factor 1 receptor). We determined that IRR can be activated by mildly alkaline extracellular media and has typical features of the ligand-receptor interaction, including its specificity and dose-dependence. Since pH-sensitive properties of IRR are determined by its ectodomain; therefore, we chose as an option to study the soluble extracellular domain IRR. Methods: The investigation carried out in Titan Krios 60-300 TEM/STEM (FEI, USA) CryoEM, equipped with direct electron detector Falcon II (FEI, USA) and Cs image corrector (CEOS, Germany), at an accelerating voltage of 300 kV. Data processing and 3D reconstruction were carried out using computing resources of the Federal Collective Usage Center Complex for Simulation and Data Processing for Mega-Science Facilities at NRC “Kurchatov Institute.” Results: The obtained 2D classifications of particles of the ectodomain IRR at a neutral pH form several 3D models. This indicates that the ectodomain has several possible conformations, which is consistent with our previously obtained data using SEC-SAXS and AFM. In the future, additional careful data processing is required, as well as studies of the IRR ectodomain in mildly alkaline pH. Conclusion: In this study, we presented the structural characteristics of the IRR ectodomain obtained by CryoEM. These results are an important step towards understanding the mechanism of functioning of the IRR.
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Yu, Lu. "Abstract 303: Thiol-mediated rapid cytosolic uptake of tumor-targeted DNA nanorobot for siRNA delivery." Cancer Research 82, no. 12_Supplement (June 15, 2022): 303. http://dx.doi.org/10.1158/1538-7445.am2022-303.
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Abstract Most FDA approved anticancer drugs rely on passive delivery for cellular uptake, which will compromise therapeutic efficacy and lead to off-target-associated toxicity. DNA nanostructures are promising drug delivery platforms for targeted cancer therapy due to their highly programmable molecular interactions, precisely defined geometry, stoichiometry, as well as outstanding biocompatibility. However, most DNA nanostructures are taken up by cells through endocytosis pathway, resulting in the subsequent endo- and lysosomal trapping and degradation. Here we design a smart DNA nanorobot that will go through endocytosis-independent pathway with tumor target specificity and therapeutic effects for the treatment of breast cancer. It has been reported that disulfide units are able to mediate cytosolic uptake of DNA and RNA molecules by disulfide exchange reactions with thiol groups on the cell membrane protein. Therefore, we site-specifically modify disulfide units onto the inside surface of DNA nanorobot. 24-helix DNA origami nanotube is used as drug delivery vehicle. To achieve target specificity, we use HER2 affibody, a short peptide that has high binding affinity [KD=22pM] to HER2 protein that overexpressed on the cell membrane of breast cancer cells, and truncated HER2 protein as a temporary lock-and-key to close DNA nanorobot. In this way, DNA nanorobot can only be opened when it reaches tumor cells that overexpress HER2 protein which has a higher binding affinity to HER2 affibody. The inner disulfide units will be exposed to mediate cytosolic uptake of DNA nanorobot. To achieve potent therapeutic effect, we use therapeutic siRNAs/shRNAs as drugs due to their efficient target gene silencing, splice modulation and gene activation potentials. Cytosolic uptake of siRNAs/shRNAs by DNA nanorobot could maximize their target knockdown effect since siRNAs/shRNAs silencing occurs primarily in the cytoplasm. We use atomic force microscope (AFM), transmission electron microscope (TEM), agarose gel electrophoresis and fluorimeter to characterize the formation of the DNA nanorobot. The cellular uptake of DNA nanorobot is evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Use RT-qPCR and western blot to test the gene and protein knockdown effect. In the future, we will do in vivo experiment on tumor xenograft mice and assess the antitumor effect of DNA nanorobot. Our current results demonstrated that DNA origami modified with disulfide units can directly get internalized into the cytoplasm of cells. In addition, protecting disulfide units inside the DNA origami nanotube can block the cytosolic uptake. Therefore, our DNA nanorobot has the potential to be an efficient and safe drug delivery platform for cancer therapeutics. Citation Format: Lu Yu. Thiol-mediated rapid cytosolic uptake of tumor-targeted DNA nanorobot for siRNA delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 303.
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Guo, Xin, Ping Wang, Xinjie Wang, Yaoming Li, and Baoming Ji. "Specific Plant Mycorrhizal Responses Are Linked to Mycorrhizal Fungal Species Interactions." Frontiers in Plant Science 13 (June 10, 2022). http://dx.doi.org/10.3389/fpls.2022.930069.
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Effects of arbuscular mycorrhizal fungi (AMF) on plants span the continuum from mutualism to parasitism due to the plant–AMF specificity, which obscures the utilization of AMF in the restoration of degraded lands. Caragana korshinskii, Hedysarum laeve, Caragana microphylla, and Poa annua are the most frequently used plants for revegetation in Kubuqi Desert, China, and the influence of AMF on their re-establishment remains to be explored further. Herein, using a greenhouse experiment, we tested the plant–AMF feedbacks between the four plant species and their conspecific or heterospecific AMF, retrieved from their rhizosphere in the Kubuqi Desert. AMF showed beneficial effects on plant growth for all these plant-AMF pairs. Generally, AMF increased the biomass of C. korshinskii, H. laeve, C. microphylla, and P. annua by 97.6, 50.6, 46.5, and 381.1%, respectively, relative to control. In addition, the AMF-plant specificity was detected. P. annua grew best, but C. microphylla grew worst with conspecific AMF communities. AMF community from P. annua showed the largest beneficial effect on all the plants (with biomass increased by 63.9–734.4%), while the AMF community from C. microphylla showed the least beneficial effect on all the plants (with biomass increased by 9.9–59.1%), except for P. annua (a 292.4% increase in biomass). The magnitude of AMF effects on plant growth was negatively correlated with the complexity of the corresponding AMF co-occurrence networks. Overall, this study suggests that AMF effects on plant growth vary due to plant-AMF specificity. We also observed the broad-spectrum benefits of the native AMF from P. annua, which indicates its potential utilization in the restoration of the desert vegetation.
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Razak, Nadia Ab, and Alan C. Gange. "Multitrophic Interactions Between Arbuscular Mycorrhizal Fungi, Foliar Endophytic Fungi and Aphids." Microbial Ecology, December 13, 2021. http://dx.doi.org/10.1007/s00248-021-01937-y.
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AbstractAlmost all living plants can be simultaneously colonised by arbuscular mycorrhizal fungi in the roots and endophytes in the shoots, while also being attacked by insect herbivores. However, to date, no study has ever examined the multitrophic interactions between these two different fungal groups and insects on any species of forb. Here, we examined the effects of two commercial species mixtures of arbuscular mycorrhizal fungi (AMF) and two foliar endophytes (Colletotrichum acutatum and Cladosporium oxysporum) on the growth of an invasive weed, Impatiens glandulifera, and the aphids that attack it. AMF reduced plant biomass, which was most evident when C. oxysporum was inoculated. Mycorrhizal fungi had few effects on aphids, and these depended on the identity of the endophytes present. Meanwhile, endophytes tended to increase aphid numbers, but this depended on the identity of the AMF inoculum. Throughout, there were differences in the responses of the plant to the two mycorrhizal mixtures, demonstrating clear AMF specificity in this plant. These specific effects were also strongly affected by the endophytes, with a greater number of interactions found between the AMF and endophytes than between the endophytes themselves. In particular, AMF reduced infection levels by the endophytes, while some endophyte inoculations reduced mycorrhizal colonisation. We suggest that both AMF and endophytes could play an important part in future biological control programmes of weeds, but further multitrophic experiments are required to unravel the complexity of interactions between spatially separated parts of the plant microbiome.
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Zhao, Zhongtao, Xiaojuan Li, Ming Fai Liu, Vincent S. F. T. Merckx, Richard M. K. Saunders, and Dianxiang Zhang. "Specificity of assemblage, not fungal partner species, explains mycorrhizal partnerships of mycoheterotrophic Burmannia plants." ISME Journal, January 6, 2021. http://dx.doi.org/10.1038/s41396-020-00874-x.
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AbstractMycoheterotrophic plants (MHPs) growing on arbuscular mycorrhizal fungi (AMF) usually maintain specialized mycorrhizal associations. The level of specificity varies between MHPs, although it remains largely unknown whether interactions with mycorrhizal fungi differ by plant lineage, species, and/or by population. Here, we investigate the mycorrhizal interactions among Burmannia species (Burmanniaceae) with different trophic modes using high-throughput DNA sequencing. We characterized the inter- and intraspecific dynamics of the fungal communities by assessing the composition and diversity of fungi among sites. We found that fully mycoheterotrophic species are more specialized in their fungal associations than chlorophyllous species, and that this specialization possibly results from the gradual loss of some fungal groups. In particular, although many fungal species were shared by different Burmannia species, fully MHP species typically host species-specific fungal assemblages, suggesting that they have a preference for the selected fungi. Although no apparent cophylogenetic relationship was detected between fungi and plants, we observe that evolutionarily closely related plants tend to have a greater proportion of shared or closely related fungal partners. Our findings suggest a host preference and specialization toward fungal assemblages in Burmannia, improving understanding of interactions between MHPs and fungi.
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Fernandes, Kenya, Evelyne Desplazes, Sameer Kulkarni, Richard Payne, and Dee Carter. "S3.4b Lactoferrin, a natural source of peptides that potentiate the antifungal activity of amphotericin B." Medical Mycology 60, Supplement_1 (September 2022). http://dx.doi.org/10.1093/mmy/myac072.s3.4b.
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Abstract S3.4 Free oral paper session, September 21, 2022, 4:45 PM - 6:15 PM Objectives It is notoriously difficult to prevent and treat fungal infections, however, the natural world has come up with remedies that are non-toxic, effective, and evade resistance. Here we investigate lactoferrin, an iron-binding glycoprotein found in milk, tears, and sweat, for its capacity to inhibit fungi and to synergize with commonly used antifungal drugs, with the aim of determining its mode of action. Methods Lactoferrin (LF) was obtained from a commercial supplier and two dairy companies. LF was tested on suite of pathogenic yeast and mold species for inhibition using CLSI microdilution methods. Synergy was determined with antifungal drugs amphotericin B (AMB), nystatin (NYS), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), and 5-fluorocytosine (5FC). The effect of LF on fungal cells was analyzed using scanning electron microscopy (SEM). The active peptide/s within LF were then predicted from pepsin and in silico digestion, synthesized, and tested for synergy with amphotericin B (AMB). Tethered synthetic membranes were produced and were loaded with ergosterol or cholesterol to test the nature and specificity of membrane binding by LF and the synthetic peptide. Results LF demonstrated antifungal activity against yeast species Cryptococcus, Candida, and Saccharomyces and was much less effective against molds. Good synergy was achieved with AMB but not azole or echinocandin drugs. While the iron-chelating capacity of LF was important for the antifungal activity it was not involved in synergy. SEM revealed cell damage suggesting an interaction between AMB, LF and the fungal membrane or cell wall. A 30-residue peptide from the C lobe of LF was synthesized and tested for activity and synergy. This peptide, dubbed lactofungin (LFG) was inactive alone but was potently synergistic with AMB, indicating a direct role in augmenting AMB activity. Synthetic membranes loaded with ergosterol but not cholesterol were disrupted by AMB + LFG, demonstrating that activity was fungal-specific and was mediated through ergosterol binding. Conclusion LF is a complex molecule that causes fungal inhibition via iron binding and when cleaved by pepsin can produce active peptides. As AMB is a highly toxic treatment, the use of LFG as a synergent could help increase activity while lowering the effective dose, thereby reducing undesirable side effects. The action of AMB + LFG appears dependent on ergosterol, suggesting inhibition will be highly fungal-specific.
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Crowe, Jacob D., Pengchao Hao, Sivakumar Pattathil, Henry Pan, Shi-You Ding, David B. Hodge, and Jacob Krüger Jensen. "Xylan Is Critical for Proper Bundling and Alignment of Cellulose Microfibrils in Plant Secondary Cell Walls." Frontiers in Plant Science 12 (September 23, 2021). http://dx.doi.org/10.3389/fpls.2021.737690.
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Plant biomass represents an abundant and increasingly important natural resource and it mainly consists of a number of cell types that have undergone extensive secondary cell wall (SCW) formation. These cell types are abundant in the stems of Arabidopsis, a well-studied model system for hardwood, the wood of eudicot plants. The main constituents of hardwood include cellulose, lignin, and xylan, the latter in the form of glucuronoxylan (GX). The binding of GX to cellulose in the eudicot SCW represents one of the best-understood molecular interactions within plant cell walls. The evenly spaced acetylation and 4-O-methyl glucuronic acid (MeGlcA) substitutions of the xylan polymer backbone facilitates binding in a linear two-fold screw conformation to the hydrophilic side of cellulose and signifies a high level of molecular specificity. However, the wider implications of GX–cellulose interactions for cellulose network formation and SCW architecture have remained less explored. In this study, we seek to expand our knowledge on this by characterizing the cellulose microfibril organization in three well-characterized GX mutants. The selected mutants display a range of GX deficiency from mild to severe, with findings indicating even the weakest mutant having significant perturbations of the cellulose network, as visualized by both scanning electron microscopy (SEM) and atomic force microscopy (AFM). We show by image analysis that microfibril width is increased by as much as three times in the severe mutants compared to the wild type and that the degree of directional dispersion of the fibrils is approximately doubled in all the three mutants. Further, we find that these changes correlate with both altered nanomechanical properties of the SCW, as observed by AFM, and with increases in enzymatic hydrolysis. Results from this study indicate the critical role that normal GX composition has on cellulose bundle formation and cellulose organization as a whole within the SCWs.
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"Peculiarities of psychotherapeutic work with traumatic emotional experience of combatants." Psychological Counseling and Psychotherapy, no. 8 (2017). http://dx.doi.org/10.26565/2410-1249-2017-8-02.
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This article introduces the features of psychotherapeutic work with the traumatic emotional experience among combatants. The applicability of this issue has sharply increased over the past 3-4 years, primarily due to the events in eastern Ukraine, namely, the Antiterrorist Operation (ATO), which determined the growth of combatants with different features of emotional trauma. The specific conditions for the combatants, the peculiarities of communication with the executives, subordinates and comrades, the features of the traumatic emotional experience, the importance of working with emotional structures, pointed out by O.S. Kocharian and his students in numerous researches, make it necessary to develop a psychotherapeutic strategy for working with combatants. The article considers the possibility of using client-centered psychotherapy as a core component of therapy, complemented by elements of cognitive psychotherapy, psychotherapy by A.F. Yermoshin, and the direction proposed by David Berceli, namely TRE - Trauma & Tension Releasing Exercises, which in general give the opportunity to avoid possible destructive specificity of interaction with clients-combatants-men. A possible specificity of therapeutic work with women is not considered. Characteristics of the emotional traumatic experience among combatants, based on a concrete example of therapeutic practice is: fragmentation of memories, "gluing of emotions and feelings", loss of connection between meaning and emotion, dissociation from certain emotions (fear, aversion, crying), the generation of "blocked" emotions, alexithymia and awareness of emotions only at the level of sensations, rigidity of the emotional sphere, high level of work of such protective mechanisms as psychological displacement, negation, isolation of the affection.