Transient absorption study of two-photon excitation mechanism in the LH2 complex from purple bacterium Rhodobacter sphaeroides.

PubMed

Stepanenko, Ilya; Kompanetz, Viktor; Makhneva, Zoya; Chekalin, Sergey; Moskalenko, Andrei; Razjivin, Andrei

2012-03-08

The mechanism of two-photon excitation of a peripheral light-harvesting complex LH2 (B800-850) from purple bacterium Rhodobacter sphaeroides was explained on the basis of femtosecond transient absorption data. Fast bleaching of the B850 absorption band was measured under two-photon excitation by 1350 nm femtosecond pulses, showing fast subpicosecond arrival of excitation energy to B850 circular aggregates. Any spectral changes connected with the B800 absorption band of B800-BChl molecules were absent. A similar picture was observed under one-photon excitation of the LH2 complex by 675 nm femtosecond pulses. We believe these effects may be attributed to direct excitation of high-energy excitonic states of a B850 circular aggregate or its vibrational manifold in accordance with the model of Abe [Chem. Phys. 2001, 264, 355-363].

NMR of α-synuclein–polyamine complexes elucidates the mechanism and kinetics of induced aggregation

PubMed Central

Fernández, Claudio O; Hoyer, Wolfgang; Zweckstetter, Markus; Jares-Erijman, Elizabeth A; Subramaniam, Vinod; Griesinger, Christian; Jovin, Thomas M

2004-01-01

The aggregation of α-synuclein is characteristic of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. The 140-aa protein is natively unstructured; thus, ligands binding to the monomeric form are of therapeutic interest. Biogenic polyamines promote the aggregation of α-synuclein and may constitute endogenous agents modulating the pathogenesis of PD. We characterized the complexes of natural and synthetic polyamines with α-synuclein by NMR and assigned the binding site to C-terminal residues 109–140. Dissociation constants were derived from chemical shift perturbations. Greater polyamine charge (+2 → +5) correlated with increased affinity and enhancement of fibrillation, for which we propose a simple kinetic mechanism involving a dimeric nucleation center. According to the analysis, polyamines increase the extent of nucleation by ∼104 and the rate of monomer addition ∼40-fold. Significant secondary structure is not induced in monomeric α-synuclein by polyamines at 15°C. Instead, NMR reveals changes in a region (aa 22–93) far removed from the polyamine binding site and presumed to adopt the β-sheet conformation characteristic of fibrillar α-synuclein. We conclude that the C-terminal domain acts as a regulator of α-synuclein aggregation. PMID:15103328

Structural mechanisms of chaperone mediated protein disaggregation

PubMed Central

Sousa, Rui

2014-01-01

The ClpB/Hsp104 and Hsp70 classes of molecular chaperones use ATP hydrolysis to dissociate protein aggregates and complexes, and to move proteins through membranes. ClpB/Hsp104 are members of the AAA+ family of proteins which form ring-shaped hexamers. Loops lining the pore in the ring engage substrate proteins as extended polypeptides. Interdomain rotations and conformational changes in these loops coupled to ATP hydrolysis unfold and pull proteins through the pore. This provides a mechanism that progressively disrupts local secondary and tertiary structure in substrates, allowing these chaperones to dissociate stable aggregates such as β-sheet rich prions or coiled coil SNARE complexes. While the ClpB/Hsp104 mechanism appears to embody a true power-stroke in which an ATP powered conformational change in one protein is directly coupled to movement or structural change in another, the mechanism of force generation by Hsp70s is distinct and less well understood. Both active power-stroke and purely passive mechanisms in which Hsp70 captures spontaneous fluctuations in a substrate have been proposed, while a third proposed mechanism—entropic pulling—may be able to generate forces larger than seen in ATP-driven molecular motors without the conformational coupling required for a power-stroke. The disaggregase activity of these chaperones is required for thermotolerance, but unrestrained protein complex/aggregate dissociation is potentially detrimental. Disaggregating chaperones are strongly auto-repressed, and are regulated by co-chaperones which recruit them to protein substrates and activate the disaggregases via mechanisms involving either sequential transfer of substrate from one chaperone to another and/or simultaneous interaction of substrate with multiple chaperones. By effectively subjecting substrates to multiple levels of selection by multiple chaperones, this may insure that these potent disaggregases are only activated in the appropriate context. PMID:25988153

Structure and mechanics of aegagropilae fiber network.

PubMed

Verhille, Gautier; Moulinet, Sébastien; Vandenberghe, Nicolas; Adda-Bedia, Mokhtar; Le Gal, Patrice

2017-05-02

Fiber networks encompass a wide range of natural and manmade materials. The threads or filaments from which they are formed span a wide range of length scales: from nanometers, as in biological tissues and bundles of carbon nanotubes, to millimeters, as in paper and insulation materials. The mechanical and thermal behavior of these complex structures depends on both the individual response of the constituent fibers and the density and degree of entanglement of the network. A question of paramount importance is how to control the formation of a given fiber network to optimize a desired function. The study of fiber clustering of natural flocs could be useful for improving fabrication processes, such as in the paper and textile industries. Here, we use the example of aegagropilae that are the remains of a seagrass ( Posidonia oceanica ) found on Mediterranean beaches. First, we characterize different aspects of their structure and mechanical response, and second, we draw conclusions on their formation process. We show that these natural aggregates are formed in open sea by random aggregation and compaction of fibers held together by friction forces. Although formed in a natural environment, thus under relatively unconstrained conditions, the geometrical and mechanical properties of the resulting fiber aggregates are quite robust. This study opens perspectives for manufacturing complex fiber network materials.

Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

PubMed Central

Cotter, Christopher R.; Schüttler, Heinz-Bernd; Igoshin, Oleg A.; Shimkets, Lawrence J.

2017-01-01

Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, embryogenesis, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Known for its social developmental cycle, the bacterium Myxococcus xanthus uses coordinated movement to generate three-dimensional aggregates called fruiting bodies. Despite extensive progress in identifying genes controlling fruiting body development, cell behaviors and cell–cell communication mechanisms that mediate aggregation are largely unknown. We developed an approach to examine emergent behaviors that couples fluorescent cell tracking with data-driven models. A unique feature of this approach is the ability to identify cell behaviors affecting the observed aggregation dynamics without full knowledge of the underlying biological mechanisms. The fluorescent cell tracking revealed large deviations in the behavior of individual cells. Our modeling method indicated that decreased cell motility inside the aggregates, a biased walk toward aggregate centroids, and alignment among neighboring cells in a radial direction to the nearest aggregate are behaviors that enhance aggregation dynamics. Our modeling method also revealed that aggregation is generally robust to perturbations in these behaviors and identified possible compensatory mechanisms. The resulting approach of directly combining behavior quantification with data-driven simulations can be applied to more complex systems of collective cell movement without prior knowledge of the cellular machinery and behavioral cues. PMID:28533367

Aggregation behavior and complex structure between triblock copolymer and anionic surfactants

NASA Astrophysics Data System (ADS)

Li, Yiming; Bao, Mutai; Wang, Zhining; Zhang, Haixia; Xu, Guiying

2011-01-01

The aggregation behavior and complex structure of ABA triblock copolymer EO 76PO 30EO 76 (F68) with sodium dodecyl sulfate (SDS) and sodium bis(2-ethylhexyl)sulfonate (AOT) in aqueous solution were investigated by surface tension, fluorescence techniques and dynamic light-scattering (DLS) measurements. It is revealed that in certain regions of binding, surfactant/F68 complexes are formed. Structural informations and size of complexes are evaluated. When F68 is present in its nonassociated state, F68/micellar SDS complexes are formed at SDS concentrations above its critical aggregation concentration (cac). The cac is well below the critical micellar concentration (cmc) of pure SDS, and a model suggesting how complexes are formed at the cac in the presence of F68 is described. Experimental results show that SDS interacts with F68 mainly through hydrophobic forces, polypropylene oxide (PPO) groups of F68 are solubilized into SDS micellar cores and poly(ethylene oxide) (PEO) groups interact with SDS micelles. This interaction mechanism results in a "pearl-necklace" complex structure. However, a different structure occurs for F68/AOT complex at lower F68 concentrations, as nonassociated F68 interacts with AOT mainly through ion-dipole interactions. Complexes with a "wrapping" structure at lower F68 concentrations are formed.

Aggregate complexes of HIV-1 induced by multimeric antibodies.

PubMed

Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L; Robb, Merlin L; Kim, Jerome H; Denny, Thomas N; Tomaras, Georgia D; Shattock, Robin J

2014-10-02

Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

Model for fluorescence quenching in light harvesting complex II in different aggregation states.

PubMed

Andreeva, Atanaska; Abarova, Silvia; Stoitchkova, Katerina; Busheva, Mira

2009-02-01

Low-temperature (77 K) steady-state fluorescence emission spectroscopy and dynamic light scattering were applied to the main chlorophyll a/b protein light harvesting complex of photosystem II (LHC II) in different aggregation states to elucidate the mechanism of fluorescence quenching within LHC II oligomers. Evidences presented that LHC II oligomers are heterogeneous and consist of large and small particles with different fluorescence yield. At intermediate detergent concentrations the mean size of the small particles is similar to that of trimers, while the size of large particles is comparable to that of aggregated trimers without added detergent. It is suggested that in small particles and trimers the emitter is monomeric chlorophyll, whereas in large aggregates there is also another emitter, which is a poorly fluorescing chlorophyll associate. A model, describing populations of antenna chlorophyll molecules in small and large aggregates in their ground and first singlet excited states, is considered. The model enables us to obtain the ratio of the singlet excited-state lifetimes in small and large particles, the relative amount of chlorophyll molecules in large particles, and the amount of quenchers as a function of the degree of aggregation. These dependencies reveal that the quenching of the chl a fluorescence upon aggregation is due to the formation of large aggregates and the increasing of the amount of chlorophyll molecules forming these aggregates. As a consequence, the amount of quenchers, located in large aggregates, is increased, and their singlet excited-state lifetimes steeply decrease.

Mesoscale behavior study of collector aggregations in a wet dust scrubber.

PubMed

Li, Xiaochuan; Wu, Xiang; Hu, Haibin; Jiang, Shuguang; Wei, Tao; Wang, Dongxue

2018-01-01

In order to address the bottleneck problem of low fine-particle removal efficiency of self-excited dust scrubbers, this paper is focused on the influence of the intermittent gas-liquid two-phase flow on the mesoscale behavior of collector aggregations. The latter is investigated by the application of high-speed dynamic image technology to the self-excited dust scrubber experimental setup. The real-time-scale monitoring of the dust removal process is provided to clarify its operating mechanism at the mesoscale level. The results obtained show that particulate capturing in self-excited dust scrubber is provided by liquid droplets, liquid films/curtains, bubbles, and their aggregations. Complex spatial and temporal structures are intrinsic to each kind of collector morphology, and these are considered as the major factors controlling the dust removal mechanism of self-excited dust scrubbers. For the specific parameters of gas-liquid two-phase flow under study, the evolution patterns of particular collectors reflect the intrinsic, intermittent, and complex characteristics of the temporal structure. The intermittent initiation of the collector and the air hole formation-collapse cyclic processes provide time and space for the fine dust to escape from being trapped by the collectors. The above mesoscale experimental data provide more insight into the factors reducing the dust removal efficiency of self-excited dust scrubbers. This paper focuses on the reconsideration of the capturer aggregations of self-excited dust scrubbers from the mesoscale. Complex structures in time and space scales exist in each kind of capturer morphology. With changes of operating parameters, the morphology and spatial distributions of capturers diversely change. The change of the capturer over time presents remarkable, intermittent, and complex characteristics of the temporal structure.

Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy.

PubMed

Vasconcelos, Luís; Lehto, Tõnis; Madani, Fatemeh; Radoi, Vlad; Hällbrink, Mattias; Vukojević, Vladana; Langel, Ülo

2018-02-01

Peptides able to translocate cell membranes while carrying macromolecular cargo, as cell-penetrating peptides (CPPs), can contribute to the field of drug delivery by enabling the transport of otherwise membrane impermeable molecules. Formation of non-covalent complexes between amphipathic peptides and oligonucleotides is driven by electrostatic and hydrophobic interactions. Here we investigate and quantify the coexistence of distinct molecular species in multiple equilibria, namely peptide monomer, peptide self-aggregates and peptide/oligonucleotide complexes. As a model for the complexes, we used a stearylated peptide from the PepFect family, PF14 and siRNA. PF14 has a cationic part and a lipid part, resembling some characteristics of cationic lipids. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) were used to detect distinct molecular entities in solution and at the plasma membrane of live cells. For that, we labeled the peptide with carboxyrhodamine 6G and the siRNA with Cyanine 5. We were able to detect fluorescent entities with diffusional properties characteristic of the peptide monomer as well as of peptide aggregates and peptide/oligonucleotide complexes. Strategies to avoid peptide adsorption to solid surfaces and self-aggregation were developed and allowed successful FCS measurements in solution and at the plasma membrane. The ratio between the detected molecular species was found to vary with pH, peptide concentration and the proximity to the plasma membrane. The present results suggest that the diverse cellular uptake mechanisms, often reported for amphipathic CPPs, might result from the synergistic effect of peptide monomers, self-aggregates and cargo complexes, distributed unevenly at the plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

Complexation of amyloid fibrils with charged conjugated polymers.

PubMed

Ghosh, Dhiman; Dutta, Paulami; Chakraborty, Chanchal; Singh, Pradeep K; Anoop, A; Jha, Narendra Nath; Jacob, Reeba S; Mondal, Mrityunjoy; Mankar, Shruti; Das, Subhadeep; Malik, Sudip; Maji, Samir K

2014-04-08

It has been suggested that conjugated charged polymers are amyloid imaging agents and promising therapeutic candidates for neurological disorders. However, very less is known about their efficacy in modulating the amyloid aggregation pathway. Here, we studied the modulation of Parkinson's disease associated α-synuclein (AS) amyloid assembly kinetics using conjugated polyfluorene polymers (PF, cationic; PFS, anionic). We also explored the complexation of these charged polymers with the various AS aggregated species including amyloid fibrils and oligomers using multidisciplinary biophysical techniques. Our data suggests that both polymers irrespective of their different charges in the side chains increase the fibrilization kinetics of AS and also remarkably change the morphology of the resultant amyloid fibrils. Both polymers were incorporated/aligned onto the AS amyloid fibrils as evident from electron microscopy (EM) and atomic force microscopy (AFM), and the resultant complexes were structurally distinct from their pristine form of both polymers and AS supported by FTIR study. Additionally, we observed that the mechanism of interactions between the polymers with different species of AS aggregates were markedly different.

Freeze/thaw stress induces organelle remodeling and membrane recycling in cryopreserved human mature oocytes.

PubMed

Nottola, Stefania Annarita; Albani, Elena; Coticchio, Giovanni; Palmerini, Maria Grazia; Lorenzo, Caterina; Scaravelli, Giulia; Borini, Andrea; Levi-Setti, Paolo Emanuele; Macchiarelli, Guido

2016-12-01

Our aim was to evaluate the ultrastructure of human metaphase II oocytes subjected to slow freezing and fixed after thawing at different intervals during post-thaw rehydration. Samples were studied by light and transmission electron microscopy. We found that vacuolization was present in all cryopreserved oocytes, reaching a maximum in the intermediate stage of rehydration. Mitochondria-smooth endoplasmic reticulum (M-SER) aggregates decreased following thawing, particularly in the first and intermediate stages of rehydration, whereas mitochondria-vesicle (MV) complexes augmented in the same stages. At the end of rehydration, vacuoles and MV complexes both diminished and M-SER aggregates increased again. Cortical granules (CGs) were scarce in all cryopreserved oocytes, gradually diminishing as rehydration progressed. This study also shows that such a membrane remodeling is mainly represented by a dynamic process of transition between M-SER aggregates and MV complexes, both able of transforming into each other. Vacuoles and CG membranes may take part in the membrane recycling mechanism.

Influence of detergent concentration on aggregation and spectroscopic properties of light-harvesting complex II.

PubMed

Voigt, Bernd; Krikunova, Maria; Lokstein, Heiko

2008-01-01

Aggregation of photosynthetic light-harvesting complexes strongly influences their spectroscopic properties. Fluorescence yield and excited state lifetimes of the main light-harvesting complex (LHC II) of higher plants strongly depend on its aggregation state. Detergents are commonly used to solubilize membrane proteins and/or to circumvent their aggregation in aqueous environments. Nonlinear polarization spectroscopy in the frequency domain (NLPF) was performed with LHC II over a wide concentration range of the mild detergent n-dodecyl beta-D: -maltoside (beta-DM). Additionally, conventional absorption-, fluorescence- and circular dichroism-spectra were measured.The results indicate that: (i) conventional spectroscopic techniques are not well suited to investigate aggregation effects. NLPF provides a novel approach to overcome this problem: NLPF spectra display dramatic alterations upon even minor beta-DM concentration changes. (ii) Commonly used detergent concentrations (around or slightly above the critical micellar concentration) apparently do not lead to complete trimerization of LHC II. A long-wavelength species in the NLPF spectra (peaking at about 685 nm), indicative of residual aggregation, persists up to DM-concentrations of 0.06%. (iii) High-resolution NLPF spectra indicate the existence of a species with a considerably shortened excited state lifetime. (iv) No indication of denaturation was found even at the highest beta-DM concentrations used. (v) A specific change in interaction between certain chlorophyll(s) b and a xanthophyll molecule, probably neoxanthin, was detected upon aggregation as well as at higher beta-DM concentrations. The results are discussed with respect to the still elusive mechanism of nonradiative dissipation of excess excitation energy in the antenna system.

The Role of Shape Complementarity in the Protein-Protein Interactions

PubMed Central

Li, Ye; Zhang, Xianren; Cao, Dapeng

2013-01-01

We use a dissipative particle dynamic simulation to investigate the effects of shape complementarity on the protein-protein interactions. By monitoring different kinds of protein shape-complementarity modes, we gave a clear mechanism to reveal the role of the shape complementarity in the protein-protein interactions, i.e., when the two proteins with shape complementarity approach each other, the conformation of lipid chains between two proteins would be restricted significantly. The lipid molecules tend to leave the gap formed by two proteins to maximize the configuration entropy, and therefore yield an effective entropy-induced protein-protein attraction, which enhances the protein aggregation. In short, this work provides an insight into understanding the importance of the shape complementarity in the protein-protein interactions especially for protein aggregation and antibody–antigen complexes. Definitely, the shape complementarity is the third key factor affecting protein aggregation and complex, besides the electrostatic-complementarity and hydrophobic complementarity. PMID:24253561

The Role of Shape Complementarity in the Protein-Protein Interactions

NASA Astrophysics Data System (ADS)

Li, Ye; Zhang, Xianren; Cao, Dapeng

2013-11-01

We use a dissipative particle dynamic simulation to investigate the effects of shape complementarity on the protein-protein interactions. By monitoring different kinds of protein shape-complementarity modes, we gave a clear mechanism to reveal the role of the shape complementarity in the protein-protein interactions, i.e., when the two proteins with shape complementarity approach each other, the conformation of lipid chains between two proteins would be restricted significantly. The lipid molecules tend to leave the gap formed by two proteins to maximize the configuration entropy, and therefore yield an effective entropy-induced protein-protein attraction, which enhances the protein aggregation. In short, this work provides an insight into understanding the importance of the shape complementarity in the protein-protein interactions especially for protein aggregation and antibody-antigen complexes. Definitely, the shape complementarity is the third key factor affecting protein aggregation and complex, besides the electrostatic-complementarity and hydrophobic complementarity.

Characterizing the mechanical behavior of the zebrafish germ layers

NASA Astrophysics Data System (ADS)

Kealhofer, David; Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Lucio, Adam; Campàs, Otger

Organ morphogenesis and the development of the animal body plan involve complex spatial and temporal control of tissue- and cell-level mechanics. A prime example is the generation of stresses by individual cells to reorganize the tissue. These processes have remained poorly understood due to a lack of techniques to characterize the local constitutive law of the material, which relates local cellular forces to the resulting tissue flows. We have developed a method for quantitative, local in vivo study of material properties in living tissue using magnetic droplet probes. We use this technique to study the material properties of the different zebrafish germ layers using aggregates of zebrafish mesendodermal and ectodermal cells as a model system. These aggregates are ideal for controlled studies of the mechanics of individual germ layers because of the homogeneity of the cell type and the simple spherical geometry. Furthermore, the numerous molecular tools and transgenic lines already developed for this model organism can be applied to these aggregates, allowing us to characterize the contributions of cell cortex tension and cell adhesion to the mechanical properties of the zebrafish germ layers.

Interactions between extracellular polymeric substances and clay minerals affect soil aggregation

NASA Astrophysics Data System (ADS)

Vogel, Cordula; Rehschuh, Stephanie; Kemi Olagoke, Folasade; Redmile Gordon, Marc; Kalbiltz, Karsten

2017-04-01

Soil aggregation is crucial for carbon (C) sequestration and microbial processes have been recognised as important control of aggregate turnover (formation, stability, and destruction). However, how microorganisms contribute to these processes is still a matter of debate. An enthralling mechanism determining aggregate turnover and therefore C sequestration may be the excretion of extracellular polymeric substances (EPS) as microbial glue, but effects of EPS on aggregation is largely unknown. Moreover, interdependencies between important aggregation factors like the amount of fine-sized particles (clay content), the decomposability of organic matter and the microbial community (size and composition, as well as the excretion of EPS) are still poorly understood. Therefore, we studied the complex interactions between these factors and their role in aggregate turnover. It was hypothesized that an increase in microbial activity, induced by the input of organic substrates, will stimulate EPS production and therefore the formation and stability of aggregates. To test this hypothesis, an incubation experiment has been conducted across a gradient of clay content (montmorillonite) and substrate decomposability (starch and glucose) as main drivers of the microbial activity. A combination of aggregate separation and stability tests were applied. This results will be examined with respect to the obtained microbial parameters (amount and composition of EPS, CO2 emission, microbial biomass, phospholipid fatty acid), to disentangle the mechanisms and factors controlling aggregate turnover affected by soil microorganisms. This study is expected to provide insights on the role of EPS in the stability of aggregates. Thus, the results of this study will provide an improved understanding of the underlying processes of aggregate turnover in soils, which is necessary to implement strategies for enhanced C sequestration in agricultural soils.

An insight into the complex prion-prion interaction network in the budding yeast Saccharomyces cerevisiae.

PubMed

Du, Zhiqiang; Valtierra, Stephanie; Li, Liming

2014-01-01

The budding yeast Saccharomyces cerevisiae is a valuable model system for studying prion-prion interactions as it contains multiple prion proteins. A recent study from our laboratory showed that the existence of Swi1 prion ([SWI(+)]) and overproduction of Swi1 can have strong impacts on the formation of 2 other extensively studied yeast prions, [PSI(+)] and [PIN(+)] ([RNQ(+)]) (Genetics, Vol. 197, 685-700). We showed that a single yeast cell is capable of harboring at least 3 heterologous prion elements and these prions can influence each other's appearance positively and/or negatively. We also showed that during the de novo [PSI(+)] formation process upon Sup35 overproduction, the aggregation patterns of a preexisting inducer ([RNQ(+)] or [SWI(+)]) can undergo significant remodeling from stably transmitted dot-shaped aggregates to aggregates that co-localize with the newly formed Sup35 aggregates that are ring/ribbon/rod- shaped. Such co-localization disappears once the newly formed [PSI(+)] prion stabilizes. Our finding provides strong evidence supporting the "cross-seeding" model for prion-prion interactions and confirms earlier reports that the interactions among different prions and their prion proteins mostly occur at the initiation stages of prionogenesis. Our results also highlight a complex prion interaction network in yeast. We believe that elucidating the mechanism underlying the yeast prion-prion interaction network will not only provide insight into the process of prion de novo generation and propagation in yeast but also shed light on the mechanisms that govern protein misfolding, aggregation, and amyloidogenesis in higher eukaryotes.

Chaperone-client complexes: A dynamic liaison

NASA Astrophysics Data System (ADS)

Hiller, Sebastian; Burmann, Björn M.

2018-04-01

Living cells contain molecular chaperones that are organized in intricate networks to surveil protein homeostasis by avoiding polypeptide misfolding, aggregation, and the generation of toxic species. In addition, cellular chaperones also fulfill a multitude of alternative functionalities: transport of clients towards a target location, help them fold, unfold misfolded species, resolve aggregates, or deliver clients towards proteolysis machineries. Until recently, the only available source of atomic resolution information for virtually all chaperones were crystal structures of their client-free, apo-forms. These structures were unable to explain details of the functional mechanisms underlying chaperone-client interactions. The difficulties to crystallize chaperones in complexes with clients arise from their highly dynamic nature, making solution NMR spectroscopy the method of choice for their study. With the advent of advanced solution NMR techniques, in the past few years a substantial number of structural and functional studies on chaperone-client complexes have been resolved, allowing unique insight into the chaperone-client interaction. This review summarizes the recent insights provided by advanced high-resolution NMR-spectroscopy to understand chaperone-client interaction mechanisms at the atomic scale.

Concepts and tools to exploit the potential of bacterial inclusion bodies in protein science and biotechnology.

PubMed

Gatti-Lafranconi, Pietro; Natalello, Antonino; Ami, Diletta; Doglia, Silvia Maria; Lotti, Marina

2011-07-01

Cells have evolved complex and overlapping mechanisms to protect their proteins from aggregation. However, several reasons can cause the failure of such defences, among them mutations, stress conditions and high rates of protein synthesis, all common consequences of heterologous protein production. As a result, in the bacterial cytoplasm several recombinant proteins aggregate as insoluble inclusion bodies. The recent discovery that aggregated proteins can retain native-like conformation and biological activity has opened the way for a dramatic change in the means by which intracellular aggregation is approached and exploited. This paper summarizes recent studies towards the direct use of inclusion bodies in biotechnology and for the detection of bottlenecks in the folding pathways of specific proteins. We also review the major biophysical methods available for revealing fine structural details of aggregated proteins and which information can be obtained through these techniques. © 2011 The Authors Journal compilation © 2011 FEBS.

Structural elucidation of the interaction between neurodegenerative disease-related tau protein with model lipid membranes

NASA Astrophysics Data System (ADS)

Jones, Emmalee M.

A protein's sequence of amino acids determines how it folds. That folded structure is linked to protein function, and misfolding to dysfunction. Protein misfolding and aggregation into beta-sheet rich fibrillar aggregates is connected with over 20 neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized in part by misfolding, aggregation and deposition of the microtubule associated tau protein into neurofibrillary tangles (NFTs). However, two questions remain: What is tau's fibrillization mechanism, and what is tau's cytotoxicity mechanism? Tau is prone to heterogeneous interactions, including with lipid membranes. Lipids have been found in NFTs, anionic lipid vesicles induced aggregation of the microtubule binding domain of tau, and other protein aggregates induced ion permeability in cells. This evidence prompted our investigation of tau's interaction with model lipid membranes to elucidate the structural perturbations those interactions induced in tau protein and in the membrane. We show that although tau is highly charged and soluble, it is highly surface active and preferentially interacts with anionic membranes. To resolve molecular-scale structural details of tau and model membranes, we utilized X-ray and neutron scattering techniques. X-ray reflectivity indicated tau aggregated at air/water and anionic lipid membrane interfaces and penetrated into membranes. More significantly, membrane interfaces induced tau protein to partially adopt a more compact conformation with density similar to folded protein and ordered structure characteristic of beta-sheet formation. This suggests possible membrane-based mechanisms of tau aggregation. Membrane morphological changes were seen using fluorescence microscopy, and X-ray scattering techniques showed tau completely disrupts anionic membranes, suggesting an aggregate-based cytotoxicity mechanism. Further investigation of protein constructs and a "hyperphosphorylation" disease mimic helped clarify the role of the microtubule binding domain in anionic lipid affinity and demonstrated even "hyperphosphorylation" did not prevent interaction with anionic membranes. Additional studies investigated more complex membrane models to increase physiological relevance. These insights revealed structural changes in tau protein and lipid membranes after interaction. We observed tau's affinity for interfaces, and aggregation and compaction once tau partitions to interfaces. We observed the beginnings of beta-sheet formation in tau at anionic lipid membranes. We also examined disruption to the membrane on a molecular scale.

(E)-4-Methyl-N-((quinolin-2-yl)ethylidene)aniline as ligand for IIB supramolecular complexes: synthesis, structure, aggregation-induced emission enhancement and application in PMMA-doped hybrid material.

PubMed

Wang, Ani; Fan, Ruiqing; Dong, Yuwei; Chen, Wei; Song, Yang; Wang, Ping; Hao, Sue; Liu, Zhigang; Yang, Yulin

2016-12-20

Judicious structural design employing 2-quinolinecarboxaldehyde and 4-methylaniline was used to generate the Schiff base ligand (E)-4-methyl-N-((quinolin-2-yl)ethylidene)aniline (L). Five IIB complexes, namely, [ZnLCl 2 ] (1), [ZnL(NO 3 ) 2 ] (2), [ZnL(OAc) 2 ] 3 (3), [CdL(OAc) 2 ] 3 (4), and [HgLCl 2 ] (5) have been synthesized based on L. Single-crystal X-ray diffraction analysis indicates that complexes 1, 3 and 4 exhibit 3D networks, whereas 2 and 5 form 2D layers and 1D chains, respectively. TD-DFT calculations show a good correlation with the UV-vis absorption assigned to π → π* intraligand transitions. Furthermore, complexes 1-5 displayed strong greenish luminescent emissions (518-524 nm) in the aggregate state but weak emissions in solution (aggregation-induced emission enhancement), which may be due to the existence of C-HCl/O hydrogen bonding and ππ stacking interactions, resulting in restriction of intramolecular rotation (RIR). Variable-concentration 1 H NMR studies suggested that the aggregates undergo intramolecular changes in conformation due to intermolecular interactions. Moreover, the emission intensity and lifetime exhibited obvious increases induced by mechanical grinding and temperature reduction, which were also attributed to AIEE properties. Subsequently, complex 1 was incorporated into poly(methyl methacrylate) (PMMA), whereby 1-PMMA exhibited enhanced emission intensity (20-fold increase in comparison with that of 1), which offers opportunities for use in plastic greenhouses to increase leaf photosynthesis.

Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces.

PubMed

Chouchane, Karim; Vendrely, Charlotte; Amari, Myriam; Moreaux, Katie; Bruckert, Franz; Weidenhaupt, Marianne

2015-08-20

Soluble proteins are constantly in contact with material or cellular surfaces, which can trigger their aggregation and therefore have a serious impact on the development of stable therapeutic proteins. In contact with hydrophobic material surfaces, human insulin aggregates readily into amyloid fibers. The kinetics of this aggregation can be accelerated by small peptides, forming stable beta-sheets on hydrophobic surfaces. Using a series of (LK)nL peptides with varying length, we show that these peptides, at low, substoichiometric concentrations, have a positive, cooperative effect on insulin aggregation. This effect is based on a cooperative adsorption of (LK)nL peptides at hydrophobic surfaces, where they form complexes that help the formation of aggregation nuclei. At higher concentrations, they interfere with the formation of an aggregative nucleus. These effects are strictly dependent on the their adsorption on hydrophobic material surfaces and highlight the importance of the impact of materials on protein stability. (LK)nL peptides prove to be valuable tools to investigate the mechanism of HI aggregation nuclei formation on hydrophobic surfaces.

Molecular design of boronic acid-functionalized squarylium cyanine dyes for multiple discriminant analysis of sialic acid in biological samples: selectivity toward monosaccharides controlled by different alkyl side chain lengths.

PubMed

Ouchi, Kazuki; Colyer, Christa L; Sebaiy, Mahmoud; Zhou, Jin; Maeda, Takeshi; Nakazumi, Hiroyuki; Shibukawa, Masami; Saito, Shingo

2015-02-03

We designed a new series of boronic acid-functionalized squarylium cyanine dyes (SQ-BA) with different lengths of alkyl chain residues, suitable for multiple discriminant analysis (MDA) of sialic acid (Neu5Ac) in biological samples. The SQ-BA dyes form aggregates based on hydrophobic interactions, which result in quenched fluorescence in aqueous solutions. When the boronic acid binds with saccharides, the fluorescence intensity increases as a result of dissociation to the emissive monomeric complex. We inferred that different dye aggregate structures (H-aggregates and J-aggregates) were induced depending on the alkyl chain length, so that monosaccharides would be recognized in different ways (especially, multipoint interaction with J-aggregates). A distinctive emission enhancement of SQ-BA dyes with shorter-alkyl-chains in the presence of Neu5Ac was observed (2.4-fold fluorescence enhancement; with formation constant 10(1.7) M(-1)), with no such enhancement for SQ-BA dyes with longer-alkyl-chain. In addition, various enhancement factors for other monosaccharides were observed depending on the alkyl chain length. Detailed thermodynamic and NMR studies of the SQ-BA complexes revealed the unique recognition mechanism: the dye aggregate with a shorter-alkyl-chain causes the slipped parallel structure and forms a stable 2:1 complex with Neu5Ac, as distinct from longer-alkyl-chain dyes, which form a 1:1 monomeric complex. MDA using the four SQ-BA dyes was performed for human urine samples, resulting in the successful discrimination between normal and abnormal Neu5Ac levels characteristic of disease. Thus, we successfully controlled various responses to similar monosaccharides with a novel approach that chemically modified not the boronic acid moiety itself but the length of the alkyl chain residue attached to the dye in order to generate specificity.

Early Events in Insulin Fibrillization Studied by Time-Lapse Atomic Force Microscopy

PubMed Central

Podestà, Alessandro; Tiana, Guido; Milani, Paolo; Manno, Mauro

2006-01-01

The importance of understanding the mechanism of protein aggregation into insoluble amyloid fibrils lies not only in its medical consequences, but also in its more basic properties of self-organization. The discovery that a large number of uncorrelated proteins can form, under proper conditions, structurally similar fibrils has suggested that the underlying mechanism is a general feature of polypeptide chains. In this work, we address the early events preceding amyloid fibril formation in solutions of zinc-free human insulin incubated at low pH and high temperature. Here, we show by time-lapse atomic force microscopy that a steady-state distribution of protein oligomers with a quasiexponential tail is reached within a few minutes after heating. This metastable phase lasts for a few hours, until fibrillar aggregates are observable. Although for such complex systems different aggregation mechanisms can occur simultaneously, our results indicate that the prefibrillar phase is mainly controlled by a simple coagulation-evaporation kinetic mechanism, in which concentration acts as a critical parameter. These experimental facts, along with the kinetic model used, suggest a critical role for thermal concentration fluctuations in the process of fibril nucleation. PMID:16239333

Computational Study of the Aza-Michael Addition of the Flavonoid (+)-Taxifolin in the Inhibition of β-Amyloid Fibril Aggregation.

PubMed

Ginex, Tiziana; Trius, Marta; Luque, F Javier

2018-04-17

Inhibition of abnormal protein self-aggregation is an attractive strategy against amyloidogenic diseases, but has found limited success due to the complexity of protein self-assembly, the absence of fully reproducible aggregation assays, and the scarce knowledge of the inhibition mechanisms by small molecules. In this context, catechol-containing compounds may lead to covalent adducts with amyloid fibrils that interfere with the aggregation process. In particular, the covalent adduct formed between the oxidized form of (+)-taxifolin and an β-amyloid (Aβ42) suggests the involvement of a specific recognition motif that enables the chemical reaction with Aβ42. In this study, we have examined the mechanisms implicated in the aza-Michael addition of the o-quinone species of (+)-taxifolin with Aβ42 fibrils. The results support the binding of (+)-taxifolin to the hydrophobic groove delimited by the edges defined by Lys16 and Glu22 residues in the fibril. The chemical reaction proceeds through the nucleophilic attack of the deprotonated amino group of a Lys16 residue in a process activated by the interaction between the o-quinone ring with a vicinal Lys16 residue, as well as by a water-assisted proton transfer, which is the rate-limiting step of the reaction. This specific inhibition mechanism, which may explain the enhanced anti-aggregating activity of oxidized flavonoids compared to fresh compounds, holds promise for developing disease-modifying therapies. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of Pedogenic Fe Oxides on Soil Aggregate-Associated Carbon

NASA Astrophysics Data System (ADS)

Asefaw Berhe, A.; Jin, L.

2017-12-01

Carbon sequestration is intimately related to the soil structure, mainly soil aggregate dynamics. Carbon storage in soil aggregates has been recognized as an important carbon stabilization mechanism in soils. Organic matter and pedogenic Fe oxides are major binding agents that facilitate soil aggregate formation and stability. However, few studies have investigated how different forms of pedogenic Fe oxides can affect soil carbon distribution in different aggregate-size fractions. We investigated sequentially extracted pedogenic Fe oxides (in the order of organically complexed Fe extracted with sodium pyrophosphate, poorly-crystalline Fe oxides extracted with hydroxylamine hydrochloride, and crystalline Fe oxides extracted with dithionite hydrochloride) and determined the amount and nature of C in macroaggregates (2-0.25mm), microaggregates (0.25-0.053mm), and two silt and clay fractions (0.053-0.02mm, and <0.02mm) in Musick soil from Sierra Nevada mountain in California. We also determined how pedogenic Fe oxides affect soil carbon distribution along soil depth gradients. Findings of our study revealed that the proportion of organic matter complexed Fe decreased, but the proportion of crystalline Fe increased with increasing soil depths. Poorly crystalline Fe oxides (e.g. ferrihydrite) was identified as a major Fe oxide in surface soil, whereas crystalline Fe oxides (e.g. goethite) were found in deeper soil layers. These results suggest that high concentration of organic matter in surface soil suppressed Fe crystallization. Calcium cation was closely related to the pyrophosphate extractable Fe and C, which indicates that calcium may be a major cation that contribute to the organic matter complexed Fe and C pool. Increasing concentrations of extractable Fe and C with decreasing aggregate size fractions also suggests that Fe oxides play an important role in formation and stability of silt and clay fractions, and leading to further stabilization of carbon in soil. Our findings provide mechanistic understanding of how pedogenic Fe oxides play important role in carbon stabilization in different aggregate-size fractions in soil.

Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity.

PubMed

Malina, Jaroslav; Farrell, Nicholas P; Brabec, Viktor

2014-11-17

The trinuclear platinum complexes (TriplatinNC-A [{Pt(NH3 )3 }2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](6+) , and TriplatinNC [{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH3 (+) )}2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](8+) ) are biologically active agents that bind to DNA through noncovalent (hydrogen bonding, electrostatic) interactions. Herein, we show that TriplatinNC condenses DNA with a much higher potency than conventional DNA condensing agents. Both complexes induce aggregation of small transfer RNA molecules, and TriplatinNC in particular completely inhibits DNA transcription at lower concentrations than naturally occurring spermine. Topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at concentrations which were 60 times and 250 times lower than that of spermine. The mechanisms for the biological activity of TriplatinNC-A and TriplatinNC may be associated with their ability to condense/aggregate nucleic acids with consequent inhibitory effects on crucial enzymatic activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fractality à la carte: a general particle aggregation model.

PubMed

Nicolás-Carlock, J R; Carrillo-Estrada, J L; Dossetti, V

2016-01-19

In nature, fractal structures emerge in a wide variety of systems as a local optimization of entropic and energetic distributions. The fractality of these systems determines many of their physical, chemical and/or biological properties. Thus, to comprehend the mechanisms that originate and control the fractality is highly relevant in many areas of science and technology. In studying clusters grown by aggregation phenomena, simple models have contributed to unveil some of the basic elements that give origin to fractality, however, the specific contribution from each of these elements to fractality has remained hidden in the complex dynamics. Here, we propose a simple and versatile model of particle aggregation that is, on the one hand, able to reveal the specific entropic and energetic contributions to the clusters' fractality and morphology, and, on the other, capable to generate an ample assortment of rich natural-looking aggregates with any prescribed fractal dimension.

Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

NASA Astrophysics Data System (ADS)

Pineda, M.; Eftimie, R.

2017-12-01

The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

Aggregation landscapes of Huntingtin exon 1 protein fragments and the critical repeat length for the onset of Huntington’s disease

PubMed Central

Chen, Mingchen; Wolynes, Peter G.

2017-01-01

Huntington’s disease (HD) is a neurodegenerative disease caused by an abnormal expansion in the polyglutamine (polyQ) track of the Huntingtin (HTT) protein. The severity of the disease depends on the polyQ repeat length, arising only in patients with proteins having 36 repeats or more. Previous studies have shown that the aggregation of N-terminal fragments (encoded by HTT exon 1) underlies the disease pathology in mouse models and that the HTT exon 1 gene product can self-assemble into amyloid structures. Here, we provide detailed structural mechanisms for aggregation of several protein fragments encoded by HTT exon 1 by using the associative memory, water-mediated, structure and energy model (AWSEM) to construct their free energy landscapes. We find that the addition of the N-terminal 17-residue sequence (NT17) facilitates polyQ aggregation by encouraging the formation of prefibrillar oligomers, whereas adding the C-terminal polyproline sequence (P10) inhibits aggregation. The combination of both terminal additions in HTT exon 1 fragment leads to a complex aggregation mechanism with a basic core that resembles that found for the aggregation of pure polyQ repeats using AWSEM. At the extrapolated physiological concentration, although the grand canonical free energy profiles are uphill for HTT exon 1 fragments having 20 or 30 glutamines, the aggregation landscape for fragments with 40 repeats has become downhill. This computational prediction agrees with the critical length found for the onset of HD and suggests potential therapies based on blocking early binding events involving the terminal additions to the polyQ repeats. PMID:28400517

The role of wine polysaccharides on salivary protein-tannin interaction: A molecular approach.

PubMed

Brandão, Elsa; Silva, Mafalda Santos; García-Estévez, Ignacio; Williams, Pascale; Mateus, Nuno; Doco, Thierry; de Freitas, Victor; Soares, Susana

2017-12-01

Polysaccharides are described to inhibit aggregation between food polyphenols and salivary proteins (SP) and may hence lead to astringency modulation. In this work, the effect of two wine polysaccharides (arabinogalactan proteins-AGPs and rhamnogalacturonan II- RGII) on SP-polyphenol interaction was evaluated. In general, both polysaccharides were effective to inhibit or reduce SP-polyphenol interaction and aggregation. They can act by two different mechanisms (ternary or competitive) depending on the SP-tannin pair. In the case of salivary P-B peptide, AGPs and RGII seem to act by a ternary mechanism, in which they surround this complex, enhancing its solubility. Concerning acidic proline-rich proteins (aPRPs), it was possible to observe both mechanisms, depending on the tannin and the polysaccharide involved. Overall, this work point out for a specific property of wine polysaccharides important to modulate this and other beverages and food astringency perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Property Morphology Correlations of Organic Semiconductor Nanowires

NASA Astrophysics Data System (ADS)

McFarland, Frederick Marshall

Chemically doped and non-doped P3HT nanoaggregates are studied to establish a comprehensive understanding of the interplay between their morphology and various optoelectronic properties. One-dimensional nanoaggregates of P3HT are chosen as the model systems here due to their high surface/volume ratio and suitability for microscopic investigations. Atomic force microscopy (AFM) and kelvin probe force microscopy (KPFM) are used to correlate property/morphology characteristics of non-doped P3HT nanowhiskers. Topographical measurements indicate that individually folded P3HT motifs stack via interfacial interactions to form nanowhiskers in solution. Further aging leads to multi-layered nanowhiskers with greater stability and less instances of ?-? sliding of interfacial edge-on oriented motifs. KPFM measurements show higher surface potentials on portions of nanowhiskers containing local defects and stacking faults due to overlapping, and nanowhiskers that are at least triple-layered. Simultaneous UV-Vis and AFM characterizations compare the aggregation rates and morphologies of doped and non-doped P3HT nanowhiskers. Allowing fully solubilized P3HT to age without doping may produce high aspect ratio nanowhiskers containing disordered segments protruding out from the edges of the nanowhiskers. These protruding segments could also serve as "tie-molecules" between adjacent nanowhiskers. Doping fully solubilized P3HT will lead to substantially higher rates of P3HT aggregation. Doped nanowhiskers also display different morphologies. They pack tighter, are smoother, and are thicker and higher versus non-doped nanowhiskers, indicating a different aggregation mechanism. Stopped flow-kinetics was employed to investigate the reactivity of two distinctively different morphological forms of P3HT towards dopants. Fully solubilized P3HT undergoes a slow doping mechanism whereas pre-aggregated P3HT undergoes a fast doping mechanism. Pseudo-single reactant rate fittings indicate that both mechanisms appear to be 1st order in P3HT, whereby pre-aggregated P3HT mixtures will produce more doped products per P3HT monomer unit than fully solubilized P3HT. This study highlights the impact of conjugated polymer's morphology on their doping efficiency. Density functional theory was used to investigate the charge transfer (CT) states between oligothiophene and F4-TCNQ. CT of several unreported complexes that feature two oligomers stacked in a sandwich or layered configuration is investigated. Our preliminary results suggest that these new complexes can generate substantially more charge per F4-TCNQ than previously reported.

Cytosolic Proteostasis via Importing of Misfolded Proteins into Mitochondria

PubMed Central

Ruan, Linhao; Zhou, Chuankai; Jin, Erli; Kucharavy, Andrei; Zhang, Ying; Wen, Zhihui; Florens, Laurence; Li, Rong

2017-01-01

Loss of proteostasis underlies aging and neurodegeneration characterized by the accumulation of protein aggregates and mitochondrial dysfunction1–5. Although many neurodegenerative-disease proteins can be found in mitochondria4,6, it remains unclear how these disease manifestations may be related. In yeast, protein aggregates formed under stress or during aging are preferentially retained by the mother cell in part through tethering to mitochondria, while the disaggregase Hsp104 helps dissociate aggregates to enable refolding or degradation of misfolded proteins7–10. Here we show that in yeast cytosolic proteins prone to aggregation are imported into mitochondria for degradation. Protein aggregates formed under heat shock (HS) contain both cytosolic and mitochondrial proteins and interact with mitochondrial import complex. Many aggregation-prone proteins enter mitochondrial intermembrane space and matrix after HS, while some do so even without stress. Timely dissolution of cytosolic aggregates requires mitochondrial import machinery and proteases. Blocking mitochondrial import but not the proteasome activity causes a marked delay in the degradation of aggregated proteins. Defects in cytosolic Hsp70s leads to enhanced entry of misfolded proteins into mitochondria and elevated mitochondrial stress. We term this mitochondria-mediated proteostasis mechanism MAGIC (mitochondria as guardian in cytosol) and provide evidence that it may exist in human cells. PMID:28241148

Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

NASA Astrophysics Data System (ADS)

Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

2012-09-01

Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

Changes in the energy distribution between chlorophyll-protein complexes of thylakoid membranes from pea mutants with modified pigment content. I. Changes due to the modified pigment content.

PubMed

Andreeva, Atanaska; Stoitchkova, Katerina; Busheva, Mira; Apostolova, Emilia

2003-07-01

The low-temperature (77 K) emission and excitation chlorophyll fluorescence spectra in thylakoid membranes isolated from pea mutants were investigated. The mutants have modified pigment content, structural organization, different surface electric properties and functions [Dobrikova et al., Photosynth. Res. 65 (2000) 165]. The emission spectra of thylakoid membranes were decomposed into bands belonging to the main pigment protein complexes. By an integration of the areas under them, the changes in the energy distribution between the two photosystems as well as within each one of them were estimated. It was shown that the excitation energy flow to the light harvesting, core antenna and RC complexes of photosystem II increases with the total amount of pigments in the mutants, relative to the that to photosystem I complexes. A reduction of the fluorescence ratio between aggregated trimers of LHC II and its trimeric and monomeric forms with the increase of the pigment content (chlorophyll a, chlorophyll b, and lutein) was observed. This implies that the closer packing in the complexes with a higher extent of aggregation regulates the energy distribution to the PS II core antenna and reaction centers complexes. Based on the reduced energy flow to PS II, i.e., the relative increased energy flow to PS I, we hypothesize that aggregation of LHC II switches the energy flow toward LHC I. These results suggest an additive regulatory mechanism, which redistributes the excitation energy between the two photosystems and operates at non-excess light intensities but at reduced pigment content.

Light harvesting control in plants.

PubMed

Ruban, Alexander V

2018-05-23

In 1991, my colleagues and I published a hypothesis article that proposed a mechanism that controls light harvesting in plants and protects them against photodamage. The major light harvesting complex, LHCII, was suggested to undergo aggregation upon exposure of the plant to damaging levels of light. Aggregated LHCII was found to be much less efficient in light harvesting, as it promptly dissipated absorbed energy into heat, possessing a very low chlorophyll fluorescence yield. Non-photochemical quenching (NPQ) is a term coined to describe this reduction in chlorophyll fluorescence yield. This article is a story of how the hypothesis that LHCII aggregation is involved in NPQ is developed into a model that is now becoming broadly accepted by the research community. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

E1-like activating enzyme Atg7 is preferentially sequestered into p62 aggregates via its interaction with LC3-I.

PubMed

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation's effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases.

Influence of antigen on immune complex behavior in mice.

PubMed

Finbloom, D S; Magilavy, D B; Harford, J B; Rifai, A; Plotz, P H

1981-07-01

To explore the possibility that the behavior of immune complexes can, under some circumstances, be directed by the antigen, we have studied the behavior of complexes of identical size made with the glycoproteins, orosomucoid (OR), and ceruloplasmin: or with their desialylated derivatives, asialo-orosomucoid (ASOR) and asialo-ceruloplasmin. Such desialylated proteins are rapidly removed from the circulation by a hepatic cell receptor for galactose, the sugar exposed upon removal of sialic acid. Mixtures of 125I-goat anti-ASOR with either ASOR or OR and mixtures of 125I-rabbit anti-OR with either ASOR or OR form complexes identically. The complexes were separated by density gradient centrifugation and injected intravenously into C3H mice. Blood clearance and hepatic uptake of the OR complexes and ASOR complexes were markedly different. T 1/2 for the goat OR complexes exceeded 300 min, whereas that for the ASOR complexes was 15 min. More detailed studies using rabbit complexes of various sizes revealed that light rabbit complexes behaved similarly to the goat complexes. The light rabbit OR complexes were cleared slowly, with only 18% found in the liver at 60 min, whereas the light rabbit ASOR complexes were cleared much more rapidly, with 62% found within the liver by 30 min. This rapid clearance was completely suppressed by a prior injection of a blocking dose of ASOR, which implies uptake by a galactose-mediated mechanism on hepatocytes. As the size of the rabbit complexes increased, so did the rate of Fc receptor-mediated clearance. Heavy rabbit OR complexes were cleared more rapidly than light OR complexes but not so rapidly as heavy ASOR complexes. The clearance and hepatic uptake of the heavy OR complexes were markedly suppressed by a prior injection of heat-aggregated gamma globulin, a known Fc receptor-blocking agent (45% hepatic uptake without and 6% with aggregated gamma globulin). The heavy rabbit ASOR complexes exhibited inhibition of blood clearance and hepatic uptake by both galactose receptor-blocking and Fc receptor-blocking agents. A blocking dose of ASOR reduced the hepatic uptake at 30 min from 75 to 49%, and heat-aggregated gamma globulin reduced it from 75 to 39%, which suggests that these heavy complexes were removed from the circulation by receptors both for the immunoglobulin and for the antigen. Cell separation studies and autoradiographs confirmed that those complexes cleared primarily by galactose-mediated mechanism were within hepatocytes, and those cleared by Fc receptors were within the nonparenchymal cells of the liver. It seems probable, therefore, the some antigen-antibody complexes may be removed from the circulation via receptors not only for immunoglobulin but also for antigen.

Influence of pea protein aggregates on the structure and stability of pea protein/soybean polysaccharide complex emulsions.

PubMed

Yin, Baoru; Zhang, Rujing; Yao, Ping

2015-03-20

The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS), and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry.

Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases

PubMed Central

Castillo, Virginia; Ventura, Salvador

2009-01-01

Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins. PMID:19696882

A reversible decrease in ribulose 1,5-bisphosphate carboxylase/oxygenase carboxylation activity caused by the aggregation of the enzyme's large subunit is triggered in response to the exposure of moderate irradiance-grown plants to low irradiance.

PubMed

Grabsztunowicz, Magda; Górski, Zbigniew; Luciński, Robert; Jackowski, Grzegorz

2015-08-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is highly regulated in response to fluctuations in the environment, including changes in irradiance. However, no complex data are available on Rubisco regulatory mechanisms triggered in plants which are submitted to moderate-low irradiance shift. Therefore, we investigated in a comprehensive way the changes at the level of amount of Rubisco protein, its structural organization and carboxylase activity of the holoenzyme as triggered by exposure of moderate irradiance-grown Arabidopsis thaliana plants to low irradiance conditions. An exposure of moderate irradiance-grown plants to low irradiance for a single photoperiod caused the exclusion of a certain pool of Rubisco under altered conditions owing to oxidative modifications resulting in the formation of protein aggregates involving Rubisco large subunit (LS). As a result, both initial and total Rubisco carboxylase activities were reduced, whereas Rubisco activation state remained largely unchanged. The results of the determination of reactive oxygen species indicated that a moderate/low irradiance transition had stimulated (1) O2 accumulation and we strongly suggest that Rubisco oxidative modifications leading to formation of aggregates encompassing Rubisco-LS were triggered by (1) O2 . When moderate irradiance regime was resumed, the majority of Rubisco-LS containing aggregates tended to be resolubilized, and this allowed Rubisco carboxylation activities to be largely recovered, without changes in the activation state of the enzyme. In the longer term, these results allow us to better understand a complexity of Rubisco regulatory mechanisms activated in response to abiotic stresses and during recovery from the stresses. © 2015 Scandinavian Plant Physiology Society.

Universal timescales in the rheology of spheroid cell aggregates

NASA Astrophysics Data System (ADS)

Yu, Miao; Mahtabfar, Aria; Beleen, Paul; Foty, Ramsey; Zahn, Jeffrey; Shreiber, David; Liu, Liping; Lin, Hao

2017-11-01

The rheological properties of tissue play important roles in key biological processes including embryogenesis, cancer metastasis, and wound healing. Spheroid cell aggregate is a particularly interesting model system for the study of these phenomena. In the long time, they behave like drops with a surface tension. In the short, viscoelasticity also needs to be considered. In this work, we discover two coupled and universal timescales for spheroid aggregates. A total of 12 aggregate types (total aggregate number n =290) derived from L and GBM (glioblastoma multiforme) cells are studied with microtensiometer to obtain their surface tension. They are also allowed to relax upon release of the compression forces. The two timescales are observed during the relaxation process; their values do not depend on compression time nor the degree of deformation, and are consistent among all 12 types. Following prior work (Yu et al., Phys. Rev. Lett., 115:128303; Liu et al., J. Mech. Phys. Solids, 98:309-329) we use a rigorous mathematical theory to interpret the results, which reveals intriguing properties of the aggregates on both tissue and cellular levels. The mechanics of multicellular organization reflects both complexity and regularity due to strong active regulation.

Investigation of aggregation in solvent extraction of lanthanides by acidic extractants (organophosphorus and naphthenic acid)

USGS Publications Warehouse

Zhou, N.; Wu, J.; Yu, Z.; Neuman, R.D.; Wang, D.; Xu, G.

1997-01-01

Three acidic extractants (I) di(2-ethylhexyl) phosphoric acid (HDEHP), (II) 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (HEHPEHE) and (III) naphthenic acid were employed in preparing the samples for the characterization of the coordination structure of lanthanide-extractant complexes and the physicochemical nature of aggregates formed in the organic diluent of the solvent extraction systems. Photo correlation spectroscopy (PCS) results on the aggregates formed by the partially saponified HDEHP in n-heptane showed that the hydrodynamic radius of the aggregates was comparable to the molecular dimensions of HDEHP. The addition of 2-octanol into the diluent, by which the mixed solvent was formed, increased the dimensions of the corresponding aggregates. Aggregates formed from the lanthanide ions and HDEHP in the organic phase of the extraction systems were found very unstable. In the case of naphthenic acid, PCS data showed the formation of w/o microemulsion from the saponified naphthenic acid in the mixed solvent. The extraction of lanthanides by the saponified naphthenic acid in the mixed solvent under the given experimental conditions was a process of destruction of the w/o microemulsion. A possible mechanism of the breakdown of the w/o microemulsion droplets is discussed.

Formation and shape-control of hierarchical cobalt nanostructures using quaternary ammonium salts in aqueous media

PubMed Central

Deshmukh, Ruchi; Mehra, Anurag

2017-01-01

Aggregation and self-assembly are influenced by molecular interactions. With precise control of molecular interactions, in this study, a wide range of nanostructures ranging from zero-dimensional nanospheres to hierarchical nanoplates and spindles have been successfully synthesized at ambient temperature in aqueous solution. The nanostructures reported here are formed by aggregation of spherical seed particles (monomers) in presence of quaternary ammonium salts. Hydroxide ions and a magnetic moment of the monomers are essential to induce shape anisotropy in the nanostructures. The cobalt nanoplates are studied in detail, and a growth mechanism based on collision, aggregation, and crystal consolidation is proposed based on a electron microscopy studies. The growth mechanism is generalized for rods, spindles, and nearly spherical nanostructures, obtained by varying the cation group in the quaternary ammonium hydroxides. Electron diffraction shows different predominant lattice planes on the edge and on the surface of a nanoplate. The study explains, hereto unaddressed, the temporal evolution of complex magnetic nanostructures. These ferromagnetic nanostructures represent an interesting combination of shape anisotropy and magnetic characteristics. PMID:28326240

X-ray studies on crystalline complexes involving amino acids and peptides. XXXII. Effect of chirality on ionisation state, stoichiometry and aggregation in the complexes of oxalic acid with DL- and L-lysine.

PubMed

Venkatraman, J; Prabu, M M; Vijayan, M

1997-08-01

Crystals of the oxalic acid complex of DL-lysine (triclinic P1; a = 5.540(1), b = 10.764(2), c = 12.056(2) A, alpha = 77.8(1), beta = 80.6(1), gamma = 75.6(1).; R = 4.7% for 2023 observed reflections) contain lysine and semioxalate ions in the 1:1 ratio, whereas the ratio of lysine and semioxalate/oxalate ions is 2:3 in the crystals of the L-lysine complex (monoclinic P2(1); alpha = 4.906(1), b = 20.145(4), c = 12.455(1) A, beta = 92.5(1).; R = 4.4% for 1494 observed reflections). The amino acid molecule in the L-lysine complex has an unusual ionisation state with positively charged alpha- and side-chain amino groups and a neutral carboxyl group. The unlike molecules aggregate into separate alternating layers in the DL-lysine complex in a manner similar to that observed in several of the amino acid complexes. The L-lysine complex exhibits a new aggregation pattern which cannot be easily explained in terms of planar features, thus emphasizing the fundamental dependence of aggregation on molecular characteristics. Despite the differences in stoichiometry, ionisation state and long-range aggregation patterns, the basic element of aggregation in the two complexes exhibits considerable similarity.

Formation, aggregation and reactivity of amorphous ferric oxyhydroxides on dissociation of Fe(III)-organic complexes in dilute aqueous suspensions

NASA Astrophysics Data System (ADS)

Bligh, Mark W.; Waite, T. David

2010-10-01

While chemical reactions that take place at the surface of amorphous ferric oxides (AFO) are known to be important in aquatic systems, incorporation of these reactions into kinetic models is hindered by a lack of ability to reliably quantify the reactivity of the surface and the changes in reactivity that occur over time. Long term decreases in the reactivity of iron oxides may be considered to result from changes in the molecular structure of the solid, however, over shorter time scales where substantial aggregation may occur, the mechanisms of reactivity loss are less clear. Precipitation of AFO may be described as a combination of homogeneous and heterogeneous reactions, however, despite its potentially significant role, the latter reaction is usually neglected in kinetic models of aquatic processes. Here, we investigate the role of AFO in scavenging dissolved inorganic ferric (Fe(III)) species (Fe') via the heterogeneous precipitation reaction during the net dissociation of organically complexed Fe(III) in seawater. Using sulfosalicylic acid (SSA) as a model ligand, AFO was shown to play a significant role in inducing the net dissociation of the Fe-SSA complexes with equations describing both the heterogeneous precipitation reaction and the aging of AFO being required to adequately describe the experimental data. An aggregation based mechanism provided a good description of AFO aging over the short time scale of the experiments. The behaviour of AFO described here has implications for the bioavailability of iron in natural systems as a result of reactions involving AFO which are recognised to occur over time scales of minutes, including adsorption of Fe' and AFO dissolution, precipitation and ageing.

Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

DOE PAGES

Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun; ...

2015-12-18

We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so evenmore » when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.« less

Kinetics of temperature response of PEO-b-PNIPAM-b-PAA triblock terpolymer aggregates and of their complexes with lysozyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papagiannopoulos, Aristeidis; Meristoudi, Anastasia; Hong, Kunlun

We present the kinetics of temperature response of a PEO-b-PNIPAM-b-PAA triblock terpolymer and of its complexes with lysozyme in aqueous solution. It is found that during the coil-to-globule transition of PNIPAM new bonds within the polymer aggregates are created, making the transition of the aggregates partially irreversible. This effect is also found for the protein loaded PEO-b-PNIPAM-b-PAA aggregates whereas in this case protein globules appear to enhance the formation of bonds, making the transition totally irreversible. The internal dynamics of both aggregates and complexes are “frozen” once the temperature is increased upon PINIPAM's LCST in water and remain so evenmore » when the temperature drops below LCST. As a result, we investigate the complexation kinetics of lysozyme and PEO-b-PNIPAM-b-PAA and observe that it occurs in two stages, one where protein globules adsorb on single pre-formed aggregates and one where protein globules cause inter-aggregate clustering.« less

Structural and electronic properties of extremely long perylene bisimide nanofibers formed through a stoichiometrically mismatched, hydrogen-bonded complexation.

PubMed

Yagai, Shiki; Seki, Tomohiro; Murayama, Haruno; Wakikawa, Yusuke; Ikoma, Tadaaki; Kikkawa, Yoshihiro; Karatsu, Takashi; Kitamura, Akihide; Honsho, Yoshihito; Seki, Shu

2010-12-06

Extremely long nanofibers, whose lengths reach the millimeter regime, are generated via co-aggregation of a melamine-appended perylene bisimide semiconductor and a substituted cyanurate, both of which are ditopic triple-hydrogen-bonding building blocks; they co-aggregate in an unexpected stoichiometrically mismatched 1:2 ratio. Various microscopic and X-ray diffraction studies suggest that hydrogen-bonded polymeric chains are formed along the long axis of the nanofibers by the 1:2 complexation of the two components, which further stack along the short axis of the nanofibers. The photocarrier generation mechanism in the nanofibers is investigated by time-of-flight (TOF) experiments under electric and magnetic fields, revealing the birth and efficient recombination of singlet geminate electron-hole pairs. Flash-photolysis time-resolved microwave conductivity (FP-TRMC) measurements revealed intrinsic 1D electron mobilities up to 0.6 cm(2) V(-1) s(-1) within nanofibers.

The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions

NASA Astrophysics Data System (ADS)

Liao, Jiahn-Haur; Wu, Tzu-Hua; Chen, Ming-Yi; Chen, Wei-Ting; Lu, Shou-Yun; Wang, Yi-Hsuan; Wang, Shao-Pin; Hsu, Yen-Min; Huang, Yi-Shiang; Huang, Zih-You; Lin, Yu-Ching; Chang, Ching-Ming; Huang, Fu-Yung; Wu, Shih-Hsiung

2015-12-01

In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO32- and DCCM/SeO32- complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

Excavation and aggregation as organizing factors in de novo construction by mound-building termites.

PubMed

Green, Ben; Bardunias, Paul; Turner, J Scott; Nagpal, Radhika; Werfel, Justin

2017-06-14

Termites construct complex mounds that are orders of magnitude larger than any individual and fulfil a variety of functional roles. Yet the processes through which these mounds are built, and by which the insects organize their efforts, remain poorly understood. The traditional understanding focuses on stigmergy, a form of indirect communication in which actions that change the environment provide cues that influence future work. Termite construction has long been thought to be organized via a putative 'cement pheromone': a chemical added to deposited soil that stimulates further deposition in the same area, thus creating a positive feedback loop whereby coherent structures are built up. To investigate the detailed mechanisms and behaviours through which termites self-organize the early stages of mound construction, we tracked the motion and behaviour of major workers from two Macrotermes species in experimental arenas. Rather than a construction process focused on accumulation of depositions, as models based on cement pheromone would suggest, our results indicated that the primary organizing mechanisms were based on excavation. Digging activity was focused on a small number of excavation sites, which in turn provided templates for soil deposition. This behaviour was mediated by a mechanism of aggregation, with termites being more likely to join in the work at an excavation site as the number of termites presently working at that site increased. Statistical analyses showed that this aggregation mechanism was a response to active digging, distinct from and unrelated to putative chemical cues that stimulate deposition. Agent-based simulations quantitatively supported the interpretation that the early stage of de novo construction is primarily organized by excavation and aggregation activity rather than by stigmergic deposition. © 2017 The Author(s).

Excavation and aggregation as organizing factors in de novo construction by mound-building termites

PubMed Central

Bardunias, Paul; Turner, J. Scott; Nagpal, Radhika; Werfel, Justin

2017-01-01

Termites construct complex mounds that are orders of magnitude larger than any individual and fulfil a variety of functional roles. Yet the processes through which these mounds are built, and by which the insects organize their efforts, remain poorly understood. The traditional understanding focuses on stigmergy, a form of indirect communication in which actions that change the environment provide cues that influence future work. Termite construction has long been thought to be organized via a putative ‘cement pheromone’: a chemical added to deposited soil that stimulates further deposition in the same area, thus creating a positive feedback loop whereby coherent structures are built up. To investigate the detailed mechanisms and behaviours through which termites self-organize the early stages of mound construction, we tracked the motion and behaviour of major workers from two Macrotermes species in experimental arenas. Rather than a construction process focused on accumulation of depositions, as models based on cement pheromone would suggest, our results indicated that the primary organizing mechanisms were based on excavation. Digging activity was focused on a small number of excavation sites, which in turn provided templates for soil deposition. This behaviour was mediated by a mechanism of aggregation, with termites being more likely to join in the work at an excavation site as the number of termites presently working at that site increased. Statistical analyses showed that this aggregation mechanism was a response to active digging, distinct from and unrelated to putative chemical cues that stimulate deposition. Agent-based simulations quantitatively supported the interpretation that the early stage of de novo construction is primarily organized by excavation and aggregation activity rather than by stigmergic deposition. PMID:28615497

Morphology and formation mechanism in precipitation of calcite induced by Curvibacter lanceolatus strain HJ-1

NASA Astrophysics Data System (ADS)

Zhang, Chonghong; Li, Fuchun; Lv, Jiejie

2017-11-01

Precipitation of calcium carbobate induced by microbial activities is common occurrence in controlled solution, but the formation mechanism and morphology in precipitation of calcite in solution systems is unclear, and the role of microbes is disputed. Here, culture experiment was performed for 50 days using the Curvibacter lanceolatus strain HJ-1 in a M2 culture medium, and the phase composition and morphology of the precipitates were characterized by the X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) techniques. We show that the precipitation processes in our experiment lead to unusual morphologies of crystals corresponding to different growth stages, and the morphologies of the precipitated crystal aggregates ranging from the main rod-, cross-, star-, cauliflower-like morphologies to spherulitic structure. The complex and unusual morphologies of the precipitated calcite by strain HJ-1 may provide a reference point for better understanding the biomineralization mechanism of calcite, moreover, morphological transition of minerals revealed that the multi-ply crystals-aggregation mechanism for calcite growth in crystallisation media.

A coarse grained protein model with internal degrees of freedom. Application to α-synuclein aggregation

NASA Astrophysics Data System (ADS)

Ilie, Ioana M.; den Otter, Wouter K.; Briels, Wim J.

2016-02-01

Particles in simulations are traditionally endowed with fixed interactions. While this is appropriate for particles representing atoms or molecules, objects with significant internal dynamics—like sequences of amino acids or even an entire protein—are poorly modelled by invariable particles. We develop a highly coarse grained polymorph patchy particle with the ultimate aim of simulating proteins as chains of particles at the secondary structure level. Conformational changes, e.g., a transition between disordered and β-sheet states, are accommodated by internal coordinates that determine the shape and interaction characteristics of the particles. The internal coordinates, as well as the particle positions and orientations, are propagated by Brownian Dynamics in response to their local environment. As an example of the potential offered by polymorph particles, we model the amyloidogenic intrinsically disordered protein α-synuclein, involved in Parkinson's disease, as a single particle with two internal states. The simulations yield oligomers of particles in the disordered state and fibrils of particles in the "misfolded" cross-β-sheet state. The aggregation dynamics is complex, as aggregates can form by a direct nucleation-and-growth mechanism and by two-step-nucleation through conversions between the two cluster types. The aggregation dynamics is complex, with fibrils formed by direct nucleation-and-growth, by two-step-nucleation through the conversion of an oligomer and by auto-catalysis of this conversion.

Volcanic ash aggregation in the lab - can we mimic natural processes?

NASA Astrophysics Data System (ADS)

Mueller, Sebastian B.; Kueppers, Ulrich; Jacob, Michael; Ayris, Paul; Cimarelli, Corrado; Dingwell, Donald B.; Guttzeit, Melanie; Hess, Kai-Uwe; Walter, Ulrich

2015-04-01

Explosive volcanic eruptions release large amounts of particles into the atmosphere. Volcanic ash, by definition pyroclasts smaller than 2 mm, can be distributed around the globe by prevailing winds. Ash poses hazards to aviation industry by melting in jet turbines, to human health by entering respiration systems and to society by damaging infrastructure. Under certain circumstances, ash particles can cluster together and build ash aggregates. Aggregates range in size from few mm to few cm and may exhibit complex internal stratigraphy. During growth, weight, density and aerodynamic properties change, leading to a significantly different settling behavior compared to individual ash particles. Although ash aggregation has been frequently observed in the geologic record, the physical and chemical mechanisms generating the aggregates remain poorly understood. During several field campaigns, we collected numerous ash aggregates and analyzed their textural, chemical and mechanical properties. Based on this knowledge, we have designed experiments using the ProCell Lab System® of Glatt Ingenieurtechnik GmbH, Germany. In this device, a continuous fluidized bed can be applied on solid particles and simulate gas-particle flow conditions as they would be expected in volcanic plumes or pyroclastic density currents. The geological record and direct observations have shown that both processes are capable of producing ash aggregates. As starting material we used Na-glass beads as an analogue and volcanic ash from Laacher See Volcano, Eifel Volcanic Field, Germany. We define parameters such as grainsize, specific surface area and concentration of the starting material, degree of turbulence, temperature and moisture in the process chamber and the composition of the liquid phase to influence form, size, stability and production rate of aggregates. We were able to experimentally produce round, unstructured ash pellets up to 5mm in diameter. A detailed textural description highlights the strongly different properties of single ash grains and ash aggregates. These experiments aim at experimentally constraining the boundary conditions required for the generation of strong ash aggregates. A better mechanistic understanding will serve for more adequate ash mass distribution modeling.

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

PubMed

Genser, Bernd; Fischer, Joachim E; Figueiredo, Camila A; Alcântara-Neves, Neuza; Barreto, Mauricio L; Cooper, Philip J; Amorim, Leila D; Saemann, Marcus D; Weichhart, Thomas; Rodrigues, Laura C

2016-05-20

Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

Dielectric and electric properties as a tool to investigate the coagulation mechanism during sludge treatment.

PubMed

Mortadi, A; Chahid, El G; Nasrellah, H; Cherkaoui, O; El Moznine, R

2017-09-28

The analysis of the complex permittivity, electrical complex modulus and the hopping conductivity have been employed in order to investigate the impacts of calcium oxide during sludge treatment in textile such as coagulation process. In this context, impedance measurement was performed on five samples, including raw sludge and four compositions containing different amounts of calcium oxide: 2%, 3%, 4% and 5% (w/w). The dielectric spectra of each composition were described by the summation of a power law and a Cole-Cole relaxation model. The relaxation time and the magnitude of the dielectric relaxation obtained from the analysis of dielectric properties showed an increase up to 3% of these parameters with the addition of calcium oxide. Above this critical value, both parameters showed a very small change, suggesting that the aggregation became more stable. In addition, the evolution of the hopping conductivity reached a minimum value at this critical amount (3%). This evolution was well described by a double power law, which allowed us to estimate the optimal amount of the calcium oxide to achieve coagulation process. The analysis of the dielectric properties was found useful in monitoring aggregation processes that occur during the coagulation mechanism in textile sludge.

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

PubMed Central

Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

The ongoing search for small molecules to study metal-associated amyloid-β species in Alzheimer's disease.

PubMed

Savelieff, Masha G; DeToma, Alaina S; Derrick, Jeffrey S; Lim, Mi Hee

2014-08-19

The development of a cure for Alzheimer's disease (AD) has been impeded by an inability to pinpoint the root cause of this disorder. Although numerous potential pathological factors have been indicated, acting either individually or mutually, the molecular mechanisms leading to disease onset and progression have not been clear. Amyloid-β (Aβ), generated from proteolytic processing of the amyloid precursor protein (APP), and its aggregated forms, particularly oligomers, are suggested as key pathological features in AD-affected brains. Historically, highly concentrated metals are found colocalized within Aβ plaques. Metal binding to Aβ (metal-Aβ) generates/stabilizes potentially toxic Aβ oligomers, and produces reactive oxygen species (ROS) in vitro (redox active metal ions; plausible contribution to oxidative stress). Consequently, clarification of the relationship between Aβ, metal ions, and toxicity, including oxidative stress via metal-Aβ, can lead to a deeper understanding of AD development. To probe the involvement of metal-Aβ in AD pathogenesis, rationally designed and naturally occurring molecules have been examined as chemical tools to target metal-Aβ species, modulate the interaction between the metal and Aβ, and subsequently redirect their aggregation into nontoxic, off-pathway unstructured aggregates. These ligands are also capable of attenuating the generation of redox active metal-Aβ-induced ROS to mitigate oxidative stress. One rational design concept, the incorporation approach, installs a metal binding site into a framework known to interact with Aβ. This approach affords compounds with the simultaneous ability to chelate metal ions and interact with Aβ. Natural products capable of Aβ interaction have been investigated for their influence on metal-induced Aβ aggregation and have inspired the construction of synthetic analogues. Systematic studies of these synthetic or natural molecules could uncover relationships between chemical structures, metal/Aβ/metal-Aβ interactions, and inhibition of Aβ/metal-Aβ reactivity (i.e., aggregation modes of Aβ/metal-Aβ; associated ROS production), suggesting mechanisms to refine the design strategy. Interdisciplinary investigations have demonstrated that the designed molecules and natural products control the aggregation pathways of metal-Aβ species transforming their size/conformation distribution. The aptitude of these molecules to impact metal-Aβ aggregation pathways, either via inhibition of Aβ aggregate formation, most importantly of oligomers, or disaggregation of preformed fibrils, could originate from their formation of complexes with metal-Aβ. Potentially, these molecules could direct metal-Aβ size/conformational states into alternative nontoxic unstructured oligomers, and control the geometry at the Aβ-ligated metal center for limited ROS formation to lessen the overall toxicity induced by metal-Aβ. Complexation between small molecules and Aβ/metal-Aβ has been observed by nuclear magnetic resonance spectroscopy (NMR) and ion mobility-mass spectrometry (IM-MS) pointing to molecular level interactions, validating the design strategy. In addition, these molecules exhibit other attractive properties, such as antioxidant capacity, prevention of ROS production, potential blood-brain barrier (BBB) permeability, and reduction of Aβ-/metal-Aβ-induced cytotoxicity, making them desirable tools for unraveling AD complexity. In this Account, we summarize the recent development of small molecules, via both rational design and the selection and modification of natural products, as tools for investigating metal-Aβ complexes, to advance our understanding of their relation to AD pathology.

Joint histogram-based cost aggregation for stereo matching.

PubMed

Min, Dongbo; Lu, Jiangbo; Do, Minh N

2013-10-01

This paper presents a novel method for performing efficient cost aggregation in stereo matching. The cost aggregation problem is reformulated from the perspective of a histogram, giving us the potential to reduce the complexity of the cost aggregation in stereo matching significantly. Differently from previous methods which have tried to reduce the complexity in terms of the size of an image and a matching window, our approach focuses on reducing the computational redundancy that exists among the search range, caused by a repeated filtering for all the hypotheses. Moreover, we also reduce the complexity of the window-based filtering through an efficient sampling scheme inside the matching window. The tradeoff between accuracy and complexity is extensively investigated by varying the parameters used in the proposed method. Experimental results show that the proposed method provides high-quality disparity maps with low complexity and outperforms existing local methods. This paper also provides new insights into complexity-constrained stereo-matching algorithm design.

Genetic variation in aggregation behaviour and interacting phenotypes in Drosophila.

PubMed

Philippe, Anne-Sophie; Jeanson, Raphael; Pasquaretta, Cristian; Rebaudo, Francois; Sueur, Cedric; Mery, Frederic

2016-03-30

Aggregation behaviour is the tendency for animals to group together, which may have important consequences on individual fitness. We used a combination of experimental and simulation approaches to study how genetic variation and social environment interact to influence aggregation dynamics in Drosophila To do this, we used two different natural lines of Drosophila that arise from a polymorphism in the foraging gene (rovers and sitters). We placed groups of flies in a heated arena. Flies could freely move towards one of two small, cooler refuge areas. In groups of the same strain, sitters had a greater tendency to aggregate. The observed behavioural variation was based on only two parameters: the probability of entering a refuge and the likelihood of choosing a refuge based on the number of individuals present. We then directly addressed how different strains interact by mixing rovers and sitters within a group. Aggregation behaviour of each line was strongly affected by the presence of the other strain, without changing the decision rules used by each. Individuals obeying local rules shaped complex group dynamics via a constant feedback loop between the individual and the group. This study could help to identify the circumstances under which particular group compositions may improve individual fitness through underlying aggregation mechanisms under specific environmental conditions. © 2016 The Author(s).

Heavy metal removal capacity of individual components of permeable reactive concrete

NASA Astrophysics Data System (ADS)

Holmes, Ryan R.; Hart, Megan L.; Kevern, John T.

2017-01-01

Permeable reactive barriers (PRBs) are a well-known technique for groundwater remediation using industrialized reactive media such as zero-valent iron and activated carbon. Permeable reactive concrete (PRC) is an alternative reactive medium composed of relatively inexpensive materials such as cement and aggregate. A variety of multimodal, simultaneous processes drive remediation of metals from contaminated groundwater within PRC systems due to the complex heterogeneous matrix formed during cement hydration. This research investigated the influence coarse aggregate, portland cement, fly ash, and various combinations had on the removal of lead, cadmium, and zinc in solution. Absorption, adsorption, precipitation, co-precipitation, and internal diffusion of the metals are common mechanisms of removal in the hydrated cement matrix and independent of the aggregate. Local aggregates can be used as the permeable structure also possessing high metal removal capabilities, however calcareous sources of aggregate are preferred due to improved removal with low leachability. Individual adsorption isotherms were linear or curvilinear up, indicating a preferred removal process. For PRC samples, metal saturation was not reached over the range of concentrations tested. Results were then used to compare removal against activated carbon and aggregate-based PRBs by estimating material costs for the remediation of an example heavy metal contaminated Superfund site located in the Midwestern United States, Joplin, Missouri.

Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma

PubMed Central

Kintzer, Alexander F.; Sterling, Harry J.; Tang, Iok I.; Abdul-Gader, Ali; Miles, Andrew J.; Wallace, B. A.; Williams, Evan R.; Krantz, Bryan A.

2010-01-01

Anthrax is caused by strains of Bacillus anthracis that produce two key virulence factors, anthrax toxin (Atx) and a poly-γ-D-glutamic acid capsule. Atx is comprised of three-proteins: protective antigen (PA) and two enzymes, lethal factor (LF) and edema factor (EF). To disrupt cell function, these components must assemble into holotoxin complexes, which contain either a ring-shaped homooctameric or homoheptameric PA oligomer bound to multiple copies of either LF and/or EF, producing lethal toxin (LT), edema toxin, or mixtures thereof. Once a host cell endocytoses these complexes, PA converts into a membrane-inserted channel that translocates LF and EF into the cytosol. LT may assemble on host cell surfaces or extracellularly in plasma. We show that under physiological conditions in bovine plasma that LT complexes containing heptameric PA aggregate and inactivate more readily than LT complexes containing octameric PA. LT complexes containing octameric PA possess enhanced stability, channel forming activity, and macrophage cytotoxicity relative to those containing heptameric PA. Under physiological conditions, multiple biophysical probes reveal that heptameric PA can prematurely adopt the channel conformation, but octameric PA complexes remain in their soluble prechannel configuration allowing them to resist aggregation and inactivation. We conclude that PA may form an octameric oligomeric state as a means to produce a more stable and active LT complex that may circulate freely in the blood. PMID:20433851

Comparing the energy landscapes for native folding and aggregation of PrP

PubMed Central

Dee, Derek R.; Woodside, Michael T.

2016-01-01

ABSTRACT Protein sequences are evolved to encode generally one folded structure, out of a nearly infinite array of possible folds. Underlying this code is a funneled free energy landscape that guides folding to the native conformation. Protein misfolding and aggregation are also a manifestation of free-energy landscapes. The detailed mechanisms of these processes are poorly understood, but often involve rare, transient species and a variety of different pathways. The inherent complexity of misfolding has hampered efforts to measure aggregation pathways and the underlying energy landscape, especially using traditional methods where ensemble averaging obscures important rare and transient events. We recently studied the misfolding and aggregation of prion protein by examining 2 monomers tethered in close proximity as a dimer, showing how the steps leading to the formation of a stable aggregated state can be resolved in the single-molecule limit and the underlying energy landscape thereby reconstructed. This approach allows a more quantitative comparison of native folding versus misfolding, including fundamental differences in the dynamics for misfolding. By identifying key steps and interactions leading to misfolding, it should help to identify potential drug targets. Here we describe the importance of characterizing free-energy landscapes for aggregation and the challenges involved in doing so, and we discuss how single-molecule studies can help test proposed structural models for PrP aggregates. PMID:27191683

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity.

PubMed

Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

2012-09-25

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity.

The Myxococcus xanthus Spore Cuticula Protein C Is a Fragment of FibA, an Extracellular Metalloprotease Produced Exclusively in Aggregated Cells

PubMed Central

Lee, Bongsoo; Mann, Petra; Grover, Vidhi; Treuner-Lange, Anke; Kahnt, Jörg; Higgs, Penelope I.

2011-01-01

Myxococcus xanthus is a soil bacterium with a complex life cycle involving distinct cell fates, including production of environmentally resistant spores to withstand periods of nutrient limitation. Spores are surrounded by an apparently self-assembling cuticula containing at least Proteins S and C; the gene encoding Protein C is unknown. During analyses of cell heterogeneity in M. xanthus, we observed that Protein C accumulated exclusively in cells found in aggregates. Using mass spectrometry analysis of Protein C either isolated from spore cuticula or immunoprecipitated from aggregated cells, we demonstrate that Protein C is actually a proteolytic fragment of the previously identified but functionally elusive zinc metalloprotease, FibA. Subpopulation specific FibA accumulation is not due to transcriptional regulation suggesting post-transcriptional regulation mechanisms mediate its heterogeneous accumulation patterns. PMID:22174937

Economic dynamics with financial fragility and mean-field interaction: A model

NASA Astrophysics Data System (ADS)

Di Guilmi, C.; Gallegati, M.; Landini, S.

2008-06-01

Following Aoki’s statistical mechanics methodology [Masanao Aoki, New Approaches to Macroeconomic Modeling, Cambridge University Press, 1996; Masanao Aoki, Modeling Aggregate Behaviour and Fluctuations in Economics, Cambridge University Press, 2002; Masanao Aoki, and Hiroshi Yoshikawa, Reconstructing Macroeconomics, Cambridge University Press, 2006], we provide some insights into the well-known works of [Bruce Greenwald, Joseph Stiglitz, Macroeconomic models with equity and credit rationing, in: R. Hubbard (Ed.), Information, Capital Markets and Investment, Chicago University Press, Chicago, 1990; Bruce Greenwald, Joseph Stiglitz, Financial markets imperfections and business cycles, Quarterly journal of Economics (1993)]. Specifically, we reach analytically a closed form solution of their models overcoming the aggregation problem. The key idea is to represent the economy as an evolving complex system, composed by heterogeneous interacting agents, that can be partitioned into a space of macroscopic states. This meso level of aggregation permits to adopt mean-field interaction modeling and master equation techniques.

The amyloid interactome: Exploring protein aggregation

PubMed Central

Mastrokalou, Chara V.; Hamodrakas, Stavros J.

2017-01-01

Protein-protein interactions are the quintessence of physiological activities, but also participate in pathological conditions. Amyloid formation, an abnormal protein-protein interaction process, is a widespread phenomenon in divergent proteins and peptides, resulting in a variety of aggregation disorders. The complexity of the mechanisms underlying amyloid formation/amyloidogenicity is a matter of great scientific interest, since their revelation will provide important insight on principles governing protein misfolding, self-assembly and aggregation. The implication of more than one protein in the progression of different aggregation disorders, together with the cited synergistic occurrence between amyloidogenic proteins, highlights the necessity for a more universal approach, during the study of these proteins. In an attempt to address this pivotal need we constructed and analyzed the human amyloid interactome, a protein-protein interaction network of amyloidogenic proteins and their experimentally verified interactors. This network assembled known interconnections between well-characterized amyloidogenic proteins and proteins related to amyloid fibril formation. The consecutive extended computational analysis revealed significant topological characteristics and unraveled the functional roles of all constituent elements. This study introduces a detailed protein map of amyloidogenicity that will aid immensely towards separate intervention strategies, specifically targeting sub-networks of significant nodes, in an attempt to design possible novel therapeutics for aggregation disorders. PMID:28249044

Mechanical Performance Evaluation of Self-Compacting Concrete with Fine and Coarse Recycled Aggregates from the Precast Industry.

PubMed

Santos, Sara A; da Silva, Pedro R; de Brito, Jorge

2017-08-04

This paper intends to evaluate the feasibility of reintroducing recycled concrete aggregates in the precast industry. The mechanical properties of self-compacting concrete (SCC) with incorporation of recycled aggregates (RA) (coarse recycled aggregates (CRA) and fine recycled aggregates (FRA)) from crushed precast elements were evaluated. The goal was to evaluate the ability of producing SCC with a minimum pre-established performance in terms of mechanical strength, incorporating variable ratios of RA (FRA/CRA%: 0/0%, 25/25%, 50/50%, 0/100% and 100/0%) produced from precast source concretes with similar target performances. This replication in SCC was made for two strength classes (45 MPa and 65 MPa), with the intention of obtaining as final result concrete with recycled aggregates whose characteristics are compatible with those of a SCC with natural aggregates in terms of workability and mechanical strength. The results enabled conclusions to be established regarding the SCC's produced with fine and coarse recycled aggregates from the precast industry, based on its mechanical properties. The properties studied are strongly affected by the type and content of recycled aggregates. The potential demonstrated, mainly in the hardened state, by the joint use of fine and coarse recycled aggregate is emphasized.

Mechanical Performance Evaluation of Self-Compacting Concrete with Fine and Coarse Recycled Aggregates from the Precast Industry

PubMed Central

Santos, Sara A.; da Silva, Pedro R.; de Brito, Jorge

2017-01-01

This paper intends to evaluate the feasibility of reintroducing recycled concrete aggregates in the precast industry. The mechanical properties of self-compacting concrete (SCC) with incorporation of recycled aggregates (RA) (coarse recycled aggregates (CRA) and fine recycled aggregates (FRA)) from crushed precast elements were evaluated. The goal was to evaluate the ability of producing SCC with a minimum pre-established performance in terms of mechanical strength, incorporating variable ratios of RA (FRA/CRA%: 0/0%, 25/25%, 50/50%, 0/100% and 100/0%) produced from precast source concretes with similar target performances. This replication in SCC was made for two strength classes (45 MPa and 65 MPa), with the intention of obtaining as final result concrete with recycled aggregates whose characteristics are compatible with those of a SCC with natural aggregates in terms of workability and mechanical strength. The results enabled conclusions to be established regarding the SCC’s produced with fine and coarse recycled aggregates from the precast industry, based on its mechanical properties. The properties studied are strongly affected by the type and content of recycled aggregates. The potential demonstrated, mainly in the hardened state, by the joint use of fine and coarse recycled aggregate is emphasized. PMID:28777316

Natural Products with Antiplatelet Action.

PubMed

Hirsch, Gabriela Elisa; Viecili, Paulo Ricardo Nazario; de Almeida, Amanda Spring; Nascimento, Sabrina; Porto, Fernando Garcez; Otero, Juliana; Schmidt, Aline; da Silva, Brenda; Parisi, Mariana Migliorini; Klafke, Jonatas Zeni

2017-01-01

Complex hemostatic mechanisms are involved in the pathophysiology of various diseases, including cardiovascular diseases. Among them, dysregulation of platelet activity is linked to the progression of atherosclerosis and mainly involves platelet aggregation and a decrease in blood flow in the vascular endothelium. The major platelet activation pathways mediated by agonists involve the arachidonic acid pathway, adenosine diphosphate pathway, serotonin pathway, nitric oxide pathway, and action of free radicals on molecules involved in platelet aggregation. These mechanisms have been widely studied and discussed because they are inhibited by the use of medicinal plants in complementary and alternative medicine, thus reducing platelet aggregation. Of the main plants discussed in this review, which have antiplatelet activity, some include saffron, garlic, green tea, St. John's wort, ginger, ginkgo biloba, ginseng, and guavirova. These herbal medicines have phytochemical components, which are directly related to the antiplatelet activity of the plant, such as flavonoids, curcumins, catechins, terpenoids, polyphenols, and saponins. While the majority of the medicinal plants mentioned here were native to the Asian continents, some are distributed worldwide, and found to a smaller extent throughout the American continent, European continent, Mediterranean, African continent, and the Middle East. This review showed that several plants and/or compounds exhibit anti-platelet activity, and are therefore potential research targets for developing drugs to treat diseases related to aggregation disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity**

PubMed Central

Malina, Jaroslav; Farrell, Nicholas P.; Brabec, Viktor

2015-01-01

The trinuclear platinum complexes ([{Pt(NH3)3}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]6+, TriplatinNC‐A; [{trans-Pt(NH3)2(NH2(CH2)6NH3+)}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]8+, TriplatinNC) belong to a class of biologically active agents that bind to DNA via nonbonding noncovalent (hydrogen bonding, electrostatic) interactions. Charge delocalization (6+ to 8+) in these linear trinuclear platinum complexes results in a high cellular uptake and promising cytotoxic activity in several carcinoma cell lines. We show in the present work with the aid of the methods of biophysical chemistry that in particular TriplatinNC condenses DNA with unprecedented potency which is much higher than that of conventional DNA condensing agents. In addition, in contrast to other DNA condensing agents, both platinum complexes induce aggregation of small transfer RNA molecules. We also demonstrate for the first time that TriplatinNC-A and TriplatinNC in particular completely inhibit DNA transcriptional activity at markedly lower concentration than naturally occurring spermine. Notably, the topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at ~60-fold and ~250-fold lower concentration than that of spermine, respectively. We suggest that the general mechanisms of biological activity of TriplatinNC-A and TriplatinNC may be associated with their unique ability to condense/aggregate nucleic acids with consequent inhibitory effect on crucial enzymatic activities. PMID:25256921

Microbial activities and dissolved organic matter dynamics in oil-contaminated surface seawater from the Deepwater Horizon oil spill site.

PubMed

Ziervogel, Kai; McKay, Luke; Rhodes, Benjamin; Osburn, Christopher L; Dickson-Brown, Jennifer; Arnosti, Carol; Teske, Andreas

2012-01-01

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities.

Microbial Activities and Dissolved Organic Matter Dynamics in Oil-Contaminated Surface Seawater from the Deepwater Horizon Oil Spill Site

PubMed Central

Ziervogel, Kai; McKay, Luke; Rhodes, Benjamin; Osburn, Christopher L.; Dickson-Brown, Jennifer; Arnosti, Carol; Teske, Andreas

2012-01-01

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities. PMID:22509359

Molecular mechanism of tau aggregation induced by anionic and cationic dyes.

PubMed

Lira-De León, Karla I; García-Gutiérrez, Ponciano; Serratos, Iris N; Palomera-Cárdenas, Marianela; Figueroa-Corona, María Del P; Campos-Peña, Victoria; Meraz-Ríos, Marco A

2013-01-01

Abnormal tau filaments are a hallmark of Alzheimer's disease. Anionic dyes such as Congo Red, Thiazine Red, and Thioflavin S are able to induce tau fibrillization in vitro. SH-SY5Y cells were incubated with each dye for seven days leading to intracellular aggregates of tau protein, with different morphological characteristics. Interestingly, these tau aggregates were not observed when the Methylene Blue dye was added to the cell culture. In order to investigate the molecular mechanisms underlying this phenomenon, we developed a computational model for the interaction of the tau paired helical filament (PHF) core with every dye by docking analysis. The polar/electrostatic and nonpolar contribution to the free binding energy in the tau PHF core-anionic dye interaction was determined. We found that the tau PHF core can generate a positive net charge within the binding site localized at residuesLys311 and Lys340 (numbering according to the longest isoform hTau40). These residues are important for the binding affinity of the negative charges present in the anionic dyes causing an electrostatic environment that stabilizes the complex. Tau PHF core protofibril-Congo Red interaction has a stronger binding affinity compared to Thiazine Red or Thioflavin S. By contrast, the cationic dye Methylene Blue does not bind to nor stabilize the tau PHF core protofibrils. These results characterize the driving forces responsible for the binding of tau to anionic dyes leading to their self-aggregation and suggest that Methylene Blue may act as a destabilizing agent of tau aggregates.

Structure and properties of a complex of α-synuclein and a single-domain camelid antibody.

PubMed

De Genst, Erwin J; Guilliams, Tim; Wellens, Joke; O'Day, Elizabeth M; Waudby, Christopher A; Meehan, Sarah; Dumoulin, Mireille; Hsu, Shang-Te Danny; Cremades, Nunilo; Verschueren, Koen H G; Pardon, Els; Wyns, Lode; Steyaert, Jan; Christodoulou, John; Dobson, Christopher M

2010-09-17

The aggregation of the intrinsically disordered protein α-synuclein to form fibrillar amyloid structures is intimately associated with a variety of neurological disorders, most notably Parkinson's disease. The molecular mechanism of α-synuclein aggregation and toxicity is not yet understood in any detail, not least because of the paucity of structural probes through which to study the behavior of such a disordered system. Here, we describe an investigation involving a single-domain camelid antibody, NbSyn2, selected by phage display techniques to bind to α-synuclein, including the exploration of its effects on the in vitro aggregation of the protein under a variety of conditions. We show using isothermal calorimetric methods that NbSyn2 binds specifically to monomeric α-synuclein with nanomolar affinity and by means of NMR spectroscopy that it interacts with the four C-terminal residues of the protein. This latter finding is confirmed by the determination of a crystal structure of NbSyn2 bound to a peptide encompassing the nine C-terminal residues of α-synuclein. The NbSyn2:α-synuclein interaction is mediated mainly by side-chain interactions while water molecules cross-link the main-chain atoms of α-synuclein to atoms of NbSyn2, a feature we believe could be important in intrinsically disordered protein interactions more generally. The aggregation behavior of α-synuclein at physiological pH, including the morphology of the resulting fibrillar structures, is remarkably unaffected by the presence of NbSyn2 and indeed we show that NbSyn2 binds strongly to the aggregated as well as to the soluble forms of α-synuclein. These results give strong support to the conjecture that the C-terminal region of the protein is not directly involved in the mechanism of aggregation and suggest that binding of NbSyn2 could be a useful probe for the identification of α-synuclein aggregation in vitro and possibly in vivo. Copyright © 2010. Published by Elsevier Ltd.

Conformational Equilibria in Monomeric α-Synuclein at the Single-Molecule Level

PubMed Central

Tessari, Isabella; Mammi, Stefano; Bergantino, Elisabetta; Musiani, Francesco; Brucale, Marco; Bubacco, Luigi; Samorì, Bruno

2008-01-01

Human α-Synuclein (αSyn) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to researchers attempting to decipher the molecular mechanisms of αSyn aggregation and formation of fibrils. Traditional bulk techniques used so far to solve this problem point to a direct correlation between αSyn's unique conformational properties and its propensity to aggregate, but these techniques can only provide ensemble-averaged information for monomers and oligomers alike. They therefore cannot characterize the full complexity of the conformational equilibria that trigger the aggregation process. We applied atomic force microscopy–based single-molecule mechanical unfolding methodology to study the conformational equilibrium of human wild-type and mutant αSyn. The conformational heterogeneity of monomeric αSyn was characterized at the single-molecule level. Three main classes of conformations, including disordered and “β-like” structures, were directly observed and quantified without any interference from oligomeric soluble forms. The relative abundance of the “β-like” structures significantly increased in different conditions promoting the aggregation of αSyn: the presence of Cu2+, the pathogenic A30P mutation, and high ionic strength. This methodology can explore the full conformational space of a protein at the single-molecule level, detecting even poorly populated conformers and measuring their distribution in a variety of biologically important conditions. To the best of our knowledge, we present for the first time evidence of a conformational equilibrium that controls the population of a specific class of monomeric αSyn conformers, positively correlated with conditions known to promote the formation of aggregates. A new tool is thus made available to test directly the influence of mutations and pharmacological strategies on the conformational equilibrium of monomeric αSyn. PMID:18198943

Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide

NASA Astrophysics Data System (ADS)

Cohen, Samuel I. A.; Cukalevski, Risto; Michaels, Thomas C. T.; Šarić, Andela; Törnquist, Mattias; Vendruscolo, Michele; Dobson, Christopher M.; Buell, Alexander K.; Knowles, Tuomas P. J.; Linse, Sara

2018-05-01

Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.

Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide.

PubMed

Cohen, Samuel I A; Cukalevski, Risto; Michaels, Thomas C T; Šarić, Anđela; Törnquist, Mattias; Vendruscolo, Michele; Dobson, Christopher M; Buell, Alexander K; Knowles, Tuomas P J; Linse, Sara

2018-05-01

Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.

Micromechanical model of biphasic biomaterials with internal adhesion: Application to nanocellulose hydrogel composites.

PubMed

Bonilla, Mauricio R; Lopez-Sanchez, P; Gidley, M J; Stokes, J R

2016-01-01

The mechanical properties of hydrated biomaterials are non-recoverable upon unconfined compression if adhesion occurs between the structural components in the material upon fluid loss and apparent plastic behaviour. We explore these micromechanical phenomena by introducing an aggregation force and a critical yield pressure into the constitutive biphasic formulation for transversely isotropic tissues. The underlying hypothesis is that continual fluid pressure build-up during compression temporarily supresses aggregation. Once compression stops and the pressure falls below some critical value, internal aggregation occurs over a time scale comparable to the poroelastic time. We demonstrate this model by predicting the mechanical response of bacterial nanocellulose hydrogel composites, which are promising biomaterials and a structural mimetic for the plant cell wall. Cross-linking of cellulose by xyloglucan creates an extensional resistance and substantially increases the compressive modulus under large compression and densification. In comparison, incorporating non-crosslinking arabinoxylan into the hydrogel has little effect on its mechanics at the strain rates investigated. These results assist in elucidating the mechanical role of these polysaccharides in the complex plant cell wall structure. They also suggest xyloglucan is a suitable candidate to tailor the stiffness of nanocellulose hydrogels in biomaterial design, which includes modulating cell-adhesion in tissue engineering applications. The model and overall approach may be utilised to characterise and design a myriad of biomaterials and mammalian tissues, particularly those with a fibrillar structure. The mechanical properties of hydrated biomaterials can be non-recoverable upon compression due to increased adhesion occurring between the structural components in the material. Cellulose-hemicellulose composite hydrogels constitute a classical example of this phenomenon, since fibres can freely re-orient and adhere upon fluid loss to produce significant variations in the mechanical response to compression. Here, we model their micromechanics by introducing an aggregation force and a critical yield pressure into the constitutive formulation for transversely isotropic biphasic materials. The resulting model is easy to implement for routine characterization of this type of hydrated biomaterials through unconfined compression testing and produces physically meaningful and reproducible mechanical parameters. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Resolving the multifaceted mechanisms of the ferric chloride thrombosis model using an interdisciplinary microfluidic approach

PubMed Central

Ciciliano, Jordan C.; Sakurai, Yumiko; Myers, David R.; Fay, Meredith E.; Hechler, Beatrice; Meeks, Shannon; Li, Renhao; Dixon, J. Brandon; Lyon, L. Andrew; Gachet, Christian

2015-01-01

The mechanism of action of the widely used in vivo ferric chloride (FeCl3) thrombosis model remains poorly understood; although endothelial cell denudation is historically cited, a recent study refutes this and implicates a role for erythrocytes. Given the complexity of the in vivo environment, an in vitro reductionist approach is required to systematically isolate and analyze the biochemical, mass transfer, and biological phenomena that govern the system. To this end, we designed an “endothelial-ized” microfluidic device to introduce controlled FeCl3 concentrations to the molecular and cellular components of blood and vasculature. FeCl3 induces aggregation of all plasma proteins and blood cells, independent of endothelial cells, by colloidal chemistry principles: initial aggregation is due to binding of negatively charged blood components to positively charged iron, independent of biological receptor/ligand interactions. Full occlusion of the microchannel proceeds by conventional pathways, and can be attenuated by antithrombotic agents and loss-of-function proteins (as in IL4-R/Iba mice). As elevated FeCl3 concentrations overcome protective effects, the overlap between charge-based aggregation and clotting is a function of mass transfer. Our physiologically relevant in vitro system allows us to discern the multifaceted mechanism of FeCl3-induced thrombosis, thereby reconciling literature findings and cautioning researchers in using the FeCl3 model. PMID:25931587

Interaction and formation mechanism of binary complex between zein and propylene glycol alginate.

PubMed

Sun, Cuixia; Dai, Lei; Gao, Yanxiang

2017-02-10

The anti-solvent co-precipitation method was used to fabricate the zein-propylene glycol alginate (PGA) binary complex with different mass ratios of zein to PGA (20:1, 10:1, 5:1, 2:1 and 1:1) at pH 4.0. Results showed that attractive electrostatic interaction between zein and PGA occurred and negatively charged binary complex with large size and high turbidity was formed due to the charge neutralization. Hydrogen bonding and hydrophobic effects were involved in the interactions between zein and PGA, leading to the changed secondary structure and improved thermal stability of zein. Aggregates in the irregular shape with large size were obviously observed in the AFM images. PGA alone exhibited a fine filamentous network structure, while zein-PGA binary complex showed a rough branch-like pattern and the surface of "branch" was closely adsorbed by lots of spherical zein particles. Q in zein-PGA binary complex dispersions presented the improved photochemical and thermal stability. The potential mechanism of a two-step process was proposed to explain the formation of zein-PGA binary complexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetics of aggregation in charged nanoparticle solutions driven by different mechanisms

NASA Astrophysics Data System (ADS)

Abbas, S.; Yadav, I.; Kumar, Sugam; Aswal, V. K.; Kohlbrecher, J.

2017-05-01

The structure and kinetics during aggregation of anionic silica nanoparticles as induced through different mechanisms have been studied by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). Three different additives, namely an electrolyte (NaCl), cationic protein (lysozyme) and non-ionic surfactant (C12E10) were used to initiate nanoparticle aggregation. Electrolyte induced aggregation can be explained by DLVO interaction, whereas depletion interaction (non-DLVO interaction) is found responsible for nanoparticle aggregation in case of non-ionic surfactant. Unlike these two cases, strong electrostatic attraction between nanoparticle and oppositely charged protein results into protein-mediated nanoparticle aggregation. The electrolyte induced aggregation show quite slow aggregation rate whereas protein mediated as well as surfactant induced aggregation takes place almost instantaneously. The significant differences observed in the kinetics are explained based on range of interactions responsible for the aggregation. In spite of differences in mechanism and kinetics, the nanoparticle clusters are found to have similar fractal morphology (fractal dimension ˜ 2.5) in all the three cases.

Mechanisms behind overshoots in mean cluster size profiles in aggregation-breakup processes.

PubMed

Sadegh-Vaziri, Ramiar; Ludwig, Kristin; Sundmacher, Kai; Babler, Matthaus U

2018-05-26

Aggregation and breakup of small particles in stirred suspensions often shows an overshoot in the time evolution of the mean cluster size: Starting from a suspension of primary particles the mean cluster size first increases before going through a maximum beyond which a slow relaxation sets in. Such behavior was observed in various systems, including polymeric latices, inorganic colloids, asphaltenes, proteins, and, as shown by independent experiments in this work, in the flocculation of microalgae. This work aims at investigating possible mechanism to explain this phenomenon using detailed population balance modeling that incorporates refined rate models for aggregation and breakup of small particles in turbulence. Four mechanisms are considered: (1) restructuring, (2) decay of aggregate strength, (3) deposition of large clusters, and (4) primary particle aggregation where only aggregation events between clusters and primary particles are permitted. We show that all four mechanisms can lead to an overshoot in the mean size profile, while in contrast, aggregation and breakup alone lead to a monotonic, "S"-shaped size evolution profile. In order to distinguish between the different mechanisms simple protocols based on variations of the shear rate during the aggregation-breakup process are proposed. Copyright © 2018 Elsevier Inc. All rights reserved.

ERMO3/MVP1/GOLD36 Is Involved in a Cell Type-Specific Mechanism for Maintaining ER Morphology in Arabidopsis thaliana

PubMed Central

Nakano, Ryohei Thomas; Matsushima, Ryo; Nagano, Atsushi J.; Fukao, Yoichiro; Fujiwara, Masayuki; Kondo, Maki; Nishimura, Mikio; Hara-Nishimura, Ikuko

2012-01-01

The endoplasmic reticulum (ER) has a unique, network-like morphology. The ER structures are composed of tubules, cisternae, and three-way junctions. This morphology is highly conserved among eukaryotes, but the molecular mechanism that maintains ER morphology has not yet been elucidated. In addition, certain Brassicaceae plants develop a unique ER-derived organelle called the ER body. This organelle accumulates large amounts of PYK10, a β-glucosidase, but its physiological functions are still obscure. We aimed to identify a novel factor required for maintaining the morphology of the ER, including ER bodies, and employed a forward-genetic approach using transgenic Arabidopsis thaliana (GFP-h) with fluorescently-labeled ER. We isolated and investigated a mutant (designated endoplasmic reticulum morphology3, ermo3) with huge aggregates and abnormal punctate structures of ER. ERMO3 encodes a GDSL-lipase/esterase family protein, also known as MVP1. Here, we showed that, although ERMO3/MVP1/GOLD36 was expressed ubiquitously, the morphological defects of ermo3 were specifically seen in a certain type of cells where ER bodies developed. Coimmunoprecipitation analysis combined with mass spectrometry revealed that ERMO3/MVP1/GOLD36 interacts with the PYK10 complex, a huge protein complex that is thought to be important for ER body-related defense systems. We also found that the depletion of transcription factor NAI1, a master regulator for ER body formation, suppressed the formation of ER-aggregates in ermo3 cells, suggesting that NAI1 expression plays an important role in the abnormal aggregation of ER. Our results suggest that ERMO3/MVP1/GOLD36 is required for preventing ER and other organelles from abnormal aggregation and for maintaining proper ER morphology in a coordinated manner with NAI1. PMID:23155454

Morphology-Variable Aggregates Prepared from Cholesterol-Containing Amphiphilic Glycopolymers: Their Protein Recognition/Adsorption and Drug Delivery Applications

PubMed Central

Wang, Zhao; Luo, Ting; Cao, Amin; Sun, Jingjing; Jia, Lin

2018-01-01

In this study, a series of diblock glycopolymers, poly(6-O-methacryloyl-d-galactopyranose)-b-poly(6-cholesteryloxyhexyl methacrylate) (PMAgala-b-PMAChols), with cholesterol/galactose grafts were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and deprotection process. The glycopolymers could self-assemble into aggregates with various morphologies depending on cholesterol/galactose-containing block weight ratios, as determined by transmission electronic microscopy (TEM) and dynamic laser light scattering (DLS). In addition, the lectin (Ricinus communis agglutinin II, RCA120) recognition and bovine serum albumin (BSA) adsorption of the PMAgala-b-PMAChol aggregates were evaluated. The SK-Hep-1 tumor cell inhibition properties of the PMAgala-b-PMAChol/doxorubicin (DOX) complex aggregates were further examined in vitro. Results indicate that the PMAgala-b-PMAChol aggregates with various morphologies showed different interaction/recognition features with RCA120 and BSA. Spherical aggregates (d ≈ 92 nm) possessed the highest RCA120 recognition ability and lowest BSA protein adsorption. In addition, the DOX-loaded spherical complex aggregates exhibited a better tumor cell inhibition property than those of nanofibrous complex aggregates. The morphology-variable aggregates derived from the amphiphilic glycopolymers may serve as multifunctional biomaterials with biomolecular recognition and drug delivery features. PMID:29495614

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE PAGES

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke; ...

2015-12-29

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Formation and characterization of chitosan-protein particles with fractal whey protein aggregates.

PubMed

Ahmed, Khouloud Fekih; Aschi, Adel; Nicolai, Taco

2018-05-15

Hybrid protein-polysaccharide particles were formed by complexation of fractal whey protein aggregates and the cationic polysaccharide chitosan. The fractal aggregates were preformed by heating native whey protein isolate at pH 7 and subsequently mixed with chitosan at pH 3 where these proteins and polysaccharides don't interact with each other. Stable dispersions of protein-polysaccharide particles were formed spontaneously when the pH was gradually increased between 4.1 and 6.8, whereas in the absence of chitosan the fractal aggregates precipitated between pH 4.1 and 5.4. Potentiometric titration of the mixtures showed that deprotonation of both components was affected by complexation. With increasing pH, the size of the complexes increased sharply between pH 4.1. and pH 4.5, remained constant up to pH 5.6 and then increased again. A minimum amount of chitosan was needed to form stable complexes at pH 5.0 and the size of the complexes decreased with increasing chitosan concentration. Light scattering showed that the complexes were stable to dilution and had a self similar structure with a fractal dimensions close to two. The effect of changing the pH on the size and stability of the complexes was investigated. Suspensions of complexes of preformed whey protein aggregates and chitosan are more stable up to high pH (6.8) than complexes between native WPI and chitosan as reported in the literature. Copyright © 2018. Published by Elsevier B.V.

Mechanisms of amyloid formation revealed by solution NMR

PubMed Central

Karamanos, Theodoros K.; Kalverda, Arnout P.; Thompson, Gary S.; Radford, Sheena E.

2015-01-01

Amyloid fibrils are proteinaceous elongated aggregates involved in more than fifty human diseases. Recent advances in electron microscopy and solid state NMR have allowed the characterization of fibril structures to different extents of refinement. However, structural details about the mechanism of fibril formation remain relatively poorly defined. This is mainly due to the complex, heterogeneous and transient nature of the species responsible for assembly; properties that make them difficult to detect and characterize in structural detail using biophysical techniques. The ability of solution NMR spectroscopy to investigate exchange between multiple protein states, to characterize transient and low-population species, and to study high molecular weight assemblies, render NMR an invaluable technique for studies of amyloid assembly. In this article we review state-of-the-art solution NMR methods for investigations of: (a) protein dynamics that lead to the formation of aggregation-prone species; (b) amyloidogenic intrinsically disordered proteins; and (c) protein–protein interactions on pathway to fibril formation. Together, these topics highlight the power and potential of NMR to provide atomic level information about the molecular mechanisms of one of the most fascinating problems in structural biology. PMID:26282197

A Comprehensive Comparison of Multiparty Secure Additions with Differential Privacy

PubMed Central

Goryczka, Slawomir; Xiong, Li

2016-01-01

This paper considers the problem of secure data aggregation (mainly summation) in a distributed setting, while ensuring differential privacy of the result. We study secure multiparty addition protocols using well known security schemes: Shamir’s secret sharing, perturbation-based, and various encryptions. We supplement our study with our new enhanced encryption scheme EFT, which is efficient and fault tolerant. Differential privacy of the final result is achieved by either distributed Laplace or Geometric mechanism (respectively DLPA or DGPA), while approximated differential privacy is achieved by diluted mechanisms. Distributed random noise is generated collectively by all participants, which draw random variables from one of several distributions: Gamma, Gauss, Geometric, or their diluted versions. We introduce a new distributed privacy mechanism with noise drawn from the Laplace distribution, which achieves smaller redundant noise with efficiency. We compare complexity and security characteristics of the protocols with different differential privacy mechanisms and security schemes. More importantly, we implemented all protocols and present an experimental comparison on their performance and scalability in a real distributed environment. Based on the evaluations, we identify our security scheme and Laplace DLPA as the most efficient for secure distributed data aggregation with privacy. PMID:28919841

A Comprehensive Comparison of Multiparty Secure Additions with Differential Privacy.

PubMed

Goryczka, Slawomir; Xiong, Li

2017-01-01

This paper considers the problem of secure data aggregation (mainly summation) in a distributed setting, while ensuring differential privacy of the result. We study secure multiparty addition protocols using well known security schemes: Shamir's secret sharing, perturbation-based, and various encryptions. We supplement our study with our new enhanced encryption scheme EFT, which is efficient and fault tolerant. Differential privacy of the final result is achieved by either distributed Laplace or Geometric mechanism (respectively DLPA or DGPA), while approximated differential privacy is achieved by diluted mechanisms. Distributed random noise is generated collectively by all participants, which draw random variables from one of several distributions: Gamma, Gauss, Geometric, or their diluted versions. We introduce a new distributed privacy mechanism with noise drawn from the Laplace distribution, which achieves smaller redundant noise with efficiency. We compare complexity and security characteristics of the protocols with different differential privacy mechanisms and security schemes. More importantly, we implemented all protocols and present an experimental comparison on their performance and scalability in a real distributed environment. Based on the evaluations, we identify our security scheme and Laplace DLPA as the most efficient for secure distributed data aggregation with privacy.

Platelets, diabetes and myocardial ischemia/reperfusion injury.

PubMed

Russo, Isabella; Penna, Claudia; Musso, Tiziana; Popara, Jasmin; Alloatti, Giuseppe; Cavalot, Franco; Pagliaro, Pasquale

2017-05-31

Mechanisms underlying the pathogenesis of ischemia/reperfusion injury are particularly complex, multifactorial and highly interconnected. A complex and entangled interaction is also emerging between platelet function, antiplatelet drugs, coronary diseases and ischemia/reperfusion injury, especially in diabetic conditions. Here we briefly summarize features of antiplatelet therapy in type 2 diabetes (T2DM). We also treat the influence of T2DM on ischemia/reperfusion injury and how anti-platelet therapies affect post-ischemic myocardial damage through pleiotropic properties not related to their anti-aggregating effects. miRNA-based signature associated with T2DM and its cardiovascular disease complications are also briefly considered. Influence of anti-platelet therapies and different effects of healthy and diabetic platelets on ischemia/reperfusion injury need to be further clarified in order to enhance patient benefits from antiplatelet therapy and revascularization. Here we provide insight on the difficulty to reduce the cardiovascular risk in diabetic patients and report novel information on the cardioprotective role of widely used anti-aggregant drugs.

The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions.

PubMed

Liao, Jiahn-Haur; Wu, Tzu-Hua; Chen, Ming-Yi; Chen, Wei-Ting; Lu, Shou-Yun; Wang, Yi-Hsuan; Wang, Shao-Pin; Hsu, Yen-Min; Huang, Yi-Shiang; Huang, Zih-You; Lin, Yu-Ching; Chang, Ching-Ming; Huang, Fu-Yung; Wu, Shih-Hsiung

2015-12-04

In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO3(2-) and DCCM/SeO3(2-) complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions

NASA Astrophysics Data System (ADS)

Li, Jianguo; Garg, Manju; Shah, Dhawal; Rajagopalan, Raj

2010-08-01

Experiments hold intriguing, circumstantial clues to the mechanisms behind arginine-mediated solubilization of small organic drugs and suppression of protein aggregation driven by hydrophobic or aromatic associations, but how exactly arginine's molecular structure and interactions contribute to its function remains unclear since attention has focused so far on the thermodynamics of the preferential exclusion or binding of arginine. Here, we examine, through molecular dynamics simulations, how arginine solubilizes nanoscale particles with hydrophobic surfaces or aromatic-ring-type surface interactions. We show that preferential, hydrophobic, and dispersion interactions of arginine's guanidinium group with the particles lead to a surfactant-like behavior of arginine around the particles and to a solvation layer with a protective polar mask creating a hydrophilic shell. Additionally, arginine-arginine association around the solvation layer further prevents aggregative contacts. The results shed some light on the mechanistic basis of arginine's function as a suppressant of protein aggregation, although the complex energy landscapes and kinetic pathways of aggregation are protein-dependent and pose formidable challenges to developing comprehensive mechanistic pictures. Our results suggest arginine's mode of interaction with hydrophobic patches and aromatic residues could reduce aggregation-prone intermediate states of proteins and shield protein-protein aggregative contacts. The approach used here offers a systematic way of exploring implications of other amino acid/excipient interactions by studying interactions of the excipient with particles grafted with amino acids.

E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I

PubMed Central

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T.

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation’s effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases. PMID:24023838

Beneficial characteristics of mechanically functional amyloid fibrils evolutionarily preserved in natural adhesives

NASA Astrophysics Data System (ADS)

Mostaert, Anika S.; Jarvis, Suzanne P.

2007-01-01

While biological systems are notorious for their complexity, nature sometimes displays mechanisms that are elegant in their simplicity. We have recently identified such a mechanism at work to enhance the mechanical properties of certain natural adhesives. The mechanism is simple because it utilizes a non-specific protein folding and subsequent aggregation process, now thought to be generic for any polypeptide under appropriate conditions. This non-specific folding forms proteinaceous crossed β-sheet amyloid fibrils, which are usually associated with neurodegenerative diseases. Here we show evidence for the beneficial mechanical characteristics of these fibrils discovered in natural adhesives. We suggest that amyloid protein quaternary structures should be considered as a possible generic mechanism for mechanical strength in a range of natural adhesives and other natural materials due to their many beneficial mechanical features and apparent ease of self-assembly.

Activation of the DnaK-ClpB Complex is Regulated by the Properties of the Bound Substrate.

PubMed

Fernández-Higuero, Jose Angel; Aguado, Alejandra; Perales-Calvo, Judit; Moro, Fernando; Muga, Arturo

2018-04-11

The chaperone ClpB in bacteria is responsible for the reactivation of aggregated proteins in collaboration with the DnaK system. Association of these chaperones at the aggregate surface stimulates ATP hydrolysis, which mediates substrate remodeling. However, a question that remains unanswered is whether the bichaperone complex can be selectively activated by substrates that require remodeling. We find that large aggregates or bulky, native-like substrates activates the complex, whereas a smaller, permanently unfolded protein or extended, short peptides fail to stimulate it. Our data also indicate that ClpB interacts differently with DnaK in the presence of aggregates or small peptides, displaying a higher affinity for aggregate-bound DnaK, and that DnaK-ClpB collaboration requires the coupled ATPase-dependent remodeling activities of both chaperones. Complex stimulation is mediated by residues at the β subdomain of DnaK substrate binding domain, which become accessible to the disaggregase when the lid is allosterically detached from the β subdomain. Complex activation also requires an active NBD2 and the integrity of the M domain-ring of ClpB. Disruption of the M-domain ring allows the unproductive stimulation of the DnaK-ClpB complex in solution. The ability of the DnaK-ClpB complex to discrimínate different substrate proteins might allow its activation when client proteins require remodeling.

Sensor Abstractions to Support Many-Robot Systems

DTIC Science & Technology

1993-04-01

the behaviors of the social insects: ants, bees, and termites ; the observed aggregate behaviors exhibit a greater complexity, while the individual...applicability -’f" togies from biology (hjrdirg, ec!"x’-oig, iiununc system and pheromone mechanisms) and physics (entropy, temperature, pressure...in [17-19]. Pheromones provide an important example of animals arranging their environment to, for example, help moths find mates, or to help a colony

The ribosome-associated complex antagonizes prion formation in yeast.

PubMed

Amor, Alvaro J; Castanzo, Dominic T; Delany, Sean P; Selechnik, Daniel M; van Ooy, Alex; Cameron, Dale M

2015-01-01

The number of known fungal proteins capable of switching between alternative stable conformations is steadily increasing, suggesting that a prion-like mechanism may be broadly utilized as a means to propagate altered cellular states. To gain insight into the mechanisms by which cells regulate prion formation and toxicity we examined the role of the yeast ribosome-associated complex (RAC) in modulating both the formation of the [PSI(+)] prion - an alternative conformer of Sup35 protein - and the toxicity of aggregation-prone polypeptides. The Hsp40 RAC chaperone Zuo1 anchors the RAC to ribosomes and stimulates the ATPase activity of the Hsp70 chaperone Ssb. We found that cells lacking Zuo1 are sensitive to over-expression of some aggregation-prone proteins, including the Sup35 prion domain, suggesting that co-translational protein misfolding increases in Δzuo1 strains. Consistent with this finding, Δzuo1 cells exhibit higher frequencies of spontaneous and induced prion formation. Cells expressing mutant forms of Zuo1 lacking either a C-terminal charged region required for ribosome association, or the J-domain responsible for Ssb ATPase stimulation, exhibit similarly high frequencies of prion formation. Our findings are consistent with a role for the RAC in chaperoning nascent Sup35 to regulate folding of the N-terminal prion domain as it emerges from the ribosome.

Molecular simulations of micellar aggregation of polysorbate 20 ester fractions and their interaction with N-phenyl-1-naphthylamine dye.

PubMed

Lapelosa, Mauro; Patapoff, Thomas W; Zarraga, Isidro E

2016-06-01

Micellar aggregation behavior of polysorbate 20 (PS20) has generated significant interest because of the wide use of PS20 as a surfactant to minimize protein surface adsorption and mitigate protein aggregation. Thus, there is a need for better molecular understanding of what drives the biophysical behavior of PS20 in solution. We observe that a complex amphipathic PS20 molecule, which contains both hydrophobic tail and relatively large hydrophilic head, self-associates strongly within the course of a molecular dynamics simulation performed with a fully atomistic representation of the molecule and an explicit water solvent model. The in silico behavior is consistent with micellar models of PS20 in solution. The dynamics of this self-association is rather complex involving both internal reorganization of the molecule and diffusion to form stable micelle-like aggregates. The micellar aggregates of PS20 are long-lived and are formed by the balance between the large hydrophobic interactions associated with the aliphatic tail of PS20, and the steric repulsion of the hydrophilic sorbitan head structure. In the present work, molecular models of PS20 that represent naturally occurring PS20 fractions were produced and characterized in silico. The study investigated the monoester and diester fractions: PS20M, and PS20D. These fractions present differences in the strength of their hydrophobic effect, which influences the aggregation behavior. Adaptive biasing force (ABF) simulations were carried out with the PS20M and PS20D molecular constructs to calculate the free energy of their pairwise interaction. The free energy barrier for the dissociation is higher for PS20D compared with PS20M. The results show that hydrogen bonds can form when head groups are in close proximity, such as in the PS20 aggregate assembly, and the free energy of interaction can be used to predict the morphology of the micellar aggregate for the different PS20 fractions. We were also able to simulate PS20 in the presence of N-phenyl-1-naphthylamine (NPN) to study the solution behavior of the hydrophobic molecule and of the mechanism in which it is sequestered in the hydrophobic core of the PS20 micellar aggregate. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Crucial HSP70 co–chaperone complex unlocks metazoan protein disaggregation

PubMed Central

Nillegoda, Nadinath B.; Kirstein, Janine; Szlachcic, Anna; Berynskyy, Mykhaylo; Stank, Antonia; Stengel, Florian; Arnsburg, Kristin; Gao, Xuechao; Scior, Annika; Aebersold, Ruedi; Guilbride, D. Lys; Wade, Rebecca C.; Morimoto, Richard I.; Mayer, Matthias P.; Bukau, Bernd

2016-01-01

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states1,2. Healthy metazoan cells effectively eliminate intracellular protein aggregates3,4, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems5,6, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro4,7. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control. PMID:26245380

Particle size effect and the mechanism of hematite reduction by the outer membrane cytochrome OmcA of Shewanella oneidensis MR-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Juan; Pearce, Carolyn I.; Shi, Liang

The cycling of iron at the Earth’s near surface is profoundly influenced by dissimilatory metal reducing microorganisms, and many studies have focused on unraveling electron transfer mechanisms between these bacteria and Fe(III)-(oxyhydr)oxides. However, these efforts have been complicated by the fact that these minerals often occur in the micro- to nanosize regime, and in relevant natural environments as well as in the laboratory are subject to aggregation. The nature of the physical interface between the cellular envelope, the outer-membrane cytochromes responsible for facilitating the interfacial electron transfer step, and these complex mineral particulates is thus difficult to probe. Previous studiesmore » using whole cells have reported reduction rates that do not correlate with particle size. In the present study we isolate the interaction between the decaheme outer-membrane cytochrome OmcA of Shewanella oneidensis and nanoparticulate hematite, examining the reduction rate as a function of particle size and reaction products through detailed characterization of the electron balance and the structure and valence of iron at particle surfaces. By comparison with abiotic reduction via the smaller molecule ascorbic acid, we show that the reduction rate is systematically controlled by the sterically accessible interfacial contact area between OmcA and hematite in particle aggregates; rates increase once pore throat sizes in aggregates become as large as OmcA. Simultaneous measure of OmcA oxidation against Fe(II) release shows a ratio of 1:10, consistent with a cascade OmcA oxidation mechanism heme by heme. X-ray absorption spectroscopies reveal incipient magnetite on the reacted surfaces of the hematite nanoparticles after reaction. The collective findings establish the importance of accessibility of physical contact between the terminal reductases and iron oxide surfaces, and through apparent consistency of observations help reconcile behavior reported at the larger more complex scale of whole cell studies.« less

Particle size effect and the mechanism of hematite reduction by the outer membrane cytochrome OmcA of Shewanella oneidensis MR-1

NASA Astrophysics Data System (ADS)

Liu, Juan; Pearce, Carolyn I.; Shi, Liang; Wang, Zheming; Shi, Zhi; Arenholz, Elke; Rosso, Kevin M.

2016-11-01

The cycling of iron at the Earth's near surface is profoundly influenced by dissimilatory metal reducing microorganisms, and many studies have focused on unraveling electron transfer mechanisms between these bacteria and Fe(III)-(oxyhydr)oxides. However, these efforts have been complicated by the fact that these minerals often occur in the micro- to nanosize regime, and in relevant natural environments as well as in the laboratory are subject to aggregation. The nature of the physical interface between the cellular envelope, the outer-membrane cytochromes responsible for facilitating the interfacial electron transfer step, and these complex mineral particulates is thus difficult to probe. Previous studies using whole cells have reported reduction rates that do not correlate with particle size. In the present study we isolate the interaction between the decaheme outer-membrane cytochrome OmcA of Shewanella oneidensis and nanoparticulate hematite, examining the reduction rate as a function of particle size and reaction products through detailed characterization of the electron balance and the structure and valence of iron at particle surfaces. By comparison with abiotic reduction via the smaller molecule ascorbic acid, we show that the reduction rate is systematically controlled by the sterically accessible interfacial contact area between OmcA and hematite in particle aggregates; rates increase once pore throat sizes in aggregates become as large as OmcA. Simultaneous measure of OmcA oxidation against Fe(II) release shows a ratio of 1:10, consistent with a cascade OmcA oxidation mechanism heme by heme. X-ray absorption spectroscopies reveal incipient magnetite on the reacted surfaces of the hematite nanoparticles after reaction. The collective findings establish the importance of accessibility of physical contact between the terminal reductases and iron oxide surfaces, and through apparent consistency of observations help reconcile behavior reported at the larger more complex scale of whole cell studies.

Nanoscale assembly processes revealed in the nacroprismatic transition zone of Pinna nobilis mollusc shells

PubMed Central

Hovden, Robert; Wolf, Stephan E.; Holtz, Megan E.; Marin, Frédéric; Muller, David A.; Estroff, Lara A.

2015-01-01

Intricate biomineralization processes in molluscs engineer hierarchical structures with meso-, nano- and atomic architectures that give the final composite material exceptional mechanical strength and optical iridescence on the macroscale. This multiscale biological assembly inspires new synthetic routes to complex materials. Our investigation of the prism–nacre interface reveals nanoscale details governing the onset of nacre formation using high-resolution scanning transmission electron microscopy. A wedge-polishing technique provides unprecedented, large-area specimens required to span the entire interface. Within this region, we find a transition from nanofibrillar aggregation to irregular early-nacre layers, to well-ordered mature nacre suggesting the assembly process is driven by aggregation of nanoparticles (∼50–80 nm) within an organic matrix that arrange in fibre-like polycrystalline configurations. The particle number increases successively and, when critical packing is reached, they merge into early-nacre platelets. These results give new insights into nacre formation and particle-accretion mechanisms that may be common to many calcareous biominerals. PMID:26631940

Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity

PubMed Central

Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

2012-01-01

Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity. PMID:22955885

Microemulsions and Aggregation Formation in Extraction Processes for Used Nuclear Fuel: Thermodynamic and Structural Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilsson, Mikael

Advanced nuclear fuel cycles rely on successful chemical separation of various elements in the used fuel. Numerous solvent extraction (SX) processes have been developed for the recovery and purification of metal ions from this used material. However, the predictability of process operations has been challenged by the lack of a fundamental understanding of the chemical interactions in several of these separation systems. For example, gaps in the thermodynamic description of the mechanism and the complexes formed will make predictions very challenging. Recent studies of certain extraction systems under development and a number of more established SX processes have suggested thatmore » aggregate formation in the organic phase results in a transformation of its selectivity and efficiency. Aggregation phenomena have consistently been interfering in SX process development, and have, over the years, become synonymous with an undesirable effect that must be prevented. This multiyear, multicollaborative research effort was carried out to study solvation and self-organization in non-aqueous solutions at conditions promoting aggregation phenomena. Our approach to this challenging topic was to investigate extraction systems comprising more than one extraction reagent where synergy of the metal ion could be observed. These systems were probed for the existence of stable microemulsions in the organic phase, and a number of high-end characterization tools were employed to elucidate the role of the aggregates in metal ion extraction. The ultimate goal was to find connections between synergy of metal ion extraction and reverse micellar formation. Our main accomplishment for this project was the expansion of the understanding of metal ion complexation in the extraction system combining tributyl phosphate (TBP) and dibutyl phosphoric acid (HDBP). We have found that for this system no direct correlation exists for the metal ion extraction and the formation of aggregates, meaning that the metal ion is not solubilized in a reverse micelle core. Rather we have found solid evidence that the metal ions are extracted and coordinated by the organic ligands as suggested by classic SX theories. However, we have challenged the existence of mixed complexes that have been suggested to exist in this particular extraction system. Most importantly we have generated a wealth of information and trained students on important lab techniques and strengthened the collaboration between the DOE national laboratories and US educational institution involved in this work.« less

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells.

PubMed

Guo, Na; Zhang, Kui; Lv, Minghua; Miao, Jinlin; Chen, Zhinan; Zhu, Ping

2015-02-01

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ethanol reduces amyloid aggregation in vitro and prevents toxicity in cell lines.

PubMed

Ormeño, David; Romero, Fernando; López-Fenner, Julio; Avila, Andres; Martínez-Torres, Ataulfo; Parodi, Jorge

2013-01-01

Alzheimer's disease (AD) alters cognitive functions. A mixture of soluble β-amyloid aggregates (Aβ) are known to act as toxic agents. It has been suggested that moderate alcohol intake reduces the development of neurodegenerative diseases, but the molecular mechanisms leading to this type of prevention have been elusive. We show the ethanol effect in the generation of complex Aβ in vitro and the impact on the viability of two cell lines. The effect of ethanol on the kinetics of β-amyloid aggregation in vitro was assessed by turbimetry. Soluble- and ethanol-treated β-amyloid were added to the cell lines HEK and PC-12 to compare their effects on metabolic activity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, we used molecular modeling to assess the impact of exposure to ethanol on the structure of β-amyloid. Exposure to soluble β-amyloid was toxic to both cell lines; however, exposing the cells to β-amyloid aggregated in 10 mmol ethanol prevented the effect. In silico modeling suggested that ethanol alters the dynamics for assembling Aβ by disrupting a critical salt bridge between residues Asp 23 and Lys 28, required for amyloid dimerization. Thus, ethanol prevented the formation of complex short (∼100 nm) Aβ, which are related to higher cell toxicity. Ethanol prevents the formation of stable Aβ dimers in vitro, thus protecting the cells maintained in culture. Accordingly, in silico modelling predicts that soluble β-amyloid molecules do not form stable multimers when exposed to ethanol. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Calcium movements during pigment aggregation in freshwater shrimp chromatophores.

PubMed

Ribeiro, Márcia; McNamara, John Campbell

2007-02-01

Pigment granule migration within crustacean chromatophores provides an excellent model with which to investigate cytoplasmic movements, given the antagonistic, neurosecretory peptide regulation of granule translocation, and the absence of innervation in these large, brightly colored cells. Red pigment-concentrating hormone (RPCH) induces pigment aggregation in shrimp chromatophores via an increase in intracellular Ca2+; however, how this increase is brought about is not known. To examine the putative Ca2+ movements leading to pigment translocation in red, ovarian chromatophores of the freshwater shrimp, Macrobrachium olfersii, this study manipulates intra- and extracellular Ca2+ employing ER Ca2+-ATPase inhibitors, ryanodine-sensitive, ER Ca2+ channel blockers, and EDTA/EGTA-buffered A23187/Ca2+-containing salines. Our findings reveal that during pigment aggregation, cytosolic Ca2+ apparently increases from an intracellular source, the abundant SER, loaded by the SERCA and released through ryanodine-sensitive receptor/channels, triggered by capacitative calcium influx and/or calcium-induced calcium release mechanisms. Aggregation also depends on external calcium, which may modulate RPCH/receptor coupling. Such calcium-regulated pigment movements form the basis of a complex system of chromatic adaptation, which confers selective advantages like camouflage and protection against ultra-violet radiation to this palaemonid shrimp.

Replica exchange molecular dynamics simulation of cross-fibrillation of IAPP and PrP106-126.

PubMed

Chua, Khi Pin; Chew, Lock Yue; Mu, Yuguang

2016-08-01

Aggregation of proteins into amyloid is the central hallmark of a number of protein diseases. Most studies were carried out on the aggregation between proteins of similar species. However, it was observed that some patients with certain protein disease can easily acquire another unrelated protein disease. As such, it is also important to examine aggregation between proteins of different species. Usually aggregation between proteins of the same species can be attributed to the similarity between their respective amino acid sequences. In this article, we were motivated by an experimental study of aggregation between amylin (Islet Amyloid Polypeptide, IAPP) and prion106-126 (PrP106-126) fragment (JACS, 2013, 135, 13582-9). It was found that the two non-homologous peptides can aggregate quickly to form fibrils in the presence of negatively charged lipid bilayer. We attempted to elucidate the molecular mechanism of the early stage of dimerization of these two peptides through extensive replica exchange molecular dynamics simulations. Conformations consisting of various degrees of β-sheets structures, both intra-chain and inter-chain, were found in the simulations. The conformations of the aggregated complex are very diverse, which suggests that the cross-species fibrils formed between the two proteins are highly polymorphic. The driving forces are mainly hydrophobic interactions, including aromatic-aliphatic interactions. The palindromic region of PrP106-126 and SNNFGAIL region of IAPP were found to play important roles in the interaction. Our study sheds insight into the exciting research of protein cross-fibrillation. Proteins 2016; 84:1134-1146. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural, Optical, and Photocatalytic Properties of Quasi-One-Dimensional Nanocrystalline ZnO, ZnOC:nC Composites, and C-doped ZnO

NASA Astrophysics Data System (ADS)

Shalaeva, E. V.; Gyrdasova, O. I.; Krasilnikov, V. N.; Melkozerova, M. A.; Baklanova, I. V.; Buldakova, L. Yu.

Various thermolysis rotes of zinc glicolate complexes are considered for the synthesis of quasi-one-dimensional nanostructured aggregates ZnO and Zn-O-C used as photocatalysts. Structural features of quasi-one-dimensional aggregates Zn-O-C and ZnO are investigated in detail. Transmission electron microscopy, Raman spectroscopy, and electron paramagnetic resonance spectroscopy methods demonstrate that the aggregates Zn-O-C have either composite structure (ZnO crystallites in amorphous carbon matrix) or a C-doped ZnO single-phase structure depending on heat treatment conditions, and that all the aggregates exhibit as a rule a tubular morphology, a nanocrystalline structure with a high specific surface area, and a high concentration of singly charged oxygen vacancies. The mechanism of the nanocrystalline structure formation is discussed and the effect of thermolysis condition on the formation of the textured structure of aggregates is investigated. The results of examination of the photocatalytic and optical absorption properties of the synthesized aggregates are presented. The photocatalytic activity for the hydroquinone oxidation reaction under ultraviolet and visible light increases in the series: the reference ZnO powder, quasi-one-dimensional ZnO, quasi-one-dimensional aggregates C-doped ZnO, and this tendency correlates with the reduction of the optical gap width. As a result of our studies, we have arrived at an important conclusion that thermal treatment of ZnO:nC composites allows a C-doped ZnO with high catalytic activity. This increasing photoactivity of C-doped ZnO aggregates is attributed to the optimal specific surface area and electron-energy spectrum restructuring to be produced owing to the presence of singly charged oxygen vacancies and carbon dissolved in the ZnO lattice.

Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

PubMed

Pradhan, Mohan R; Pal, Arumay; Hu, Zhongqiao; Kannan, Srinivasaraghavan; Chee Keong, Kwoh; Lane, David P; Verma, Chandra S

2016-02-01

Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. © 2015 Wiley Periodicals, Inc.

Measurement of net electric charge and dipole moment of dust aggregates in a complex plasma.

PubMed

Yousefi, Razieh; Davis, Allen B; Carmona-Reyes, Jorge; Matthews, Lorin S; Hyde, Truell W

2014-09-01

Understanding the agglomeration of dust particles in complex plasmas requires knowledge of basic properties such as the net electrostatic charge and dipole moment of the dust. In this study, dust aggregates are formed from gold-coated mono-disperse spherical melamine-formaldehyde monomers in a radiofrequency (rf) argon discharge plasma. The behavior of observed dust aggregates is analyzed both by studying the particle trajectories and by employing computer models examining three-dimensional structures of aggregates and their interactions and rotations as induced by torques arising from their dipole moments. These allow the basic characteristics of the dust aggregates, such as the electrostatic charge and dipole moment, as well as the external electric field, to be determined. It is shown that the experimental results support the predicted values from computer models for aggregates in these environments.

Optical network scaling: roles of spectral and spatial aggregation.

PubMed

Arık, Sercan Ö; Ho, Keang-Po; Kahn, Joseph M

2014-12-01

As the bit rates of routed data streams exceed the throughput of single wavelength-division multiplexing channels, spectral and spatial traffic aggregation become essential for optical network scaling. These aggregation techniques reduce network routing complexity by increasing spectral efficiency to decrease the number of fibers, and by increasing switching granularity to decrease the number of switching components. Spectral aggregation yields a modest decrease in the number of fibers but a substantial decrease in the number of switching components. Spatial aggregation yields a substantial decrease in both the number of fibers and the number of switching components. To quantify routing complexity reduction, we analyze the number of multi-cast and wavelength-selective switches required in a colorless, directionless and contentionless reconfigurable optical add-drop multiplexer architecture. Traffic aggregation has two potential drawbacks: reduced routing power and increased switching component size.

Inhibition of copper-mediated aggregation of human γD-crystallin by Schiff bases.

PubMed

Chauhan, Priyanka; Muralidharan, Sai Brinda; Velappan, Anand Babu; Datta, Dhrubajyoti; Pratihar, Sanjay; Debnath, Joy; Ghosh, Kalyan Sundar

2017-06-01

Protein aggregation, due to the imbalance in the concentration of Cu 2+ and Zn 2+ ions is found to be allied with various physiological disorders. Copper is known to promote the oxidative damage of β/γ-crystallins in aged eye lens and causes their aggregation leading to cataract. Therefore, synthesis of a small-molecule 'chelator' for Cu 2+ with complementary antioxidant effect will find potential applications against aggregation of β/γ-crystallins. In this paper, we have reported the synthesis of different Schiff bases and studied their Cu 2+ complexation ability (using UV-Vis, FT-IR and ESI-MS) and antioxidant activity. Further based on their copper complexation efficiency, Schiff bases were used to inhibit Cu 2+ -mediated aggregation of recombinant human γD-crystallin (HGD) and β/γ-crystallins (isolated from cataractous human eye lens). Among these synthesized molecules, compound 8 at a concentration of 100 μM had shown ~95% inhibition of copper (100 μM)-induced aggregation. Compound 8 also showed a positive cooperative effect at a concentration of 5-15 μM on the inhibitory activity of human αA-crystallin (HAA) during Cu 2+ -induced aggregation of HGD. It eventually inhibited the aggregation process by additional ~20%. However, ~50% inhibition of copper-mediated aggregation of β/γ-crystallins (isolated from cataractous human eye lens) was recorded by compound 8 (100 μM). Although the reductive aminated products of the imines showed better antioxidant activity due to their lower copper complexing ability, they were found to be non-effective against Cu 2+ -mediated aggregation of HGD.

Secure and effective gene delivery system of plasmid DNA coated by polynucleotide.

PubMed

Kodama, Yukinobu; Ohkubo, Chikako; Kurosaki, Tomoaki; Egashira, Kanoko; Sato, Kayoko; Fumoto, Shintaro; Nishida, Koyo; Higuchi, Norihide; Kitahara, Takashi; Nakamura, Tadahiro; Sasaki, Hitoshi

2015-01-01

Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system.

Study of the aggregation mechanism of polyglutamine peptides using replica exchange molecular dynamics simulations.

PubMed

Nakano, Miki; Ebina, Kuniyoshi; Tanaka, Shigenori

2013-04-01

Polyglutamine (polyQ, a peptide) with an abnormal repeat length is the causative agent of polyQ diseases, such as Huntington's disease. Although glutamine is a polar residue, polyQ peptides form insoluble aggregates in water, and the mechanism for this aggregation is still unclear. To elucidate the detailed mechanism for the nucleation and aggregation of polyQ peptides, replica exchange molecular dynamics simulations were performed for monomers and dimers of polyQ peptides with several chain lengths. Furthermore, to determine how the aggregation mechanism of polyQ differs from those of other peptides, we compared the results for polyQ with those of polyasparagine and polyleucine. The energy barrier between the monomeric and dimeric states of polyQ was found to be relatively low, and it was observed that polyQ dimers strongly favor the formation of antiparallel β-sheet structures. We also found a characteristic behavior of the monomeric polyQ peptide: a turn at the eighth residue is always present, even when the chain length is varied. We previously showed that a structure including more than two sets of β-turns is stable, so a long monomeric polyQ chain can act as an aggregation nucleus by forming several pairs of antiparallel β-sheet structures within a single chain. Since the aggregation of polyQ peptides has some features in common with an amyloid fibril, our results shed light on the mechanism for the aggregation of polyQ peptides as well as the mechanism for the formation of general amyloid fibrils, which cause the onset of amyloid diseases.

Interplay between membrane elasticity and active cytoskeleton forces regulates the aggregation dynamics of the immunological synapse

NASA Astrophysics Data System (ADS)

Dharan, Nadiv; Farago, Oded

Adhesion between a T cell and an antigen presenting cell is achieved by TCR-pMHC and LFA1-ICAM1 protein complexes. These segregate to form a special pattern, known as the immunological synapse (IS), consisting of a central quasi-circular domain of TCR-pMHC bonds surrounded by a peripheral domain of LFA1-ICAM1 complexes. Insights gained from imaging studies had led to the conclusion that the formation of the central adhesion domain in the IS is driven by active (ATP-driven) mechanisms. Recent studies, however, suggested that passive (thermodynamic) mechanisms may also play an important role in this process. Here, we present a simple physical model, taking into account the membrane-mediated thermodynamic attraction between the TCR-pMHC bonds and the effective forces that they experience due to ATP-driven actin retrograde flow and transport by dynein motor proteins. Monte Carlo simulations of the model exhibit a good spatio-temporal agreement with the experimentally observed pattern evolution of the TCR-pMHC microclusters. The agreement is lost when one of the aggregation mechanisms is "muted", which helps to identify the respective roles in the process. We conclude that actin retrograde flow drives the centripetal motion of TCR-pMHC bonds, while the membrane-mediated interactions facilitate microcluster formation and growth. In the absence of dynein motors, the system evolves into a ring-shaped pattern, which highlights the role of dynein motors in the formation of the final concentric pattern. The interplay between the passive and active mechanisms regulates the rate of the accumulation process, which in the absence of one them proceeds either too quickly or slowly.

Quercetagetin-Loaded Zein-Propylene Glycol Alginate Ternary Composite Particles Induced by Calcium Ions: Structure Characterization and Formation Mechanism.

PubMed

Sun, Cuixia; Wei, Yang; Li, Ruirui; Dai, Lei; Gao, Yanxiang

2017-05-17

The complexation of zein and propylene glycol alginate (PGA) was confirmed to improve the entrapment efficiency and loading capacity of quercetagetin (Q) in our previous study. The present work focused on the influence and induction mechanism of calcium ions on structures of Q-loaded zein-PGA ternary composite particles. The incorporation of Ca 2+ resulted in the formation of aggregates with a large dimension between zein particles, led to obvious conformational, secondary, and tertiary structural changes of zein, and caused the disappearance of crystalline structure of zein. PGA exhibited a fine filamentous network structure and became much thicker and stronger in the presence of Ca 2+ . The presence of Q promoted the affinity and binding capacity of Ca 2+ to zein and PGA. An interwoven network structure with enhanced firmness and density was observed in Q-loaded zein-PGA composite particles, leading to improved thermal stability. Three potential mechanisms were proposed to explain the structural characteristics induced by Ca 2+ , including particle-particle collision for zein particles, chain-chain association for PGA molecules, and simultaneous cross-linking coupled with aggregating for Q-loaded zein-PGA composite particles.

Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krogstad, Daniel V.; Wang, Dongbo; Lin-Gibson, Sheng

Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transformmore » infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.« less

Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions

PubMed Central

Vest, Rebekah S.; O’Leary, Heather; Bayer, K. Ulrich

2009-01-01

CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca2+ (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement for nucleotide binding but not auto-phosphorylation also for extra-synaptic clustering within neurons. These results clarify a previously apparent paradox in the nucleotide and phosphorylation requirement of aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T-site interaction. PMID:19840793

Activity-driven changes in the mechanical properties of fire ant aggregations

NASA Astrophysics Data System (ADS)

Tennenbaum, Michael; Fernandez-Nieves, Alberto

2017-11-01

Fire ant aggregations are active materials composed of individual constituents that are able to transform internal energy into work. We find using rheology and direct visualization that the aggregation undergoes activity cycles that affect the mechanical properties of the system. When the activity is high, the aggregation approximately equally stores and dissipates energy, it is more homogeneous, and exerts a high outward force. When the activity is low, the aggregation is predominantly elastic, it is more heterogeneous, and it exerts a small outward force. We rationalize our results using a simple kinetic model where the number of active ants within the aggregation is the essential quantity.

Study on Excitation-triggered Damage Mechanism in Perilous Rock

NASA Astrophysics Data System (ADS)

Chen, Hongkai; Wang, Shengjuan

2017-12-01

Chain collapse is easy to happen for perilous rock aggregate locating on steep high slope, and one of the key scientific problems is the damage mechanism of perilous rock under excitation action at perilous rock rupture. This paper studies excitation-triggered damage mechanism in perilous rock by wave mechanics, which gives three conclusions. Firstly, when only the normal incidence attenuation spread of excitation wave is considered, while the energy loss is ignored for excitation wave to spread in perilous rock aggregate, the paper establishes one method to calculate peak velocity when excitation wave passes through boundary between any two perilous rock blocks in perilous rock aggregate. Secondly, following by Sweden and Canmet criteria, the paper provides one wave velocity criterion for excitation-triggered damage in the aggregate. Thirdly, assuming double parameters of volume strain of cracks or fissures in rock meet the Weibull distribution, one method to estimate micro-fissure in excitation-triggered damage zone in perilous rock aggregate is established. The studies solve the mechanical description problem for excitation-triggered damage in perilous rock, which is valuable in studies on profoundly rupture mechanism.

Relaxation times and modes of disturbed aggregate distribution in micellar solutions with fusion and fission of micelles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakharov, Anatoly I.; Adzhemyan, Loran Ts.; Shchekin, Alexander K., E-mail: akshch@list.ru

2015-09-28

We have performed direct numerical calculations of the kinetics of relaxation in the system of surfactant spherical micelles under joint action of the molecular mechanism with capture and emission of individual surfactant molecules by molecular aggregates and the mechanism of fusion and fission of the aggregates. As a basis, we have taken the difference equations of aggregation and fragmentation in the form of the generalized kinetic Smoluchowski equations for aggregate concentrations. The calculations have been made with using the droplet model of molecular surfactant aggregates and two modified Smoluchowski models for the coefficients of aggregate-monomer and aggregate-aggregate fusions which takemore » into account the effects of the aggregate size and presence of hydrophobic spots on the aggregate surface. A full set of relaxation times and corresponding relaxation modes for nonequilibrium aggregate distribution in the aggregation number has been found. The dependencies of these relaxation times and modes on the total concentration of surfactant in the solution and the special parameter controlling the probability of fusion in collisions of micelles with other micelles have been studied.« less

Enrichment Ratio and Aggregate Stability Dynamics in Intensely Managed Landscapes

NASA Astrophysics Data System (ADS)

Wacha, K.; Papanicolaou, T.; Filley, T. R.; Hou, T.; Abban, B. K.; Wilson, C. G.; Boys, J.

2015-12-01

Challenges in understanding the soil carbon dynamics within intensely managed landscapes (IMLs), found throughout much the US Midwest, is highly complex due to the presence of heterogeneous landscape features and properties, as well as a mosaic of physical and biogeochemical processes occurring at different time scales. In addition, rainfall events exacerbate the effects of tillage by the impact of raindrops, which break down aggregates that encase carbon and dislodge and entrain soil particles and aggregates along the downslope. The redistribution of soil and carbon can have huge implications on biogeochemical cycling and overall carbon budgeting. In this study, we provide some rare field data on the mechanisms impacting aggregate stability, enrichment ratio values to estimate fluxes of carbon, as well as lignin chemistry to see influences on oxidation/mineralization rates. Rainfall simulation experiments were conducted within agricultural fields. Experiments were performed on the midslope (eroding) and toeslope (depositional) sections of representative hillslopes, under a variety of land managements, including row crop (conventional and conservation) and restored grasslands. Sensors were utilized to capture the evolution of soil moisture, temperature, microbial respiration pulses, and discharge rates to identify pseudo-steady state conditions. Samples collected at the weir outlet were tested for sediment concentrations and size fractions, as well as carbon and lignin fluxes. Preliminary findings show that conservation management practices have higher aggregate stability and decreased mass fluxes of carbon in the downslope than conventional tillage techniques.

Exciton Level Structure and Dynamics in Tubular Porphyrin Aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Yan; Stradomska, Anna; Fong, Sarah

2014-10-30

We present an account of the optical properties of the Frenkel excitons in self-assembled porphyrin tubular aggregates that represent an analog to natural photosynthetic antennae. Using a combination of ultrafast optical spectroscopy and stochastic exciton modeling, we address both linear and nonlinear exciton absorption, relaxation pathways, and the role of disorder. The static disorder-dominated absorption and fluorescence line widths show little temperature dependence for the lowest excitons (Q band), which we successfully simulate using a model of exciton scattering on acoustic phonons in the host matrix. Temperature-dependent transient absorption of and fluorescence from the excitons in the tubular aggregates aremore » marked by nonexponential decays with time scales ranging from a few picoseconds to a few nanoseconds, reflecting complex relaxation mechanisms. Combined experimental and theoretical investigations indicate that nonradiative pathways induced by traps and defects dominate the relaxation of excitons in the tubular aggregates. We model the pumpprobe spectra and ascribe the excited-state absorption to transitions from one-exciton states to a manifold of mixed one- and two-exciton states. Our results demonstrate that while the delocalized Frenkel excitons (over 208 (1036) molecules for the optically dominant excitons in the Q (B) band) resulting from strong intermolecular coupling in these aggregates could potentially facilitate efficient energy transfer, fast relaxation due to defects and disorder probably present a major limitation for exciton transport over large distances.« less

Protein Aggregates Are Recruited to Aggresome by Histone Deacetylase 6 via Unanchored Ubiquitin C Termini*

PubMed Central

Ouyang, Hui; Ali, Yousuf O.; Ravichandran, Mani; Dong, Aiping; Qiu, Wei; MacKenzie, Farrell; Dhe-Paganon, Sirano; Arrowsmith, Cheryl H.; Zhai, R. Grace

2012-01-01

The aggresome pathway is activated when proteasomal clearance of misfolded proteins is hindered. Misfolded polyubiquitinated protein aggregates are recruited and transported to the aggresome via the microtubule network by a protein complex consisting of histone deacetylase 6 (HDAC6) and the dynein motor complex. The current model suggests that HDAC6 recognizes protein aggregates by binding directly to polyubiquitinated proteins. Here, we show that there are substantial amounts of unanchored ubiquitin in protein aggregates with solvent-accessible C termini. The ubiquitin-binding domain (ZnF-UBP) of HDAC6 binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin instead of conjugated polyubiquitin. The unanchored ubiquitin C termini in the aggregates are generated in situ by aggregate-associated deubiquitinase ataxin-3. These results provide structural and mechanistic bases for the role of HDAC6 in aggresome formation and further suggest a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C termini within protein aggregates enables HDAC6 recognition and transport to the aggresome. PMID:22069321

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagaoka, Masataka; Core Research for Evolutional Science and Technology; ESICB, Kyoto University, Kyodai Katsura, Nishikyo-ku, Kyoto 615-8520

A new efficient hybrid Monte Carlo (MC)/molecular dynamics (MD) reaction method with a rare event-driving mechanism is introduced as a practical ‘atomistic’ molecular simulation of large-scale chemically reactive systems. Starting its demonstrative application to the racemization reaction of (R)-2-chlorobutane in N,N-dimethylformamide solution, several other applications are shown from the practical viewpoint of molecular controlling of complex chemical reactions, stereochemistry and aggregate structures. Finally, I would like to mention the future applications of the hybrid MC/MD reaction method.

Enhanced removal of As (V) from aqueous solution using modified hydrous ferric oxide nanoparticles

PubMed Central

Huo, Lijuan; Zeng, Xibai; Su, Shiming; Bai, Lingyu; Wang, Yanan

2017-01-01

Hydrous ferric oxide (HFO) is most effective with high treatment capacity on arsenate [As(V)] sorption although its transformation and aggregation nature need further improvement. Here, HFO nanoparticles with carboxymethyl cellulose (CMC) or starch as modifier was synthesized for the purpose of stability improvement and As(V) removal from water. Comparatively, CMC might be the optimum stabilizer for HFO nanoparticles because of more effective physical and chemical stability. The large-pore structure, high surface specific area, and the non-aggregated nature of CMC-HFO lead to increased adsorption sites, and thus high adsorption capacities of As(V) without pre-treatment (355 mg·g−1), which is much greater than those reported in previous studies. Second-order equation and dual-mode isotherm model could be successfully used to interpret the sorption kinetics and isotherms of As(V), respectively. FTIR, XPS and XRD analyses suggested that precipitation and surface complexation were primary mechanisms for As(V) removal by CMC modified HFO nanoparticles. A surface complexation model (SCM) was used to simulate As adsorption over pH 2.5–10.4. The predominant adsorbed arsenate species were modeled as bidentate binuclear surface complexes at low pH and as monodentate complexes at high pH. The immobilized arsenic remained stable when aging for 270 d at room temperature. PMID:28098196

Enhanced removal of As (V) from aqueous solution using modified hydrous ferric oxide nanoparticles

NASA Astrophysics Data System (ADS)

Huo, Lijuan; Zeng, Xibai; Su, Shiming; Bai, Lingyu; Wang, Yanan

2017-01-01

Hydrous ferric oxide (HFO) is most effective with high treatment capacity on arsenate [As(V)] sorption although its transformation and aggregation nature need further improvement. Here, HFO nanoparticles with carboxymethyl cellulose (CMC) or starch as modifier was synthesized for the purpose of stability improvement and As(V) removal from water. Comparatively, CMC might be the optimum stabilizer for HFO nanoparticles because of more effective physical and chemical stability. The large-pore structure, high surface specific area, and the non-aggregated nature of CMC-HFO lead to increased adsorption sites, and thus high adsorption capacities of As(V) without pre-treatment (355 mg·g-1), which is much greater than those reported in previous studies. Second-order equation and dual-mode isotherm model could be successfully used to interpret the sorption kinetics and isotherms of As(V), respectively. FTIR, XPS and XRD analyses suggested that precipitation and surface complexation were primary mechanisms for As(V) removal by CMC modified HFO nanoparticles. A surface complexation model (SCM) was used to simulate As adsorption over pH 2.5-10.4. The predominant adsorbed arsenate species were modeled as bidentate binuclear surface complexes at low pH and as monodentate complexes at high pH. The immobilized arsenic remained stable when aging for 270 d at room temperature.

Environmental Stress-mediated EPS Production Shape Microbial Activity on Various Hydrated Rough Surfaces

NASA Astrophysics Data System (ADS)

Wang, G.; Liu, L.; Chen, G.

2016-12-01

The complex environmental physical and chemical processes and interplay with the associating biological responses are keys to understanding the environmental microbiology ensconced in environmental remediation, water quality control, food safety, nutrient cycling, and etc., yet remain poorly understood. Using experimental micromodels, we study how environmental conditions (e.g., hydration fluctuation, nutrient limitation, pH variation, etc.) affect microbial extracellular polymeric substances (EPS) production and their configuration within various hydrated surfaces, and impacts on microbial motility, surface attachment, aggregation, and other bioremediation activities. To elucidate the potential mechanisms underlying the complex bio-physicochemical processes, we developed an individual-based and spatio-temporally resolved modeling platform that explicitly considers microscale aqueous-phase configuration and nutrient transport/diffusion and associated biophysical processes affecting individual microbial cell life history. We quantitatively explore the effects of the above microscale environmental processes on bio-physicochemical interactions affecting microbial growth, motility, surface attachment and aggregation, and shaping population interactions and functions. Simulation scenarios of microbial induced pollutant (e.g., roxarsone) biotransformation on various hydrated rough surfaces will also be present.

Cu(II) potentiation of Alzheimer Abeta1-40 cytotoxicity and transition on its secondary structure.

PubMed

Dai, Xue-Ling; Sun, Ya-Xuan; Jiang, Zhao-Feng

2006-11-01

Mounting evidence has shown that dyshomeostasis of the redox-active biometals such as Cu and Fe can lead to oxidative stress, which plays a key role in the neuropathology of Alzheimer' disease (AD). Here we demonstrate that with the formation of Cu(II).beta1-40 complexes, copper markedly potentiates the neurotoxicity exhibited by beta-amyloid peptide (Ab). A greater amount of hydrogen peroxide was released when Cu(II).beta1-40 complexes was added to the xanthine oxidase/xanthine system detected by potassium iodide spectrophotometry. Copper bound to Abeta1-40 was observed by electron paramagnetic resonance (EPR) spectroscopy. Circular dichroism (CD) studies indicated that copper chelation could cause a structural transition of Abeta. The addition of copper to Ab introduced an increase on beta-sheet as well as alpha-helix, which may be responsible for the aggregation of Abeta. We hypothesized that Abeta aggregation induced by copper may be responsible for local injury in AD. The interaction between Cu(2+) and Ab also provides a possible mechanism for the enrichment of metal ions in amyloid plaques in the AD brain.

Binding Modes of Phthalocyanines to Amyloid β Peptide and Their Effects on Amyloid Fibril Formation.

PubMed

Valiente-Gabioud, Ariel A; Riedel, Dietmar; Outeiro, Tiago F; Menacho-Márquez, Mauricio A; Griesinger, Christian; Fernández, Claudio O

2018-03-13

The inherent tendency of proteins to convert from their native states into amyloid aggregates is associated with a range of human disorders, including Alzheimer's and Parkinson's diseases. In that sense, the use of small molecules as probes for the structural and toxic mechanism related to amyloid aggregation has become an active area of research. Compared with other compounds, the structural and molecular basis behind the inhibitory interaction of phthalocyanine tetrasulfonate (PcTS) with proteins such as αS and tau has been well established, contributing to a better understanding of the amyloid aggregation process in these proteins. We present here the structural characterization of the binding of PcTS and its Cu(II) and Zn(II)-loaded forms to the amyloid β-peptide (Aβ) and the impact of these interactions on the peptide amyloid fibril assembly. Elucidation of the PcTS binding modes to Aβ 40 revealed the involvement of specific aromatic and hydrophobic interactions in the formation of the Aβ 40 -PcTS complex, ascribed to a binding mode in which the planarity and hydrophobicity of the aromatic ring system in the phthalocyanine act as main structural determinants for the interaction. Our results demonstrated that formation of the Aβ 40 -PcTS complex does not interfere with the progression of the peptide toward the formation of amyloid fibrils. On the other hand, conjugation of Zn(II) but not Cu(II) at the center of the PcTS macrocyclic ring modified substantially the binding profile of this phthalocyanine to Aβ 40 and became crucial to reverse the effects of metal-free PcTS on the fibril assembly of the peptide. Overall, our results provide a firm basis to understand the structural rules directing phthalocyanine-protein interactions and their implications on the amyloid fibril assembly of the target proteins; in particular, our results contradict the hypothesis that PcTS might have similar mechanisms of action in slowing the formation of a variety of pathological aggregates. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Spatial complexity reduces interaction strengths in the meta-food web of a river floodplain mosaic

USGS Publications Warehouse

Bellmore, James Ryan; Baxter, Colden Vance; Connolly, Patrick J.

2015-01-01

Theory states that both the spatial complexity of landscapes and the strength of interactions between consumers and their resources are important for maintaining biodiversity and the 'balance of nature.' Spatial complexity is hypothesized to promote biodiversity by reducing potential for competitive exclusion; whereas, models show weak trophic interactions can enhance stability and maintain biodiversity by dampening destabilizing oscillations associated with strong interactions. Here we show that spatial complexity can reduce the strength of consumer-resource interactions in natural food webs. By sequentially aggregating food webs of individual aquatic habitat patches across a floodplain mosaic, we found that increasing spatial complexity resulted in decreases in the strength of interactions between predators and prey, owing to a greater proportion of weak interactions and a reduced proportion of strong interactions in the meta-food web. The main mechanism behind this pattern was that some patches provided predation refugia for species which were often strongly preyed upon in other patches. If weak trophic interactions do indeed promote stability, then our findings may signal an additional mechanism by which complexity and stability are linked in nature. In turn, this may have implications for how the values of landscape complexity, and the costs of biophysical homogenization, are assessed.

Uncovering the mechanism of aggregation of human transthyretin

DOE PAGES

Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.; ...

2015-10-12

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability

NASA Astrophysics Data System (ADS)

Camilloni, Carlo; Sala, Benedetta Maria; Sormanni, Pietro; Porcari, Riccardo; Corazza, Alessandra; De Rosa, Matteo; Zanini, Stefano; Barbiroli, Alberto; Esposito, Gennaro; Bolognesi, Martino; Bellotti, Vittorio; Vendruscolo, Michele; Ricagno, Stefano

2016-05-01

A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.

On Decision-Making Among Multiple Rule-Bases in Fuzzy Control Systems

NASA Technical Reports Server (NTRS)

Tunstel, Edward; Jamshidi, Mo

1997-01-01

Intelligent control of complex multi-variable systems can be a challenge for single fuzzy rule-based controllers. This class of problems cam often be managed with less difficulty by distributing intelligent decision-making amongst a collection of rule-bases. Such an approach requires that a mechanism be chosen to ensure goal-oriented interaction between the multiple rule-bases. In this paper, a hierarchical rule-based approach is described. Decision-making mechanisms based on generalized concepts from single-rule-based fuzzy control are described. Finally, the effects of different aggregation operators on multi-rule-base decision-making are examined in a navigation control problem for mobile robots.

Nature-Inspired Strategy toward Superhydrophobic Fabrics for Versatile Oil/Water Separation.

PubMed

Zhou, Cailong; Chen, Zhaodan; Yang, Hao; Hou, Kun; Zeng, Xinjuan; Zheng, Yanfen; Cheng, Jiang

2017-03-15

Phytic acid, which is a naturally occurring component that is widely found in many plants, can strongly bond toxic mineral elements in the human body, because of its six phosphate groups. Some of the metal ions present the property of bonding with phytic acid to form insoluble coordination complexes aggregations, even at room temperature. Herein, a superhydrophobic cotton fabric was prepared using a novel and facile nature-inspired strategy that introduced phytic acid metal complex aggregations to generate rough hierarchical structures on a fabric surface, followed by PDMS modification. This superhydrophobic surface can be constructed not only on cotton fabric, but also on filter paper, polyethylene terephthalate (PET) fabric, and sponge. Ag I , Fe III , Ce III , Zr IV , and Sn IV are very commendatory ions in our study. Taking phytic acid-Fe III -based superhydrophobic fabric as an example, it showed excellent resistance to ultraviolet (UV) irradiation, high temperature, and organic solvent immersion, and it has good resistance to mechanical wear and abrasion. The superhydrophobic/superoleophilic fabric was successfully used to separate oil/water mixtures with separation efficiencies as high as 99.5%. We envision that these superantiwetting fabrics, modified with phytic acid-metal complexes and PDMS, are environmentally friendly, low cost, sustainable, and easy to scale up, and thereby exhibit great potentials in practical applications.

Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade.

PubMed

Chiti, Fabrizio; Dobson, Christopher M

2017-06-20

Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidoses. In this review, we describe this field of science with particular reference to the advances that have been made over the last decade in our understanding of its fundamental nature and consequences. We list the proteins that are known to be deposited as amyloid or other types of aggregates in human tissues and the disorders with which they are associated, as well as the proteins that exploit the amyloid motif to play specific functional roles in humans. In addition, we summarize the genetic factors that have provided insight into the mechanisms of disease onset. We describe recent advances in our knowledge of the structures of amyloid fibrils and their oligomeric precursors and of the mechanisms by which they are formed and proliferate to generate cellular dysfunction. We show evidence that a complex proteostasis network actively combats protein aggregation and that such an efficient system can fail in some circumstances and give rise to disease. Finally, we anticipate the development of novel therapeutic strategies with which to prevent or treat these highly debilitating and currently incurable conditions.

Plasma based formation and deposition of metal and metal oxide nanoparticles using a gas aggregation source

NASA Astrophysics Data System (ADS)

Polonskyi, Oleksandr; Ahadi, Amir Mohammad; Peter, Tilo; Fujioka, Kenji; Abraham, Jan Willem; Vasiliauskaite, Egle; Hinz, Alexander; Strunskus, Thomas; Wolf, Sebastian; Bonitz, Michael; Kersten, Holger; Faupel, Franz

2018-05-01

Metal clusters and nanoparticles (NPs) have been studied intensively due to their unique chemical, physical, electrical, and optical properties, resulting from their dimensions, which provided host of applications in nanoscience and nanotechnology. Formation of new materials by embedding NPs into various matrices (i.e. formation of nanocomposites) further expands the horizon of possible application of such nanomaterials. In the last few decades, the focus was put on the formation of metallic and metal oxide NPs via a so-called gas aggregation nanoparticle source employing magnetron sputtering (i.e. Haberland concept). In this paper, an overview is given of the recent progress in formation and deposition of NPs by the gas aggregation method. Examples range from noble metals (Ag, Au) through reactive metals (Al, Ti) to Si and the respective oxides. Emphasis is placed on the mechanism of nanoparticle growth and the resulting properties. Moreover, kinetic Monte Carlo simulations were developed to explain the growth mechanism and dynamics of nanoparticle formation depending on the experimental conditions. In addition, the role of trace amounts of reactive gases and of pulsed operation of the plasma on the nucleation process is addressed. Finally, the treatment of the NPs in the plasma environment resulting in nanoparticle charging, morphological and chemical modifications is discussed. Contribution to the Topical Issue "Fundamentals of Complex Plasmas", edited by Jürgen Meichsner, Michael Bonitz, Holger Fehske, Alexander Piel.

Physical principles of filamentous protein self-assembly kinetics

NASA Astrophysics Data System (ADS)

Michaels, Thomas C. T.; Liu, Lucie X.; Meisl, Georg; Knowles, Tuomas P. J.

2017-04-01

The polymerization of proteins and peptides into filamentous supramolecular structures is an elementary form of self-organization of key importance to the functioning biological systems, as in the case of actin biofilaments that compose the cellular cytoskeleton. Aberrant filamentous protein self-assembly, however, is associated with undesired effects and severe clinical disorders, such as Alzheimer’s and Parkinson’s diseases, which, at the molecular level, are associated with the formation of certain forms of filamentous protein aggregates known as amyloids. Moreover, due to their unique physicochemical properties, protein filaments are finding extensive applications as biomaterials for nanotechnology. With all these different factors at play, the field of filamentous protein self-assembly has experienced tremendous activity in recent years. A key question in this area has been to elucidate the microscopic mechanisms through which filamentous aggregates emerge from dispersed proteins with the goal of uncovering the underlying physical principles. With the latest developments in the mathematical modeling of protein aggregation kinetics as well as the improvement of the available experimental techniques it is now possible to tackle many of these complex systems and carry out detailed analyses of the underlying microscopic steps involved in protein filament formation. In this paper, we review some classical and modern kinetic theories of protein filament formation, highlighting their use as a general strategy for quantifying the molecular-level mechanisms and transition states involved in these processes.

Hollow-fiber flow field-flow fractionation with multi-angle laser scattering detection for aggregation studies of therapeutic proteins.

PubMed

Reschiglian, P; Roda, B; Zattoni, A; Tanase, M; Marassi, V; Serani, S

2014-02-01

The rapid development of protein-based pharmaceuticals highlights the need for robust analytical methods to ensure their quality and stability. Among proteins used in pharmaceutical applications, an important and ever increasing role is represented by monoclonal antibodies and large proteins, which are often modified to enhance their activity or stability when used as drugs. The bioactivity and the stability of those proteins are closely related to the maintenance of their complex structure, which however are influenced by many external factors that can cause degradation and/or aggregation. The presence of aggregates in these drugs could reduce their bioactivity and bioavailability, and induce immunogenicity. The choice of the proper analytical method for the analysis of aggregates is fundamental to understand their (size) dimensional range, their amount, and if they are present in the sample as generated by an aggregation or as an artifact due to the method itself. Size exclusion chromatography is one of the most important techniques for the quality control of pharmaceutical proteins; however, its application is limited to relatively low molar mass aggregates. Among the techniques for the size characterization of proteins, field-flow fractionation (FFF) represents a competitive choice because of its soft mechanism due to the absence of a stationary phase and application in a broader size range, from nanometer- to micrometer-sized analytes. In this paper, the microcolumn variant of FFF, the hollow-fiber flow FFF, was online coupled with multi-angle light scattering, and a method for the characterization of aggregates with high reproducibility and low limit of detection was demonstrated employing an avidin derivate as sample model.

Regulator LdhR and d-Lactate Dehydrogenase LdhA of Burkholderia multivorans Play Roles in Carbon Overflow and in Planktonic Cellular Aggregate Formation.

PubMed

Silva, Inês N; Ramires, Marcelo J; Azevedo, Lisa A; Guerreiro, Ana R; Tavares, Andreia C; Becker, Jörg D; Moreira, Leonilde M

2017-10-01

LysR-type transcriptional regulators (LTTRs) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several types of bacteria, few have been characterized in Burkholderia Here, we show that gene ldhR of B. multivorans encoding an LTTR is cotranscribed with ldhA encoding a d-lactate dehydrogenase and evaluate their implication in virulence traits such as exopolysaccharide (EPS) synthesis and biofilm formation. A comparison of the wild type (WT) and its isogenic Δ ldhR mutant grown in medium with 2% d-glucose revealed a negative impact on EPS biosynthesis and on cell viability in the presence of LdhR. The loss of viability in WT cells was caused by intracellular acidification as a consequence of the cumulative secretion of organic acids, including d-lactate, which was absent from the Δ ldhR mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1,000 μm in size after 24 h in liquid cultures, in contrast to Δ ldhR mutant aggregates that never grew more than 60 μm. The overexpression of d-lactate dehydrogenase LdhA in the Δ ldhR mutant partially restored the formed aggregate size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in Burkholderia CF clinical isolates showed aggregates in 40 of 74. As CF patients' lung environments are microaerophilic and bacteria are found as free aggregates/biofilms, LdhR and LdhA might have central roles in adapting to this environment. IMPORTANCE Cystic fibrosis patients often suffer from chronic respiratory infections caused by several types of microorganisms. Among them are the Burkholderia cepacia complex bacteria, which cause progressive deterioration of lung function that, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as "cepacia syndrome." Burkholderia pathogenesis is multifactorial as they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As Burkholderia is commonly found in CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study, we demonstrate the importance of a d-lactate dehydrogenase and a regulator in regulating carbon overflow, cellular aggregates, and surface-attached biofilm formation. This not only enhances our understanding of Burkholderia pathogenesis but can also lead to the development of drugs against these proteins to circumvent biofilm formation. Copyright © 2017 American Society for Microbiology.

Self-organization of intertidal snails facilitates evolution of aggregation behavior.

PubMed

Stafford, Richard; Davies, Mark S; Williams, Gray A

2008-01-01

Many intertidal snails form aggregations during emersion to minimize desiccation stress. Here we investigate possible mechanisms for the evolution of such behavior. Two behavioral traits (following of mucus trails, and crevice occupation), which both provide selective advantages to individuals that possess the traits over individuals that do not, result in self-organization of aggregations in crevices in the rock surface. We suggest that the existence of self-organizing aggregations provides a mechanism by which aggregation behavior can evolve. The inclusion of an explicitly coded third behavior, aggregation, in a simulated population produces patterns statistically similar to those found on real rocky shores. Allowing these three behaviors to evolve using an evolutionary algorithm, however, results in aggregation behavior being selected against on shores with high crevice density. The inclusion of broadcast spawning dispersal mechanisms in the simulation, however, results in aggregation behavior evolving as predicted on shores with both high crevice density and low crevice density (evolving in crevices first, and then both in crevices and on flat rock), indicating the importance of environmental interactions in understanding evolutionary processes. We propose that self-organization can be an important factor in the evolution of group behaviors.

Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's disease treatment?

PubMed

Lin, Fang; Qin, Zheng-Hong

2013-01-01

Autophagy is a degradation pathway for long-lived cytoplasmic proteins, protein complexes, or damaged organelles. The accumulation and aggregation of misfolded proteins are hallmarks of several neurodegenerative diseases. Many researchers have reported that autophagy degrades disease-causing misfolded and aggregated proteins, including mutant huntingtin (Htt) in Huntington's disease, mutant synuclein in familial Parkingson's disease, mutant Cu, Zn-Superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis. In this review, we will bring up new evidence to elucidate the involvement of autophagy in degradation of mutant Htt, discuss the mechanisms regulating the degradation of mutant Htt by autophagy and the therapeutic effects of drugs that enhance autophagy to improve clearance of mutant Htt. We propose that enhancement of autophagy by drugs may be a strategy to treat or retard progression of Huntington's disease.

Low-Dimensional Oxygen Vacancy Ordering and Diffusion in SrCrO 3$-$δ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ong, Phuong-Vu; Du, Yingge; Sushko, Peter V.

2017-04-06

We investigate the formation mechanisms of vacancy-ordered phase and collective mass transport in epitaxial SrCrO 3$-$δ films using ab initio simulations within the density functional theory formalism. We show that as concentration of oxygen vacancies (V O’s) increases, they form one-dimensional (1D) chains that feature Cr-centered tetrahedra. Aggregation of these 1D V O-chains results in the formation of (111)-oriented oxygen-deficient planes (V O-planes) and an extended vacancy-ordered phase observed in recent experiments. We discuss atomic scale mechanisms enabling the quasi-2D V O aggregates to expand along and translate across (111) planes. The corresponding lowest activation energy pathways necessarily involve rotationmore » of Cr-centered tetrahedra, which emerges as a universal feature of fast ionic conduction in complex oxides. These findings explain reversible oxidation and reduction in SrCrO 3$-$δ at low-temperatures and provide insights into transient behavior necessary to harness ionic conductive oxides for high performance and low-temperature electrochemical reactors.« less

CARS microscopy of Alzheimer's diseased brain tissue

NASA Astrophysics Data System (ADS)

Enejder, Annika; Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia-Yi

2014-02-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.

Integrating a piezoelectric actuator with mechanical and hydraulic devices to control camless engines

NASA Astrophysics Data System (ADS)

Mercorelli, Paolo; Werner, Nils

2016-10-01

The paper deals with some interdisciplinary aspects and problems concerning the actuation control which occur in the integration of a piezoelectric structure in an aggregate actuator consisting of a piezoelectric, a stroke ratio displacement, a mechanical and a hydraulic part. Problems like compensation of the piezo hysteresis effect, scaling force-position to obtain an adequate displacement of the actuator and finally the control of such a complex aggregate system are considered and solved. Even though this work considers a particular application, the solutions proposed in the paper are quite general. In fact, the considered technical aspects occurring in systems which utilize piezoelectric technologies can be used in a variegated gamma of actuators integrating piezoelectric technologies. A cascade controller is proposed to combine a Feedforward action with an internal and an external PI-Controller. The Feedforward Controller is based on the model of the whole actuator, so particular attention is paid to the model structure. The resulting Feedforward action is an adaptive one to compensate hydraulic pressure faults. Real measurements are shown.

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

PubMed Central

Liu, Siqi; Xu, Yi-Jun

2016-01-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters–TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability. PMID:26947754

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

NASA Astrophysics Data System (ADS)

Liu, Siqi; Xu, Yi-Jun

2016-03-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters-TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability.

Amyloid and membrane complexity: The toxic interplay revealed by AFM.

PubMed

Canale, Claudio; Oropesa-Nuñez, Reinier; Diaspro, Alberto; Dante, Silvia

2018-01-01

Lipid membranes play a fundamental role in the pathological development of protein misfolding diseases. Several pieces of evidence suggest that the lipid membrane could act as a catalytic surface for protein aggregation. Furthermore, a leading theory indicates the interaction between the cell membrane and misfolded oligomer species as the responsible for cytotoxicity, hence, for neurodegeneration in disorders such as Alzheimer's and Parkinson's disease. The definition of the mechanisms that drive the interaction between pathological protein aggregates and plasma membrane is fundamental for the development of effective therapies for a large class of diseases. Atomic force microscopy (AFM) has been employed to study how amyloid aggregates affect the cell physiological properties. Considerable efforts were spent to characterize the interaction with model systems, i.e., planar supported lipid bilayers, but some works also addressed the problem directly on living cells. Here, an overview of the main works involving the use of the AFM on both model system and living cells will be provided. Different kind of approaches will be presented, as well as the main results derived from the AFM analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells

PubMed Central

Burkhardt, Matthew F; Martinez, Fernando J; Wright, Sarah; Ramos, Carla; Volfson, Dmitri; Mason, Michael; Garnes, Jeff; Dang, Vu; Lievers, Jeffery; Shoukat-Mumtaz, Uzma; Martinez, Rita; Gai, Hui; Blake, Robert; Vaisberg, Eugeni; Grskovic, Marica; Johnson, Charles; Irion, Stefan; Bright, Jessica; Cooper, Bonnie; Nguyen, Leane; Griswold-Prenner, Irene; Javaherian, Ashkan

2016-01-01

Development of therapeutics for genetically complex neurodegenerative diseases such as sporadic amyotrophic lateral sclerosis (ALS) has largely been hampered by lack of relevant disease models. Reprogramming of sporadic ALS patients’ fibroblasts into induced pluripotent stem cells (iPSC) and differentiation into affected neurons that show a disease phenotype could provide a cellular model for disease mechanism studies and drug discovery. Here we report the reprogramming to pluripotency of fibroblasts from a large cohort of healthy controls and ALS patients and their differentiation into motor neurons. We demonstrate that motor neurons derived from three sALS patients show de novo TDP-43 aggregation and that the aggregates recapitulate pathology in postmortem tissue from one of the same patients from which the iPSC were derived. We configured a high-content chemical screen using the TDP-43 aggregate endpoint both in lower motor neurons and upper motor neuron like cells and identified FDA-approved small molecule modulators including Digoxin demonstrating the feasibility of patient-derived iPSC-based disease modelling for drug screening. PMID:23891805

Cryptic Amyloidogenic Elements in the 3′ UTRs of Neurofilament Genes Trigger Axonal Neuropathy

PubMed Central

Rebelo, Adriana P.; Abrams, Alexander J.; Cottenie, Ellen; Horga, Alejandro; Gonzalez, Michael; Bis, Dana M.; Sanchez-Mejias, Avencia; Pinto, Milena; Buglo, Elena; Markel, Kasey; Prince, Jeffrey; Laura, Matilde; Houlden, Henry; Blake, Julian; Woodward, Cathy; Sweeney, Mary G.; Holton, Janice L.; Hanna, Michael; Dallman, Julia E.; Auer-Grumbach, Michaela; Reilly, Mary M.; Zuchner, Stephan

2016-01-01

Abnormal protein aggregation is observed in an expanding number of neurodegenerative diseases. Here, we describe a mechanism for intracellular toxic protein aggregation induced by an unusual mutation event in families affected by axonal neuropathy. These families carry distinct frameshift variants in NEFH (neurofilament heavy), leading to a loss of the terminating codon and translation of the 3′ UTR into an extra 40 amino acids. In silico aggregation prediction suggested the terminal 20 residues of the altered NEFH to be amyloidogenic, which we confirmed experimentally by serial deletion analysis. The presence of this amyloidogenic motif fused to NEFH caused prominent and toxic protein aggregates in transfected cells and disrupted motor neurons in zebrafish. We identified a similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS (fused in sarcoma), in which mutations are known to cause aggregation in Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis, respectively. In summary, we present a protein-aggregation-triggering mechanism that should be taken into consideration during the evaluation of stop-loss variants. PMID:27040688

Chaperone-assisted protein aggregate reactivation: Different solutions for the same problem.

PubMed

Aguado, Alejandra; Fernández-Higuero, José Angel; Moro, Fernando; Muga, Arturo

2015-08-15

The oligomeric AAA+ chaperones Hsp104 in yeast and ClpB in bacteria are responsible for the reactivation of aggregated proteins, an activity essential for cell survival during severe stress. The protein disaggregase activity of these members of the Hsp100 family is linked to the activity of chaperones from the Hsp70 and Hsp40 families. The precise mechanism by which these proteins untangle protein aggregates remains unclear. Strikingly, Hsp100 proteins are not present in metazoans. This does not mean that animal cells do not have a disaggregase activity, but that this activity is performed by the Hsp70 system and a representative of the Hsp110 family instead of a Hsp100 protein. This review describes the actual view of Hsp100-mediated aggregate reactivation, including the ATP-induced conformational changes associated with their disaggregase activity, the dynamics of the oligomeric assembly that is regulated by its ATPase cycle and the DnaK system, and the tight allosteric coupling between the ATPase domains within the hexameric ring complexes. The lack of homologs of these disaggregases in metazoans has suggested that they might be used as potential targets to develop antimicrobials. The current knowledge of the human disaggregase machinery and the role of Hsp110 are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Lithiated imines: solvent-dependent aggregate structures and mechanisms of alkylation.

PubMed

Zuend, Stephan J; Ramirez, Antonio; Lobkovsky, Emil; Collum, David B

2006-05-03

We describe efforts to understand the structure and reactivity of lithiated cyclohexanone N-cyclohexylimine. The lithioimine affords complex solvent-dependent distributions of monomers, dimers, and trimers in a number of ethereal solvents. Careful selection of solvent provides exclusively monosolvated dimers. Rate studies on the C-alkylations reveal chronic mixtures of monomer- and dimer-based pathways. We explore the factors influencing reactants and alkylation transition structures and the marked differences between lithioimines and isostructural lithium dialkylamides with the aid of density functional theory calculations.

Residual Mechanical Properties of Concrete Made with Crushed Clay Bricks and Roof Tiles Aggregate after Exposure to High Temperatures

PubMed Central

Miličević, Ivana; Štirmer, Nina; Banjad Pečur, Ivana

2016-01-01

This paper presents the residual mechanical properties of concrete made with crushed bricks and clay roof tile aggregates after exposure to high temperatures. One referent mixture and eight mixtures with different percentages of replacement of natural aggregate by crushed bricks and roof tiles are experimentally tested. The properties of the concrete were measured before and after exposure to 200, 400, 600 and 800 °C. In order to evaluate the basic residual mechanical properties of concrete with crushed bricks and roof tiles after exposure to high temperatures, ultrasonic pulse velocity is used as a non-destructive test method and the results are compared with those of a destructive method for validation. The mixture with the highest percentage of replacement of natural aggregate by crushed brick and roof tile aggregate has the best physical, mechanical, and thermal properties for application of such concrete in precast concrete elements exposed to high temperatures. PMID:28773420

Protein Aggregates Are Recruited to Aggresome by Histone Deacetylase 6 via Unanchored Ubiquitin C Termini

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Hui; Ali, Yousuf O.; Ravichandran, Mani

2012-07-11

The aggresome pathway is activated when proteasomal clearance of misfolded proteins is hindered. Misfolded polyubiquitinated protein aggregates are recruited and transported to the aggresome via the microtubule network by a protein complex consisting of histone deacetylase 6 (HDAC6) and the dynein motor complex. The current model suggests that HDAC6 recognizes protein aggregates by binding directly to polyubiquitinated proteins. Here, we show that there are substantial amounts of unanchored ubiquitin in protein aggregates with solvent-accessible C termini. The ubiquitin-binding domain (ZnF-UBP) of HDAC6 binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin instead of conjugated polyubiquitin. The unanchored ubiquitin Cmore » termini in the aggregates are generated in situ by aggregate-associated deubiquitinase ataxin-3. These results provide structural and mechanistic bases for the role of HDAC6 in aggresome formation and further suggest a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C termini within protein aggregates enables HDAC6 recognition and transport to the aggresome.« less

Assessment of the ``cross-bridge''-induced interaction of red blood cells by optical trapping combined with microfluidics

NASA Astrophysics Data System (ADS)

Lee, Kisung; Wagner, Christian; Priezzhev, Alexander V.

2017-09-01

Red blood cell (RBC) aggregation is an intrinsic property of the blood that has a direct effect on the blood viscosity and circulation. Nevertheless, the mechanism behind the RBC aggregation has not been confirmed and is still under investigation with two major hypotheses, known as "depletion layer" and "cross-bridging." We aim to ultimately understand the mechanism of the RBC aggregation and clarify both models. To measure the cell interaction in vitro in different suspensions (including plasma, isotonic solution of fibrinogen, isotonic solution of fibrinogen with albumin, and phosphate buffer saline) while moving the aggregate from one solution to another, an approach combining optical trapping and microfluidics has been applied. The study reveals evidence that RBC aggregation in plasma is at least partly due to the cross-bridging mechanism. The cell interaction strength measured in the final solution was found to be significantly changed depending on the initial solution where the aggregate was formed.

Microfluidic model experiments on the injectability of monoclonal antibody solutions

NASA Astrophysics Data System (ADS)

Duchene, Charles; Filipe, Vasco; Nakach, Mostafa; Huille, Sylvain; Lindner, Anke

2017-11-01

Autoinjection devices that allow patients to self-administer medicine are becoming used more frequently; however, this advance comes with an increased need for precision in the injection process. The rare occurrence of protein aggregates in solutions of monoclonal antibodies constitutes a threat to the reliability of such devices. Here we study the flow of protein solutions containing aggregates in microfluidic model systems, mimicking injection devices, to gain fundamental understanding of the catastrophic clogging of constrictions of given size. We form aggregates by mechanically shaking or heating antibody solutions and then inject these solutions into microfluidic channels with varying types of constrictions. Geometrical clogging occurs when aggregates reach the size of the constriction and can in some cases be undone by increasing the applied pressure. We perform systematic experiments varying the relative aggregate size and the flow rate or applied pressure. The mechanical deformation of aggregates during their passage through constrictions is investigated to gain a better understanding of the clogging and unclogging mechanisms.

Biological framework for soil aggregation: Implications for ecological functions.

NASA Astrophysics Data System (ADS)

Ghezzehei, Teamrat; Or, Dani

2016-04-01

Soil aggregation is heuristically understood as agglomeration of primary particles bound together by biotic and abiotic cementing agents. The organization of aggregates is believed to be hierarchical in nature; whereby primary particles bond together to form secondary particles and subsequently merge to form larger aggregates. Soil aggregates are not permanent structures, they continuously change in response to internal and external forces and other drivers, including moisture, capillary pressure, temperature, biological activity, and human disturbances. Soil aggregation processes and the resulting functionality span multiple spatial and temporal scales. The intertwined biological and physical nature of soil aggregation, and the time scales involved precluded a universally applicable and quantifiable framework for characterizing the nature and function of soil aggregation. We introduce a biophysical framework of soil aggregation that considers the various modes and factors of the genesis, maturation and degradation of soil aggregates including wetting/drying cycles, soil mechanical processes, biological activity and the nature of primary soil particles. The framework attempts to disentangle mechanical (compaction and soil fragmentation) from in-situ biophysical aggregation and provides a consistent description of aggregate size, hierarchical organization, and life time. It also enables quantitative description of biotic and abiotic functions of soil aggregates including diffusion and storage of mass and energy as well as role of aggregates as hot spots of nutrient accumulation, biodiversity, and biogeochemical cycles.

Mechanical Properties of Steel Fiber Reinforced all Lightweight Aggregate Concrete

NASA Astrophysics Data System (ADS)

Yang, Y. M.; Li, J. Y.; Zhen, Y.; Nie, Y. N.; Dong, W. L.

2018-05-01

In order to study the basic mechanical properties and failure characteristics of all lightweight aggregate concrete with different volume of steel fiber (0%, 1%, 2%), shale ceramsite is used as light coarse aggregate. The shale sand is made of light fine aggregate and mixed with different volume of steel fiber, and the mix proportion design of all lightweight aggregate concrete is carried out. The cubic compressive strength, axial compressive strength, flexural strength, splitting strength and modulus of elasticity of steel fiber all lightweight aggregate concrete were studied. Test results show that the incorporation of steel fiber can restrict the cracking of concrete, improve crack resistance; at the same time, it shows good plastic deformation ability and failure morphology. It lays a theoretical foundation for further research on the application of all lightweight aggregate concrete in structural systems.

Gold nanoparticles as a factor of influence on doxorubicin-bovine serum albumin complex

NASA Astrophysics Data System (ADS)

Goncharenko, N. A.; Pavlenko, O. L.; Dmytrenko, O. P.; Kulish, M. P.; Lopatynskyi, A. M.; Chegel, V. I.

2018-04-01

The interaction between doxorubicin (Dox) and bovine serum albumin (BSA) complex with gold nanoparticles (AuNPs) was investigated by optical spectroscopy. The optical absorption of Dox and BSA solutions was studied. The formation of Dox-BSA complexes with a binding constant K = 7.56 × 106 M-2 and the number of binding sites n = 2 was found out. With pH 6.9, the concentration of complexes is an order of magnitude lower than the concentration of unbound antibiotic molecules. Optical absorption in solutions of Dox-BSA conjugates in the presence of AuNPs undergoes a significant rearrangement, which manifests the changes in the magnitude of the hydrophobic interaction of BSA with Dox, changes in the conformational state of antibiotic, and, as a consequence, a plasmon-induced change in the mechanism of complex formation. The aggregation of the Dox-AuNPs conjugate depends on the presence and concentration of BSA and in the case of formation of the Dox-BSA complex is minimal.

Fractal Aggregates in Tennis Ball Systems

ERIC Educational Resources Information Center

Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

2009-01-01

We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

Nanoimaging to Prevent and Treat Alzheimer’s and Parkinson’s Diseases. Scientific/Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuri L. Lyubchenko, PhD, DSc

2012-12-20

This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimer’s, Parkinson’s and Huntington’s diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimer’s and Parkinson’s diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establishmore » an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.« less

Demography and movement patterns of leopard sharks (Triakis semifasciata) aggregating near the head of a submarine canyon along the open coast of southern California, USA

USGS Publications Warehouse

Nosal, D.C.; Cartamil, D.C.; Long, J.W.; Luhrmann, M.; Wegner, N.C.; Graham, J.B.

2013-01-01

The demography, spatial distribution, and movement patterns of leopard sharks (Triakis semifasciata) aggregating near the head of a submarine canyon in La Jolla, California, USA, were investigated to resolve the causal explanations for this and similar shark aggregations. All sharks sampled from the aggregation site (n=140) were sexually mature and 97.1 % were female. Aerial photographs taken during tethered balloon surveys revealed high densities of milling sharks of up to 5470 sharks ha-1. Eight sharks were each tagged with a continuous acoustic transmitter and manually tracked without interruption for up to 48 h. Sharks exhibited strong site-fidelity and were generally confined to a divergence (shadow) zone of low wave energy, which results from wave refraction over the steep bathymetric contours of the submarine canyon. Within this divergence zone, the movements of sharks were strongly localized over the seismically active Rose Canyon Fault. Tracked sharks spent most of their time in shallow water (≤2 m for 71.0 % and ≤10 m for 95.9 % of time), with some dispersing to deeper (max: 53.9 m) and cooler (min: 12.7 °C) water after sunset, subsequently returning by sunrise. These findings suggest multiple functions of this aggregation and that the mechanism controlling its formation, maintenance, and dissolution is complex and rooted in the sharks' variable response to numerous confounding environmental factors.

Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXβ2 Integrin-dependent Manner

PubMed Central

Pian, Yaya; Li, Xueqin; Zheng, Yuling; Wu, Xiaohong; Yuan, Yuan; Jiang, Yongqiang

2016-01-01

The Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283–721) binds to both the Aα and Bβ chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXβ2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia, and these data shed new light on the function of MRP in S. suis pathogenesis. PMID:27231021

Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXβ2 Integrin-dependent Manner.

PubMed

Pian, Yaya; Li, Xueqin; Zheng, Yuling; Wu, Xiaohong; Yuan, Yuan; Jiang, Yongqiang

2016-05-27

The Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283-721) binds to both the Aα and Bβ chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXβ2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia, and these data shed new light on the function of MRP in S. suis pathogenesis.

Classification and Characterization of Therapeutic Antibody Aggregates

PubMed Central

Joubert, Marisa K.; Luo, Quanzhou; Nashed-Samuel, Yasser; Wypych, Jette; Narhi, Linda O.

2011-01-01

A host of diverse stress techniques was applied to a monoclonal antibody (IgG2) to yield protein particles with varying attributes and morphologies. Aggregated solutions were evaluated for percent aggregation, particle counts, size distribution, morphology, changes in secondary and tertiary structure, surface hydrophobicity, metal content, and reversibility. Chemical modifications were also identified in a separate report (Luo, Q., Joubert, M. K., Stevenson, R., Narhi, L. O., and Wypych, J. (2011) J. Biol. Chem. 286, 25134–25144). Aggregates were categorized into seven discrete classes, based on the traits described. Several additional molecules (from the IgG1 and IgG2 subtypes as well as intravenous IgG) were stressed and found to be defined with the same classification system. The mechanism of protein aggregation and the type of aggregate formed depends on the nature of the stress applied. Different IgG molecules appear to aggregate by a similar mechanism under the same applied stress. Aggregates created by harsh mechanical stress showed the largest number of subvisible particles, and the class generated by thermal stress displayed the largest number of visible particles. Most classes showed a disruption of the higher order structure, with the degree of disorder depending on the stress process. Particles in all classes (except thermal stress) were at least partially reversible upon dilution in pH 5 buffer. High copper content was detected in isolated metal-catalyzed aggregates, a stress previously shown to produce immunogenic aggregates. In conclusion, protein aggregates can be a very heterogeneous population, whose qualities are the result of the type of stress that was experienced. PMID:21454532

Microstructural and fabric characterization of brittle-ductile transitional deformation of middle crustal rocks along the Jinzhou detachment fault zone, Northeast China

NASA Astrophysics Data System (ADS)

Zhang, Juyi; Jiang, Hao; Liu, Junlai

2017-04-01

Detachment fault zones (DFZs) of metamorphic core complexes generally root into the middle crust. Exhumed DFZs therefore generally demonstrate structural, microstructural and fabric features characteristic of middle to upper crustal deformation. The Jinzhou detachment fault zone from the Liaonan metamorphic core complex is characterized by the occurrence of a sequence of fault rocks due to progressive shearing along the fault zone during exhumation of the lower plate. From the exhumed fabric zonation, cataclastic rocks formed in the upper crust occur near the Jinzhou master detachment fault, and toward the lower plate gradually changed to mylonites, mylonitic gneisses and migmatitic gneisses. Correspondingly, these fault rocks have various structural, microstructural and fabric characteristics that were formed by different deformation and recrystallization mechanisms from middle to upper crustal levels. At the meanwhile, various structural styles for strain localization were formed in the DFZ. As strain localization occurs, rapid changes in deformation mechanisms are attributed to increases in strain rates or involvement of fluid phases during the brittle-ductile shearing. Optical microscopic studies reveal that deformed quartz aggregates in the lower part of the detachment fault zone are characterized by generation of dynamically recrystallized grains via SGR and BLG recrystallization. Quartz rocks from the upper part of the DFZ have quartz porphyroclasts in a matrix of very fine recrystallized grains. The porphyroclasts have mantles of sub-grains and margins grain boundary bulges. Electron backscattered diffraction technique (EBSD) quartz c-axis fabric analysis suggests that quartz grain aggregates from different parts of the DFZ possess distinct fabric complexities. The c-axis fabrics of deformed quartz aggregates from mylonitic rocks in the lower part of the detachment fault zone preserve Y-maxima which are ascribed to intermediate temperature deformation (500-630˚ C), whereas complicated fabric patterns (e.g. asymmetric single girdles) are formed in fault rocks from the upper part of the DFZ. The increasing fabric complexity is here interpreted as the result of progressive superposition of fault rocks by shearing either at relatively shallow levels or high rate of strain, during exhumation of the lower plate and shear zone rocks. The above observations and interpretations imply that dislocation creep processes contribute to the dynamic recrystallization of quartz in the middle crustal brittle-ductile transition. Progressive shearing as a consequence of exhumation of the lower plate of the MCC contributed to the obvious structural, microstructural and fabric superpositions. Strain localization occurs as the progressive shearing proceeded. Transition of mechanisms of deformation and dynamic recrystallization during strain localization may be resulted from changes in temperature conditions, in strain rates or addition of minor amount water.

Imaging of Cerebral Amyloid Angiopathy with Bivalent 99mTc-Hydroxamamide Complexes

NASA Astrophysics Data System (ADS)

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-01

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer’s disease (AD). We previously reported 99mTc-hydroxamamide (99mTc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for 99mTc-Ham complexes, and all 99mTc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent 99mTc-Ham complexes ([99mTc]SB2A and [99mTc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the 99mTc-Ham complex.

Imaging of Cerebral Amyloid Angiopathy with Bivalent (99m)Tc-Hydroxamamide Complexes.

PubMed

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-16

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported (99m)Tc-hydroxamamide ((99m)Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for (99m)Tc-Ham complexes, and all (99m)Tc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent (99m)Tc-Ham complexes ([(99m)Tc]SB2A and [(99m)Tc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the (99m)Tc-Ham complex.

In Situ Observations of Electric-Field Induced Nanoparticle Aggregation

NASA Astrophysics Data System (ADS)

Woehl, T. J.; Browning, N. D.; Ristenpart, W. D.

2010-11-01

Nanoparticles have been widely observed to aggregate laterally on electrodes in response to applied electric fields. The mechanism driving this behavior, however, is unclear. Several groups have interpreted the aggregation in terms of electrohydrodynamic or electroosmotic fluid motion, but little corroborating evidence has been presented. Notably, work to date has relied on post situ observations using electron microscopy. Here we present a fluorescence microscopy technique to track the dynamics of nanoparticle aggregation in situ. Fluorescent 20-nm polystyrene nanoparticles are observed to form optically visible aggregates in response to an applied AC field. Although single particle resolution is lost, the existence of aggregates on the electrode surface is marked by growing clusters of increasingly bright intensity. We present a systematic investigation of the effects of applied potential and frequency on the aggregation rate, and we interpret the behavior in terms of a mechanism based on electrically induced convective flow.

Topics in Probabilistic Judgment Aggregation

ERIC Educational Resources Information Center

Wang, Guanchun

2011-01-01

This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

Mechanical Properties of Lightweight Concrete Using Recycled Cement-Sand Brick as Coarse Aggregates Replacement

NASA Astrophysics Data System (ADS)

Joohari, Ilya; Farhani Ishak, Nor; Amin, Norliyati Mohd

2018-03-01

This paper presents the result of replacing natural course aggregate with recycled cement-sand brick (CSB) towards the mechanical properties of concrete. Natural aggregates were used in this study as a control sample to compare with recycled coarse aggregates. This study was also carried to determine the optimum proportion of coarse aggregates replacement to produce lightweight concrete. Besides, this study was conducted to observe the crack and its behaviour development during the mechanical testing. Through this study, four types of concrete mixed were prepared, which were the control sample, 25%, 50% and 75% replacement of CSB. The test conducted to determine the effectiveness of recycled CSB as coarse aggregates replacement in this study were slump test, density measurement, compression test, and flexural test and. The strength of concrete was tested at 7 days and 28 days of curing. From the results obtained, the optimum proportion which produced the highest strength is 25% replacement of recycled CSB. The compressive and flexural strength has decreased by 10%-12% and 4%-34% respectively compared to the control sample. The presence of recycled coarse aggregates in sample has decreased the density of concrete by 0.8%-3% compared to the control sample.

Hypothalamic ER–associated degradation regulates POMC maturation, feeding, and age-associated obesity

PubMed Central

Kim, Geun Hyang; Somlo, Diane R.M.; Haataja, Leena; Song, Soobin; Nillni, Eduardo A.

2018-01-01

Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism. Here, we report a pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated degradation (ERAD), within POMC neurons. Mice with POMC neuron–specific Sel1L deficiency developed age-associated obesity due, at least in part, to the ER retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a fraction of nascent POMC molecules for ubiquitination and proteasomal degradation, preventing accumulation of misfolded and aggregated POMC, thereby ensuring that another fraction of POMC can undergo normal posttranslational processing and trafficking for secretion. Moreover, we found that the disease-associated POMC-C28F mutant evades ERAD and becomes aggregated due to the presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this study not only identifies ERAD as an important mechanism regulating POMC maturation within the ER, but also provides insights into the pathogenesis of monogenic obesity associated with defective prohormone folding. PMID:29457782

Kinetic control over pathway complexity in supramolecular polymerization through modulating the energy landscape by rational molecular design.

PubMed

Ogi, Soichiro; Fukui, Tomoya; Jue, Melinda L; Takeuchi, Masayuki; Sugiyasu, Kazunori

2014-12-22

Far-from-equilibrium thermodynamic systems that are established as a consequence of coupled equilibria are the origin of the complex behavior of biological systems. Therefore, research in supramolecular chemistry has recently been shifting emphasis from a thermodynamic standpoint to a kinetic one; however, control over the complex kinetic processes is still in its infancy. Herein, we report our attempt to control the time evolution of supramolecular assembly in a process in which the supramolecular assembly transforms from a J-aggregate to an H-aggregate over time. The transformation proceeds through a delicate interplay of these two aggregation pathways. We have succeeded in modulating the energy landscape of the respective aggregates by a rational molecular design. On the basis of this understanding of the energy landscape, programming of the time evolution was achieved through adjusting the balance between the coupled equilibria. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Binding Patterns Associated Aß-HSP60 p458 Conjugate to HLA-DR-DRB Allele of Human in Alzheimer's Disease: An In Silico Approach.

PubMed

Padmadas, Naveen; Panda, Pritam Kumar; Durairaj, Sudarsanam

2018-03-01

Alzheimer's disease (AD) is a complex, irreversible, progressive brain disorder, which diminishes memory in a slow pace and thinking skills; ranked third by experts. It is a complex disorder that involves numerous cellular and subcellular alterations. The pathogenesis of AD is still unknown, but for better understanding, we proposed an in silico analysis to find out the binding patterns associated with HSP60. Several experimental conclusions have been drawn to understand the actual mechanism behind the forming of aggregation due to misfolding. Protein misfolding disorder is experimentally identified by the accumulation of protein aggregates at the intracellular or extracellular region of brain that adversely affects the cell functioning by disrupting the connection between the cells and ultimately leading to cell death. To unravel the mystery behind the mechanism of AD through computational approach, the current proposal shows the designing of Aß-HSP60 p458 conjugate followed by secondary structure analysis, which is further targeted to HLA-DR-DRB allele of human. The antigenicity of Aß (1-42) peptide is the major concern in our study predicted through PVS server, which provides an insight into the immunogenic behavior of Aß peptide. The mechanism involved in the interaction of HSP60-Aß conjugate with HLA-DR-DRB allele considering the fact that Aß (1-42) is highly immunogenic in human and interactions evoked highly robust T-cell response through MHC class II binding predictions. It was assisted by molecular dynamics simulation of predicted HSP60 structure followed by validation through Ramachandran plot analysis and protein-protein interaction of Aß (1-42) with HSP60.

Study on Mechanical Properties of Concrete Using Plastic Waste as an Aggregate

NASA Astrophysics Data System (ADS)

Jaivignesh, B.; Sofi, A.

2017-07-01

Disposal of large quantity of plastic causes land, water and air pollution etc.., so a study is conducted to recycle the plastic in concrete. This work investigates about the replacement of natural aggregate with non-biodegradable plastic aggregate made up of mixed plastic waste in concrete. Several tests are conducted such as compressive strength of cube, split tensile strength of cylinder, flexural strength test of prism to identify the properties and behavior of concrete using plastic aggregate. Replacement of fine aggregate weight by 10%, 15%, 20% with Plastic fine (PF) aggregate and for each replacement of fine aggregate 15%, 20%, 25% of coarse aggregate replacement also conducted with Plastic Coarse(PC) aggregate. In literatures reported that the addition of plastic aggregate in concrete causes the reduction of strength in concrete due to poor bonding between concrete and plastic aggregate, so addition of 0.3% of steel fiber by weight of cement in concrete is done to improve the concrete strength. Totally 60 cubes, 60 cylinders and 40 prisms are casted to identify the compressive strength, split tensile strength and flexural strength respectively. Casted specimens are tested at 7 and 28 days. The identified results from concrete using plastic aggregate are compared with conventional concrete. Result shows that reduction in mechanical properties of plastic aggregate added concrete. This reduction in strength is mainly due to poor bond strength between cement and plastic aggregate.

W-band EPR of vanadyl complexes aggregates on the surface of Al2O3

NASA Astrophysics Data System (ADS)

Mamin, G.; Gafurov, M.; Galukhin, A.; Gracheva, I.; Murzakhanov, F.; Rodionov, A.; Orlinskii, S.

2018-05-01

Structural characterization of metalloporphyrins, asphaltenes and their aggregates in complex systems such as native hydrocarbons is in the focus of scientific and industrial interests since many years. We present W-band (95 GHz) electron paramagnetic resonance (EPR) study in the magnetic field of about 3.4 T and temperature of 100 K for Karmalinskoe oil, asphaltens and asphaltenes deposited on the surface of Al2O3. Features of the obtained spectra are described. Shift to the higher frequencies allows to separate spectrally the contributions from paramagnetic complexes of different origin and define the EPR parameters more accurately comparing to the conventional X-band (9 GHz). Changes of the EPR parameters are tracked. We suggest that the proposed approach can be used for the investigation of structure of vanadyl complexes aggregates in crude oil and their fractions.

Nanofibers formed through pi...pi stacking of the complexes of glucosyl-C2-salicyl-imine and phenylalanine: characterization by microscopy, modeling by molecular mechanics, and interaction by alpha-helical and beta-sheet proteins.

PubMed

Acharya, Amitabha; Ramanujam, Balaji; Mitra, Atanu; Rao, Chebrolu P

2010-07-27

This paper deals with the self-assembly of the 1:1 complex of two different amphiphiles, namely, a glucosyl-salicyl-imino conjugate (L) and phenylalanine (Phe), forming nanofibers over a period of time through pi...pi interactions. Significant enhancement observed in the fluorescence intensity of L at approximately 423 nm band and the significant decrease observed in the absorbance of the approximately 215 nm band are some characteristics of this self-assembly. Matrix-assisted laser desorption ionization/time of flight titration carried out at different time intervals supports the formation of higher aggregates. Atomic force microscopy (AFM), transmission electron microscopy, and scanning electron miscroscopy results showed the formation of nanofibers for the solutions of L with phenylalanine. In dynamic light scattering measurements, the distribution of the particles extends to a higher diameter range over time, indicating a slow kinetic process of assembly. Similar spectral and microscopy studies carried out with the control molecules support the role of the amino acid moiety over the simple -COOH moiety as well as the side chain phenyl moiety in association with the amino acid, in the formation of these fibers. All these observations support the presence of pi...pi interactions between the initially formed 1:1 complexes leading to the fiber formation. The aggregation of 1:1 complexes leading to fibers followed by the formation of bundles has been modeled by molecular mechanics studies. Thus the fiber formation with L is limited to phenylalanine and not to any other naturally occurring amino acid and hence a polymer composed of two different biocompatible amphiphiles. AFM studies carried out between the fiber forming mixture and proteins resulted in the observation that only BSA selectively adheres to the fiber among the three alpha-helical and two beta-sheet proteins studied and hence may be of use in some medical applications.

Mechanical Dissociation of Platelet Aggregates in Blood Stream

NASA Astrophysics Data System (ADS)

Hoore, Masoud; Fedosov, Dmitry A.; Gompper, Gerhard; Complex; Biological Fluids Group Team

2017-11-01

von Willebrand factor (VWF) and platelet aggregation is a key phenomenon in blood clotting. These aggregates form critically in high shear rates and dissolve reversibly in low shear rates. The emergence of a critical shear rate, beyond which aggregates form and below which they dissolve, has an interesting impact on aggregation in blood flow. As red blood cells (RBCs) migrate to the center of the vessel in blood flow, a RBC free layer (RBC-FL) is left close to the walls into which the platelets and VWFs are pushed back from the bulk flow. This margination process provides maximal VWF-platelet aggregation probability in the RBC-FL. Using mesoscale hydrodynamic simulations of aggregate dynamics in blood flow, it is shown that the aggregates form and grow in RBC-FL wherein shear rate is high for VWF stretching. By growing, the aggregates penetrate to the bulk flow and get under order of magnitude lower shear rates. Consequently, they dissolve and get back into the RBC-FL. This mechanical limitation for aggregates prohibits undesired thrombosis and vessel blockage by aggregates, while letting the VWFs and platelets to aggregate close to the walls where they are actually needed. The support by the DFG Research Unit FOR 1543 SHENC and CPU time Grant by the Julich Supercomputing Center are acknowledged.

Aub and Ago3 are recruited to nuage through two mechanisms to form a ping-pong complex assembled by Krimper

PubMed Central

Webster, Alexandre; Li, Sisi; Hur, Junho K.; Wachsmuth, Malte; Bois, Justin S.; Perkins, Edward M.; Patel, Dinshaw J.; Aravin, Alexei A.

2015-01-01

In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3) localize to perinuclear ‘nuage’ granules and use guide piRNAs to target and destroy transposable element transcripts. We find that Aub and Ago3 are recruited to nuage by two different mechanisms. Aub requires a piRNA guide for nuage recruitment, indicating that its localization depends on recognition of RNA targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on interaction with Krimper, a stable component of nuage that is able to aggregate in the absence of other nuage proteins. We show that Krimper interacts directly with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact with Krimper, but are dispensable for Ago3 to bind Krimper. Our study reveals a multi-step process responsible for the assembly and function of nuage complexes in piRNA-guided transposon repression. PMID:26295961

Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle.

PubMed

Li, Zhuo; Hartl, F Ulrich; Bracher, Andreas

2013-08-01

The Hsp70-interacting protein, Hip, cooperates with the chaperone Hsp70 in protein folding and prevention of aggregation. Hsp70 interacts with non-native protein substrates in an ATP-dependent reaction cycle regulated by J-domain proteins and nucleotide exchange factors (NEFs). Hip is thought to delay substrate release by slowing ADP dissociation from Hsp70. Here we present crystal structures of the dimerization domain and the tetratricopeptide repeat (TPR) domain of rat Hip. As shown in a cocrystal structure, the TPR core of Hip interacts with the Hsp70 ATPase domain through an extensive interface, to form a bracket that locks ADP in the binding cleft. Hip and NEF binding to Hsp70 are mutually exclusive, and thus Hip attenuates active cycling of Hsp70-substrate complexes. This mechanism explains how Hip enhances aggregation prevention by Hsp70 and facilitates transfer of specific proteins to downstream chaperones or the proteasome.

Discerning regulation of cis- and trans-presentation of CD8+ T-cell epitopes by EBV-encoded oncogene LMP-1 through self-aggregation.

PubMed

Smith, Corey; Wakisaka, Naohiro; Crough, Tania; Peet, Jesse; Yoshizaki, Tomokazu; Beagley, Leone; Khanna, Rajiv

2009-06-11

Activation of the nuclear factor-kappaB pathway by Epstein-Barr virus-encoded latent membrane protein-1 (LMP-1) leads to an up-regulation of the major histocompatibility complex class I antigen-processing pathway. Paradoxically, LMP-1 itself induces a subdominant CD8+ T-cell response and appears to have evolved to avoid immune recognition. Here we show that, although expression of LMP-1 in human cells dramatically enhanced the trans-presentation of CD8+ T-cell epitopes, cis-presentation of LMP-1-derived epitopes was severely impaired. Testing of a series of LMP-1 mutants revealed that deletion of the first transmembrane domain of LMP-1, which prevented self-aggregation, significantly enhanced cis-presentation of T-cell epitopes from this protein, whereas it lost its ability to up-regulate trans-presentation. Interestingly, we also found that cis-presentation of LMP-1 epitopes was rescued by blocking the proteasome function. Taken together, these results delineate a novel mechanism of immune evasion, which renders a virally encoded oncogene inaccessible to the conventional major histocompatibility complex class I pathway limiting its cis-presentation to effector cells.

Soot superaggregates from flaming wildfires and their direct radiative forcing.

PubMed

Chakrabarty, Rajan K; Beres, Nicholas D; Moosmüller, Hans; China, Swarup; Mazzoleni, Claudio; Dubey, Manvendra K; Liu, Li; Mishchenko, Michael I

2014-07-01

Wildfires contribute significantly to global soot emissions, yet their aerosol formation mechanisms and resulting particle properties are poorly understood and parameterized in climate models. The conventional view holds that soot is formed via the cluster-dilute aggregation mechanism in wildfires and emitted as aggregates with fractal dimension Df ≈ 1.8 mobility diameter Dm ≤ 1 μm, and aerodynamic diameter Da ≤ 300 nm. Here we report the ubiquitous presence of soot superaggregates (SAs) in the outflow from a major wildfire in India. SAs are porous, low-density aggregates of cluster-dilute aggregates with characteristic Df ≈ 2.6, Dm > 1 μm, and Da ≤ 300 nm that form via the cluster-dense aggregation mechanism. We present additional observations of soot SAs in wildfire smoke-laden air masses over Northern California, New Mexico, and Mexico City. At 550 nm wavelength, [corrected] we estimate that SAs contribute, per unit optical depth, up to 35% less atmospheric warming than freshly-emitted (D(f) ≈ 1.8) [corrected] aggregates, and ≈90% more warming than the volume-equivalent spherical soot particles simulated in climate models.

The Mechanisms of Aberrant Protein Aggregation

NASA Astrophysics Data System (ADS)

Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

2012-02-01

We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders.

PubMed

Caughey, Byron; Lansbury, Peter T

2003-01-01

Many neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates.

Soot superaggregates from flaming wildfires and their direct radiative forcing

PubMed Central

Chakrabarty, Rajan K.; Beres, Nicholas D.; Moosmüller, Hans; China, Swarup; Mazzoleni, Claudio; Dubey, Manvendra K.; Liu, Li; Mishchenko, Michael I.

2014-01-01

Wildfires contribute significantly to global soot emissions, yet their aerosol formation mechanisms and resulting particle properties are poorly understood and parameterized in climate models. The conventional view holds that soot is formed via the cluster-dilute aggregation mechanism in wildfires and emitted as aggregates with fractal dimension Df ≈ 1.8 mobility diameter Dm ≤ 1 μm, and aerodynamic diameter Da ≤ 300 nm. Here we report the ubiquitous presence of soot superaggregates (SAs) in the outflow from a major wildfire in India. SAs are porous, low-density aggregates of cluster-dilute aggregates with characteristic Df ≈ 2.6, Dm > 1 μm, and Da ≤ 300 nm that form via the cluster-dense aggregation mechanism. We present additional observations of soot SAs in wildfire smoke-laden air masses over Northern California, New Mexico, and Mexico City. We estimate that SAs contribute, per unit optical depth, up to 35% less atmospheric warming than freshly-emitted (Df ≈ 1.8) aggregates, and ≈90% more warming than the volume-equivalent spherical soot particles simulated in climate models. PMID:24981204

Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00215g Click here for additional data file.

PubMed Central

Meisl, Georg; Yang, Xiaoting

2017-01-01

The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42. PMID:28979758

Carbon Nanotubes, Nanocrystal Forms, and Complex Nanoparticle Aggregates in common fuel-gas combustion sources and the ambient air

NASA Astrophysics Data System (ADS)

Murr, L. E.; Bang, J. J.; Esquivel, E. V.; Guerrero, P. A.; Lopez, D. A.

2004-06-01

Aggregated multiwall carbon nanotubes (with diameters ranging from ˜3 to 30nm) and related carbon nanocrystal forms ranging in size from 0.4 to 2 μm (average diameter) have been collected in the combustion streams for methane/air, natural gas/air, and propane gas/air flames using a thermal precipitator. Individual particle aggregates were collected on carbon/formvar-coated 3mm nickel grids and examined in a transmission electron microscope, utilizing bright-field imaging, selected-area electron diffraction analysis, and energy-dispersive X-ray spectrometry techniques. The natural gas and propane gas sources were domestic (kitchen) stoves, and similar particle aggregates collected in the outdoor air were correspondingly identified as carbon nanocrystal aggregates and sometimes more complex aggregates of silica nanocrystals intermixed with the carbon nanotubes and other carbon nanocrystals. Finally, and in light of the potential for methane-series gas burning as major sources of carbon nanocrystal aggregates in both the indoor and outdoor air, data for natural gas consumption and corresponding asthma deaths and incidence are examined with a degree of speculation regarding any significance in the correlations.

The Chameleonic Nature of Platinum(II) Imidazopyridine Complexes.

PubMed

Pinter, Piermaria; Pittkowski, Rebecca; Soellner, Johannes; Strassner, Thomas

2017-10-12

The synthesis and characterization of cyclometalated C^C* platinum(II) complexes with unique photophysical properties, aggregation induced enhancement of the quantum yields with a simultaneous decrease of phosphorescence lifetimes, is reported. Additionally, a change of emission color is induced by variation of the excitation wavelength. The aggregation behavior of these complexes is controlled by the steric demand of the substituents. The photophysical properties of these complexes are investigated through emission-excitation matrix analysis (EEM). The monomeric complexes are excellent room temperature phosphorescent blue emitters with emission maxima below 470 nm and quantum yields of up to 93 %. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface Complexation Modeling of Eu(III) and U(VI) Interactions with Graphene Oxide.

PubMed

Xie, Yu; Helvenston, Edward M; Shuller-Nickles, Lindsay C; Powell, Brian A

2016-02-16

Graphene oxide (GO) has great potential for actinide removal due to its extremely high sorption capacity, but the mechanism of sorption remains unclear. In this study, the carboxylic functional group and an unexpected sulfonate functional group on GO were characterized as the reactive surface sites and quantified via diffuse layer modeling of the GO acid/base titrations. The presence of sulfonate functional group on GO was confirmed using elemental analysis and X-ray photoelectron spectroscopy. Batch experiments of Eu(III) and U(VI) sorption to GO as the function of pH (1-8) and as the function of analyte concentration (10-100, 000 ppb) at a constant pH ≈ 5 were conducted; the batch sorption results were modeled simultaneously using surface complexation modeling (SCM). The SCM indicated that Eu(III) and U(VI) complexation to carboxylate functional group is the main mechanism for their sorption to GO; their complexation to the sulfonate site occurred at the lower pH range and the complexation of Eu(III) to sulfonate site are more significant than that of U(VI). Eu(III) and U(VI) facilitated GO aggregation was observed with high Eu(III) and U(VI) concentration and may be caused by surface charge neutralization of GO after sorption.

Molecular investigation on the binding of Cd(II) by the binary mixtures of montmorillonite with two bacterial species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Huihui; Qu, ChenChen; Liu, Jing

Bacteria and phyllosilicate commonly coexist in the natural environment, producing various bacteria–clay complexes that are capable of immobilizing heavy metals, such as cadmium, via adsorption. However, the molecular binding mechanisms of heavy metals on these complex aggregates still remain poorly understood. This study investigated Cd adsorption on Gram-positive B. subtilis, Gram-negative P. putida and their binary mixtures with montmorillonite (Mont) using the Cd K-edge x-ray absorption spectroscopy (XAS) and isothermal titration calorimetry (ITC). We observed a lower adsorptive capacity for P. putida than B. subtilis, whereas P. putida–Mont and B. subtilis–Mont mixtures showed nearly identical Cd adsorption behaviors. EXAFS fitsmore » and ITC measurements demonstrated more phosphoryl binding of Cd in P. putida. The decreased coordination of C atoms around Cd and the reduced adsorption enthalpies and entropies for the binary mixtures compared to that for individual bacteria suggested that the bidentate Cd-carboxyl complexes in pure bacteria systems were probably transformed into monodentate complexes that acted as ionic bridging structure between bacteria and motmorillonite. This study clarified the binding mechanism of Cd at the bacteria–phyllosilicate interfaces from a molecular and thermodynamic view, which has an environmental significance for predicting the chemical behavior of trace elements in complex mineral–organic systems.« less

Automated measurement of aggregate indices of shape

DOT National Transportation Integrated Search

1995-12-01

Aggregate angularity is a significant factor in determining pavement resistance to rutting. Determination of aggregate angularity by direct means allows a more meaningful study of the mechanisms of pavement deformation. However, direct techniques hav...

Fractal aggregates in tennis ball systems

NASA Astrophysics Data System (ADS)

Sabin, J.; Bandín, M.; Prieto, G.; Sarmiento, F.

2009-09-01

We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the images of the cluster of balls, following Forrest and Witten's pioneering studies on the aggregation of smoke particles, to estimate their fractal dimension.

Impact of Aggregates Size and Fibers on basic Mechanical Properties of Asphalt Emulsion—Cement Concrete

NASA Astrophysics Data System (ADS)

Fu, Jun; Liu, Zhihong; Liu, Jie

2018-01-01

Asphalt Emulsion—Cement Concrete (AECC) is currently considered as a typical semi-flexibility material. One of the disadvantages of this material is brittle fracture and lacking ductility. This study aims at accelerating the basic mechanical properties of AECC using fibers and different aggregates size. The mix of AECC was introduced and the different content of fibers and aggregates size were studied. The results showed that the smaller aggregates size could improve the young’s modulus and compressive strength as well as fiber. The modulus-compressive strength ratio of fiber reinforced AECC is always below 500.

Precursor Ion–Ion Aggregation in the Brust–Schiffrin Synthesis of Alkanethiol Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, Trent R.; Renslow, Ryan; Govind, Niranjan

Tetraoctylammonium bromide is used in the Brust-Schiffrin nanoparticle synthesis to phase-transfer chloroaurate ions from the aqueous phase to the organic phase. While it is established that the quaternary ammonium complex self-associates in the organic phase, the actual self-assembled structure is debated. We have confirmed the presence of ion-ion aggregates through quantitative 1H Nuclear Magnetic Resonance spectroscopy (NMR), pulsed field gradient, diffusion-ordered NMR (DOSY-NMR) and density functional theory (DFT) based NMR shift calculations. Tetraoctylammonium complexes (TOA-X, where X = Br, Cl, AuCl4-xBrx, AuBr4/Br and AuCl4-xBrx/Br) were investigated to measure the extraction of water into the organic phase. 1H NMR and DFTmore » based NMR shielding calculations indicated that deshielding of water is due to hydration of the anion and not the formation of the aqueous core of a reverse micelle. DOSYNMR results were consistent with the formation of small aggregates at typical Brust-Schiffrin synthesis concentrations. The extent of aggregation correlated with the size and electronegativity of the anion and was analyzed with a modified, isodesmic, indefinite aggregation model. The substitution of bromoauric acid for chlororoauric acid at conditions emulating the Brust-Schiffrin synthesis increased the aggregation of the quaternary ammonium complex. The increase in aggregation corresponded with an increase in the size of the produced nanoparticles from 4.3 to 4.6 nm. Understanding the selfassembly and supramolecular structure of precursors in the Brust-Schiffrin synthesis will enable further refinement of models that predict the growth of noble metal nanoparticles.« less

In vitro study of α-synuclein protofibrils by cryo-EM suggests a Cu(2+)-dependent aggregation pathway.

PubMed

Zhang, Hangyu; Griggs, Amy; Rochet, Jean-Christophe; Stanciu, Lia A

2013-06-18

The aggregation of α-synuclein is thought to play a role in the death of dopamine neurons in Parkinson's disease (PD). Alpha-synuclein transitions itself through an aggregation pathway consisting of pathogenic species referred to as protofibrils (or oligomer), which ultimately convert to mature fibrils. The structural heterogeneity and instability of protofibrils has significantly impeded advance related to the understanding of their structural characteristics and the amyloid aggregation mystery. Here, we report, to our knowledge for the first time, on α-synuclein protofibril structural characteristics with cryo-electron microscopy. Statistical analysis of annular protofibrils revealed a constant wall thickness as a common feature. The visualization of the assembly steps enabled us to propose a novel, to our knowledge, mechanisms for α-synuclein aggregation involving ring-opening and protofibril-protofibril interaction events. The ion channel-like protofibrils and their membrane permeability have also been found in other amyloid diseases, suggesting a common molecular mechanism of pathological aggregation. Our direct visualization of the aggregation pathway of α-synuclein opens up fresh opportunities to advance the understanding of protein aggregation mechanisms relevant to many amyloid diseases. In turn, this information would enable the development of additional therapeutic strategies aimed at suppressing toxic protofibrils of amyloid proteins involved in neurological disorders. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mechanisms of m-cresol induced protein aggregation studied using a model protein cytochrome c†

PubMed Central

Singh, Surinder M.; Hutchings, Regina L.; Mallela, Krishna M.G.

2014-01-01

Multi-dose protein formulations require an effective antimicrobial preservative (AP) to inhibit microbial growth during long-term storage of unused formulations. m-cresol is one such AP, but has been shown to cause protein aggregation. However, the fundamental physical mechanisms underlying such AP-induced protein aggregation are not understood. In this study, we used a model protein cytochrome c to identify the protein unfolding that triggers protein aggregation. m-cresol induced cytochrome c aggregation at preservative concentrations that are commonly used to inhibit microbial growth. Addition of m-cresol decreased the temperature at which the protein aggregated and increased the aggregation rate. However, m-cresol did not perturb the tertiary or secondary structure of cytochrome c. Instead, it populated an “invisible” partially unfolded intermediate where a local protein region around the methionine residue at position 80 was unfolded. Stabilizing the Met80 region drastically decreased the protein aggregation, which conclusively shows that this local protein region acts as an aggregation “hot-spot”. Based on these results, we propose that APs induce protein aggregation by partial rather than global unfolding. Because of the availability of site-specific probes to monitor different levels of protein unfolding, cytochrome c provided a unique advantage in characterizing the partial protein unfolding that triggers protein aggregation. PMID:21229618

Effect of point defects on the amorphization of metallic alloys during ion implantation. [NiTi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedraza, D.F.; Mansur, L.K.

1985-01-01

A theoretical model of radiation-induced amorphization of ordered intermetallic compounds is developed. The mechanism is proposed to be the buildup of lattice defects to very high concentrations, which destabilizes the crystalline structure. Because simple point defects do not normally reach such levels during irradiation, a new defect complex containing a vacancy and an interstitial is hypothesized. Crucial properties of the complex are that the interstitial sees a local chemical environment similar to that of an atom in the ordered lattice, that the formation of the complex prevents mutual recombination and that the complex is immobile. The evolution of a disordermore » based on complexes is not accompanied by like point defect aggregation. The latter leads to the development of a sink microstructure in alloys that do not become amorphous. For electron irradiation, the complexes form by diffusional encounters. For ion irradiation, complexes are also formed directly in cascades. The possibility of direct amorphization in cascades is also included. Calculations for the compound NiTi show reasonable agreement with measured amorphization kinetics.« less

PsbS protein modulates non-photochemical chlorophyll fluorescence quenching in membranes depleted of photosystems.

PubMed

Ware, Maxwell A; Giovagnetti, Vasco; Belgio, Erica; Ruban, Alexander V

2015-11-01

Plants with varying levels of PsbS protein were grown on lincomycin. Enhanced levels of non-photochemical fluorescence quenching (NPQ) in over-expressers of the protein have been observed. This was accompanied by increased amplitude of the irreversible NPQ component, qI, previously considered to reflect mainly photoinhibition of PSII reaction centres (RCII). However, since RCIIs were largely absent the observed qI is likely to originate from the LHCII antenna. In chloroplasts of over-expressers of PsbS grown on lincomycin an abnormally large NPQ (∼7) was characterised by a 0.34 ns average chlorophyll fluorescence lifetime. Yet the lifetime in the Fm state was similar to that of wild-type plants. 77K fluorescence emission spectra revealed a specific 700 nm peak typical of LHCII aggregates as well as quenching of the PSI fluorescence at 730 nm. The aggregated state manifested itself as a clear change in the distance between LHCII complexes detected by freeze-fracture electron microscopy. Grana thylakoids in the quenched state revealed 3 times more aggregated LHCII particles compared to the dark-adapted state. Overall, the results directly demonstrate the importance of LHCII aggregation in the NPQ mechanism and show that the PSII supercomplex structure plays no role in formation of the observed quenching. Copyright © 2015 Elsevier B.V. All rights reserved.

Hydrothermal growth of cross-linked hyperbranched copper dendrites using copper oxalate complex

NASA Astrophysics Data System (ADS)

Truong, Quang Duc; Kakihana, Masato

2012-06-01

A facile and surfactant-free approach has been developed for the synthesis of cross-linked hyperbranched copper dendrites using copper oxalate complex as a precursor and oxalic acid as a reducing and structure-directing agent. The synthesized particles are composed of highly branched nanostructures with unusual cross-linked hierarchical networks. The formation of copper dendrites can be explained in view of both diffusion control and aggregation-based growth model accompanied by the chelation-assisted assembly. Oxalic acid was found to play dual roles as reducing and structure-directing agent based on the investigation results. The understanding on the crystal growth and the roles of oxalic acid provides clear insight into the formation mechanism of hyperbranched metal dendrites.

Thermodynamic criteria analysis for the use of taro starch spherical aggregates as microencapsulant matrix.

PubMed

Hoyos-Leyva, Javier D; Bello-Pérez, Luis A; Alvarez-Ramirez, J

2018-09-01

Spherical aggregates can be obtained from taro starch by spray-drying without using bonding agents. Accurate information about thermal issues of spherical aggregates can provide valuable information for assessing the application as encapsulant. Spherical aggregates of taro starch were obtained by spray-drying and analyzed using dynamic vapour sorption. The use of the Guggenheim, Anderson and de Boer (GAB) model indicated a Type II isotherm pattern with weaker interactions in the multilayer region. Differential enthalpy and entropy estimates reflected a mesoporous microstructure, implying that energetic mechanisms dominate over transport mechanisms in the sorption process. The limitation by energetic mechanisms was corroborated with enthalpy-entropy compensation estimates. The diffusivity coefficient was of the order of 10 -8  m 2 ·s -1 , which is in line with results obtained for common materials used for encapsulation purposes. The thermodynamic properties and the lack of a bonding agent indicated the viability of spherical aggregates of taro starch for encapsulation of biocompounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modeling phase separation in mixtures of intrinsically-disordered proteins

NASA Astrophysics Data System (ADS)

Gu, Chad; Zilman, Anton

Phase separation in a pure or mixed solution of intrinsically-disordered proteins (IDPs) and its role in various biological processes has generated interest from the theoretical biophysics community. Phase separation of IDPs has been implicated in the formation of membrane-less organelles such as nucleoli, as well as in a mechanism of selectivity in transport through the nuclear pore complex. Based on a lattice model of polymers, we study the phase diagram of IDPs in a mixture and describe the selective exclusion of soluble proteins from the dense-phase IDP aggregates. The model captures the essential behaviour of phase separation by a minimal set of coarse-grained parameters, corresponding to the average monomer-monomer and monomer-protein attraction strength, as well as the protein-to-monomer size ratio. Contrary to the intuition that strong monomer-monomer interaction increases exclusion of soluble proteins from the dense IDP aggregates, our model predicts that the concentration of soluble proteins in the aggregate phase as a function of monomer-monomer attraction is non-monotonic. We corroborate the predictions of the lattice model using Langevin dynamics simulations of grafted polymers in planar and cylindrical geometries, mimicking various in-vivo and in-vitro conditions.

Directional virtual backbone based data aggregation scheme for Wireless Visual Sensor Networks.

PubMed

Zhang, Jing; Liu, Shi-Jian; Tsai, Pei-Wei; Zou, Fu-Min; Ji, Xiao-Rong

2018-01-01

Data gathering is a fundamental task in Wireless Visual Sensor Networks (WVSNs). Features of directional antennas and the visual data make WVSNs more complex than the conventional Wireless Sensor Network (WSN). The virtual backbone is a technique, which is capable of constructing clusters. The version associating with the aggregation operation is also referred to as the virtual backbone tree. In most of the existing literature, the main focus is on the efficiency brought by the construction of clusters that the existing methods neglect local-balance problems in general. To fill up this gap, Directional Virtual Backbone based Data Aggregation Scheme (DVBDAS) for the WVSNs is proposed in this paper. In addition, a measurement called the energy consumption density is proposed for evaluating the adequacy of results in the cluster-based construction problems. Moreover, the directional virtual backbone construction scheme is proposed by considering the local-balanced factor. Furthermore, the associated network coding mechanism is utilized to construct DVBDAS. Finally, both the theoretical analysis of the proposed DVBDAS and the simulations are given for evaluating the performance. The experimental results prove that the proposed DVBDAS achieves higher performance in terms of both the energy preservation and the network lifetime extension than the existing methods.

Memantine inhibits β-amyloid aggregation and disassembles preformed β-amyloid aggregates.

PubMed

Takahashi-Ito, Kaori; Makino, Mitsuhiro; Okado, Keiko; Tomita, Taisuke

2017-11-04

Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect Aβ aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of Aβ aggregates, including Aβs carrying familial AD mutations, and disaggregated preformed Aβ(1-42) fibrils. These results suggest that the inhibition of Aβ aggregation and induction of Aβ disaggregation may be involved in the mechanisms by which memantine reduces Aβ deposition in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations.

PubMed

Liao, Chenyi; Esai Selvan, Myvizhi; Zhao, Jun; Slimovitch, Jonathan L; Schneebeli, Severin T; Shelley, Mee; Shelley, John C; Li, Jianing

2015-08-20

Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observed—for the first time in atomistic detail—that four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety.

Molecular chaperone properties of the high molecular weight aggregate from aged lens

NASA Technical Reports Server (NTRS)

Takemoto, L.; Boyle, D.; Spooner, B. S. (Principal Investigator)

1994-01-01

The high molecular weight aggregate (HMWA) fraction was isolated from the water soluble proteins of aged bovine lenses. Its composition and ability to inhibit heat-induced denaturation and aggregation were compared with the lower molecular weight, oligomeric fraction of alpha isolated from the same lens. Although the major components of both fractions were the alpha-A and alpha-B chains, the HMWA fraction possessed a decreased ability to protect other proteins against heat-induced denaturation and aggregation. Immunoelectron microscopy of both fractions demonstrated that alpha particles from the HMWA fraction contained increased amounts of beta and gamma crystallins, bound to a central region of the supramolecular complex. Together, these results demonstrate that alpha crystallins found in the HMWA fraction possess a decreased ability to protect against heat-induced denaturation and aggregation, and suggest that at least part of this decrease could be due to the increased presence of beta and gamma crystallins complexed to the putative chaperone receptor site of the alpha particles.

Aggregate Exposure Pathways in Support of Risk Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Yu-Mei; Leonard, Jeremy A.; Edwards, Stephen

Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluation of multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand the complex mechanisms that influence risk of chemical and non-chemical stressors, beginning at their source and ending at a biological endpoint relevant to human or ecosystem health risk assessment. Just as the Adverse Outcome Pathway (AOP) framework has emerged as a means of providing insight into mechanism-based toxicity, the exposure science community has seen the recent introduction of themore » Aggregate Exposure Pathway (AEP) framework. AEPs aid in making exposure data applicable to the FAIR (i.e., findable, accessible, interoperable, and reusable) principle, especially by (1) organizing continuous flow of disjointed exposure information;(2) identifying data gaps, to focus resources on acquiring the most relevant data; (3) optimizing use and repurposing of existing exposure data; and (4) facilitating interoperability among predictive models. Herein, we discuss integration of the AOP and AEP frameworks and how such integration can improve confidence in both traditional and cumulative risk assessment approaches.« less

Aggregate Exposure Pathways in Support of Risk Assessment

DOE PAGES

Tan, Yu-Mei; Leonard, Jeremy A.; Edwards, Stephen; ...

2018-03-29

Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluation of multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand the complex mechanisms that influence risk of chemical and non-chemical stressors, beginning at their source and ending at a biological endpoint relevant to human or ecosystem health risk assessment. Just as the Adverse Outcome Pathway (AOP) framework has emerged as a means of providing insight into mechanism-based toxicity, the exposure science community has seen the recent introduction of themore » Aggregate Exposure Pathway (AEP) framework. AEPs aid in making exposure data applicable to the FAIR (i.e., findable, accessible, interoperable, and reusable) principle, especially by (1) organizing continuous flow of disjointed exposure information;(2) identifying data gaps, to focus resources on acquiring the most relevant data; (3) optimizing use and repurposing of existing exposure data; and (4) facilitating interoperability among predictive models. Herein, we discuss integration of the AOP and AEP frameworks and how such integration can improve confidence in both traditional and cumulative risk assessment approaches.« less

In depth analysis of the quenching of three fluorene-phenylene-based cationic conjugated polyelectrolytes by DNA and DNA bases.

PubMed

Davies, Matthew L; Douglas, Peter; Burrows, Hugh D; Martincigh, Bice; Miguel, Maria da Graça; Scherf, Ullrich; Mallavia, Ricardo; Douglas, Alastair

2014-01-16

The interaction of three cationic poly {9,9-bis[N,N-(trimethylammonium)hexyl]fluorene-co-1,4-phenylene} polymers with average chain lengths of ∼6, 12, and 100 repeat units (PFP-NR36(I),12(Br),100(Br)) with both double and single stranded, short and long, DNA and DNA bases have been studied by steady state and time-resolved fluorescence techniques. Fluorescence of PFP-NR3 polymers is quenched with high efficiency by DNA (both double and single stranded) and DNA bases. The resulting quenching plots are sigmoidal and are not accurately described by using a Stern-Volmer quenching mechanism. Here, the quenching mechanism is well modeled in terms of an equilibrium in which a PFP-NR3/DNA aggregate complex is formed which brings polymer chains into close enough proximity to allow interchain excitation energy migration and quenching at aggregate or DNA base traps. Such an analysis gives equilibrium constants of 8.4 × 10(6) (±1.2 × 10(6)) M(-1) for short-dsDNA and 8.6 × 10(6) (±1.7 × 10(6)) M(-1) for short-ssDNA with PFP-NR36(I).

Using AFM to probe the complexation of DNA with anionic lipids mediated by Ca(2+): the role of surface pressure.

PubMed

Luque-Caballero, Germán; Martín-Molina, Alberto; Sánchez-Treviño, Alda Yadira; Rodríguez-Valverde, Miguel A; Cabrerizo-Vílchez, Miguel A; Maldonado-Valderrama, Julia

2014-04-28

Complexation of DNA with lipids is currently being developed as an alternative to classical vectors based on viruses. Most of the research to date focuses on cationic lipids owing to their spontaneous complexation with DNA. Nonetheless, recent investigations have revealed that cationic lipids induce a large number of adverse effects on DNA delivery. Precisely, the lower cytotoxicity of anionic lipids accounts for their use as a promising alternative. However, the complexation of DNA with anionic lipids (mediated by cations) is still in early stages and is not yet well understood. In order to explore the molecular mechanisms underlying the complexation of anionic lipids and DNA we proposed a combined methodology based on the surface pressure-area isotherms, Gibbs elasticity and Atomic Force Microscopy (AFM). These techniques allow elucidation of the role of the surface pressure in the complexation and visualization of the interfacial aggregates for the first time. We demonstrate that the DNA complexes with negatively charged model monolayers (DPPC/DPPS 4 : 1) only in the presence of Ca(2+), but is expelled at very high surface pressures. Also, according to the Gibbs elasticity plot, the complexation of lipids and DNA implies a whole fluidisation of the monolayer and a completely different phase transition map in the presence of DNA and Ca(2+). AFM imaging allows identification for the first time of specific morphologies associated with different packing densities. At low surface coverage, a branched net like structure is observed whereas at high surface pressure fibers formed of interfacial aggregates appear. In summary, Ca(2+) mediates the interaction between DNA and negatively charged lipids and also the conformation of the ternary system depends on the surface pressure. Such observations are important new generic features of the interaction between DNA and anionic lipids.

Protein-silver nanoparticle interactions to colloidal stability in acidic environments.

PubMed

Tai, Jui-Ting; Lai, Chao-Shun; Ho, Hsin-Chia; Yeh, Yu-Shan; Wang, Hsiao-Fang; Ho, Rong-Ming; Tsai, De-Hao

2014-11-04

We report a kinetic study of Ag nanoparticles (AgNPs) under acidic environments (i.e., pH 2.3 to pH ≈7) and systematically investigate the impact of protein interactions [i.e., bovine serum albumin (BSA) as representative] to the colloidal stability of AgNPs. Electrospray-differential mobility analysis (ES-DMA) was used to characterize the particle size distributions and the number concentrations of AgNPs. Transmission electron microscopy was employed orthogonally to provide visualization of AgNPs. For unconjugated AgNPs, the extent of aggregation, or the average particle size, was shown to be increased significantly with an increase of acidity, where a partial coalescence was found between the primary particles of unconjugated AgNP clusters. Aggregation rate constant, kD, was also shown to be proportional to acidity, following a correlation of log(kD) = -1.627(pH)-9.3715. Using ES-DMA, we observe BSA had a strong binding affinity (equilibrium binding constant, ≈ 1.1 × 10(6) L/mol) to the surface of AgNPs, with an estimated maximum molecular surface density of ≈0.012 nm(-2). BSA-functionalized AgNPs exhibited highly-improved colloidal stability compared to the unconjugated AgNPs under acidic environments, where both the acid-induced interfacial dissolution and the particle aggregation became negligible. Results confirm a complex mechanism of colloidal stability of AgNPs: the aggregation process was shown to be dominant, and the formation of BSA corona on AgNPs suppressed both particle aggregation and interfacial dissolution of AgNP samples under acidic environments.

Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

PubMed

Eisele, Yvonne S; Duyckaerts, Charles

2016-01-01

In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

NASA Astrophysics Data System (ADS)

Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

2016-08-01

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

Mechanical properties of concrete containing recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate replacement

NASA Astrophysics Data System (ADS)

Khalid, Faisal Sheikh; Azmi, Nurul Bazilah; Sumandi, Khairul Azwa Syafiq Mohd; Mazenan, Puteri Natasya

2017-10-01

Many construction and development activities today consume large amounts of concrete. The amount of construction waste is also increasing because of the demolition process. Much of this waste can be recycled to produce new products and increase the sustainability of construction projects. As recyclable construction wastes, concrete and ceramic can replace the natural aggregate in concrete because of their hard and strong physical properties. This research used 25%, 35%, and 45% recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate in producing concrete. Several tests, such as concrete cube compression and splitting tensile tests, were also performed to determine and compare the mechanical properties of the recycled concrete with those of the normal concrete that contains 100% natural aggregate. The concrete containing 35% RCA and 35% ceramic waste showed the best properties compared with the normal concrete.

Pullout resistance of mechanically stabilized earth wall steel strip reinforcement in uniform aggregate.

DOT National Transportation Integrated Search

2015-11-01

A wide range of reinforcement-backfill combinations have been used in mechanically stabilized earth (MSE) walls. Steel : strips are one type of reinforcement used to stabilize aggregate backfill through anchorage. In the current MSE wall design, pull...

E3 Ubiquitin Ligase CHIP and NBR1-Mediated Selective Autophagy Protect Additively against Proteotoxicity in Plant Stress Responses

PubMed Central

Qi, Jingxia; Chi, Yingjin; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2014-01-01

Plant stress responses require both protective measures that reduce or restore stress-inflicted damage to cellular structures and mechanisms that efficiently remove damaged and toxic macromolecules, such as misfolded and damaged proteins. We have recently reported that NBR1, the first identified plant autophagy adaptor with a ubiquitin-association domain, plays a critical role in plant stress tolerance by targeting stress-induced, ubiquitinated protein aggregates for degradation by autophagy. Here we report a comprehensive genetic analysis of CHIP, a chaperone-associated E3 ubiquitin ligase from Arabidopsis thaliana implicated in mediating degradation of nonnative proteins by 26S proteasomes. We isolated two chip knockout mutants and discovered that they had the same phenotypes as the nbr1 mutants with compromised tolerance to heat, oxidative and salt stresses and increased accumulation of insoluble proteins under heat stress. To determine their functional interactions, we generated chip nbr1 double mutants and found them to be further compromised in stress tolerance and in clearance of stress-induced protein aggregates, indicating additive roles of CHIP and NBR1. Furthermore, stress-induced protein aggregates were still ubiquitinated in the chip mutants. Through proteomic profiling, we systemically identified heat-induced protein aggregates in the chip and nbr1 single and double mutants. These experiments revealed that highly aggregate-prone proteins such as Rubisco activase and catalases preferentially accumulated in the nbr1 mutant while a number of light-harvesting complex proteins accumulated at high levels in the chip mutant after a relatively short period of heat stress. With extended heat stress, aggregates for a large number of intracellular proteins accumulated in both chip and nbr1 mutants and, to a greater extent, in the chip nbr1 double mutant. Based on these results, we propose that CHIP and NBR1 mediate two distinct but complementary anti-proteotoxic pathways and protein's propensity to aggregate under stress conditions is one of the critical factors for pathway selection of protein degradation. PMID:24497840

The roles of carbohydrates, proteins and lipids in the process of aggregation of natural marine organic matter investigated by means of 2D correlation spectroscopy applied to infrared spectra.

PubMed

Mecozzi, Mauro; Pietrantonio, Eva; Pietroletti, Marco

2009-01-01

In this paper the marine organic matter soluble in an alkaline medium called extractable humic substance (EHS), was extracted from three sediment samples of Tyrrhenian Sea and separated by precipitation at pH 2 in the two fractions of fulvic acids (FAs) and humic acids (HAs). FAs were further fractionated in seven sub-samples of different molecular weight (mw) by means of seven different ultrafiltration membranes operating in the range between mw<1 kDa and mw>100 kDa. Then the qualitative composition of each sample of fractionated FAs and HAs was studied by means of one-dimensional Fourier transform infrared spectroscopy in reflectance mode (FTIR-DRIFT) and by two-dimensional (2D) correlation spectroscopy both in wavelength-wavelength (WW) and in sample-sample (SS) mode. The application of 2D correlation WW spectroscopy allows to elucidate the different roles played by carbohydrates and proteins with respect to some lipid compounds such as fatty acids and ester fatty acids during the process of aggregate formations from mw approximately 1 kDa to higher size aggregates. In addition, 2D correlation WW spectroscopy allows to observe some peculiar interactions between carbohydrates and proteins in the formation of EHS aggregates, interactions which vary from a sample to another sample. The results of 2D correlation SS spectroscopy confirm the general evidences obtained by 2D WW spectroscopy and moreover, they also describe the formation of EHS aggregates as a complex process where evolutionary links and connectivity between aggregates of neighbour molecular size ranges are not evident. Two-dimensional correlation spectroscopy applied to FTIR spectroscopy shows to be a powerful tool for the investigation of the mechanisms involved in EHS aggregation because it supports the acquisition of structural information which sometimes can be hardly obtained by one-dimensional FTIR spectroscopy.

Low-refractive-index dye-aggregate films with small absorption based on anomalous dispersion.

PubMed

Wakamatsu, Takashi; Watanabe, Keita; Saito, Kazuhiro

2005-02-20

Complex-refractive-index spectra of Squarylium (SQ) dye-aggregate films deposited upon metal films have been investigated by measurements of properties of the films including absorption spectra (AS) and attenuated total reflection. Complex refractive indices are estimated by Kramers-Kronig analysis for the AS and by a theoretical curve-fitting analysis for attenuated total reflection. The dye-aggregate films exhibited an absorption that was blueshifted from that of a monomer, as a result of the H-aggregate formation of SQ molecules, and had a changing refractive index with anomalous dispersion about the H-absorption band. From both measurements of the SQ films it was found that there is a region of low absorption in the short-wavelength side of the absorption band and that the refractive index there is lower than that of glass.

Low-refractive-index dye-aggregate films with small absorption based on anomalous dispersion

NASA Astrophysics Data System (ADS)

Wakamatsu, Takashi; Watanabe, Keita; Saito, Kazuhiro

2005-02-01

Complex-refractive-index spectra of Squarylium (SQ) dye-aggregate films deposited upon metal films have been investigated by measurements of properties of the films including absorption spectra (AS) and attenuated total reflection. Complex refractive indices are estimated by Kramers-Kronig analysis for the AS and by a theoretical curve-fitting analysis for attenuated total reflection. The dye-aggregate films exhibited an absorption that was blueshifted from that of a monomer, as a result of the H-aggregate formation of SQ molecules, and had a changing refractive index with anomalous dispersion about the H-absorption band. From both measurements of the SQ films it was found that there is a region of low absorption in the short-wavelength side of the absorption band and that the refractive index there is lower than that of glass.

Hydrodynamic size-based separation and characterization of protein aggregates from total cell lysates

PubMed Central

Tanase, Maya; Zolla, Valerio; Clement, Cristina C; Borghi, Francesco; Urbanska, Aleksandra M; Rodriguez-Navarro, Jose Antonio; Roda, Barbara; Zattoni, Andrea; Reschiglian, Pierluigi; Cuervo, Ana Maria; Santambrogio, Laura

2016-01-01

Herein we describe a protocol that uses hollow-fiber flow field-flow fractionation (FFF) coupled with multiangle light scattering (MALS) for hydrodynamic size-based separation and characterization of complex protein aggregates. The fractionation method, which requires 1.5 h to run, was successfully modified from the analysis of protein aggregates, as found in simple protein mixtures, to complex aggregates, as found in total cell lysates. In contrast to other related methods (filter assay, analytical ultracentrifugation, gel electrophoresis and size-exclusion chromatography), hollow-fiber flow FFF coupled with MALS allows a flow-based fractionation of highly purified protein aggregates and simultaneous measurement of their molecular weight, r.m.s. radius and molecular conformation (e.g., round, rod-shaped, compact or relaxed). The polyethersulfone hollow fibers used, which have a 0.8-mm inner diameter, allow separation of as little as 20 μg of total cell lysates. In addition, the ability to run the samples in different denaturing and nondenaturing buffer allows defining true aggregates from artifacts, which can form during sample preparation. The protocol was set up using Paraquat-induced carbonylation, a model that induces protein aggregation in cultured cells. This technique will advance the biochemical, proteomic and biophysical characterization of molecular-weight aggregates associated with protein mutations, as found in many CNS degenerative diseases, or chronic oxidative stress, as found in aging, and chronic metabolic and inflammatory conditions. PMID:25521790

Zinc and cadmium complexes of a plant metallothionein under radical stress: desulfurisation reactions associated with the formation of trans-lipids in model membranes.

PubMed

Torreggiani, Armida; Domènech, Jordi; Orihuela, Ruben; Ferreri, Carla; Atrian, Sílvia; Capdevila, Mercè; Chatgilialoglu, Chryssostomos

2009-06-08

Metallothioneins (MTs) are sulfur-rich proteins capable of binding metal ions to give metal clusters. The metal-MT aggregates used in this work were Zn- and Cd-QsMT, where QsMT is an MT from the plant Quercus suber. Reactions of reductive reactive species (H(*) atoms and e(aq)(-)), produced by gamma irradiation of water, with Zn- and Cd-QsMT were carried out in both aqueous solutions and vesicle suspensions, and were characterized by different approaches. By using a biomimetic model based on unsaturated lipid vesicle suspensions, the occurrence of tandem protein/lipid damage was shown. The reactions of reductive reactive species with methionine residues and/or sulfur-containing ligands afford diffusible sulfur-centred radicals, which migrate from the aqueous phase to the lipid bilayer and transform the cis double bond of the oleate moiety into the trans isomer. Tailored experiments allowed the reaction mechanism to be elucidated in some detail. The formation of sulfur-centred radicals is accompanied by the modification of the metal-QsMT complexes, which were monitored by various spectroscopic and spectrometric techniques (Raman, CD, and ESI-MS). Attack of the H(*) atom and e(aq)(-) on the metal-QsMT aggregates can induce significant structural changes such as partial deconstruction and/or rearrangement of the metal clusters and breaking of the protein backbone. Substantial differences were observed in the behaviour of the Zn- and Cd-QsMT aggregates towards the reactive species, depending on the different folding of the polypeptide in these two cases.

The antimalarial activity of Ru–chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces

PubMed Central

Martínez, Alberto; Rajapakse, Chandima S. K.; Jalloh, Dalanda; Dautriche, Cula

2012-01-01

We have measured water/n-octanol partition coefficients, pKa values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium–πarene–chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied. PMID:19343380

The antimalarial activity of Ru-chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces.

PubMed

Martínez, Alberto; Rajapakse, Chandima S K; Jalloh, Dalanda; Dautriche, Cula; Sánchez-Delgado, Roberto A

2009-08-01

We have measured water/n-octanol partition coefficients, pK(a) values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium-pi-arene-chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied.

Insights into the Aggregation Mechanism of PolyQ Proteins with Different Glutamine Repeat Lengths.

PubMed

Yushchenko, Tetyana; Deuerling, Elke; Hauser, Karin

2018-04-24

Polyglutamine (polyQ) diseases, including Huntington's disease, result from the aggregation of an abnormally expanded polyQ repeat in the affected protein. The length of the polyQ repeat is essential for the disease's onset; however, the molecular mechanism of polyQ aggregation is still poorly understood. Controlled conditions and initiation of the aggregation process are prerequisites for the detection of transient intermediate states. We present an attenuated total reflection Fourier-transform infrared spectroscopic approach combined with protein immobilization to study polyQ aggregation dependent on the polyQ length. PolyQ proteins were engineered mimicking the mammalian N-terminus fragment of the Huntingtin protein and containing a polyQ sequence with the number of glutamines below (Q11), close to (Q38), and above (Q56) the disease threshold. A monolayer of the polyQ construct was chemically immobilized on the internal reflection element of the attenuated total reflection cell, and the aggregation was initiated via enzymatic cleavage. Structural changes of the polyQ sequence were monitored by time-resolved infrared difference spectroscopy. We observed faster aggregation kinetics for the longer sequences, and furthermore, we could distinguish β-structured intermediates for the different constructs, allowing us to propose aggregation mechanisms dependent on the repeat length. Q11 forms a β-structured aggregate by intermolecular interaction of stretched monomers, whereas Q38 and Q56 undergo conformational changes to various β-structured intermediates, including intramolecular β-sheets. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mechanochemical Preparation of Stable Sub-100 nm γ-Cyclodextrin:Buckminsterfullerene (C60) Nanoparticles by Electrostatic or Steric Stabilization.

PubMed

Van Guyse, Joachim F R; de la Rosa, Victor R; Hoogenboom, Richard

2018-02-21

Buckminster fullerene (C 60 )'s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C 60 is by complexation with γ-cyclodextrins. However, the formed complexes are not stable in time as they rapidly aggregate and eventually precipitate due to attractive intermolecular forces, a common problem in inclusion complexes of cyclodextrins. In this study we attempt to overcome the attractive intermolecular forces between the complexes by designing custom γ-cyclodextrin (γCD)-based supramolecular hosts for C 60 that inhibit the aggregation found in native γCD-C 60 complexes. The approach entails the introduction of either repulsive electrostatic forces or increased steric hindrance to prevent aggregation, thus enhancing the biomedical application potential of C 60 . These modifications have led to new sub-100 nm nanostructures that show long-term stability in solution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A possible molecular mechanism for the pressure reversal of general anaesthetics: Aggregation of halothane in POPC bilayers at high pressure

NASA Astrophysics Data System (ADS)

Tu, K. M.; Matubayasi, N.; Liang, K. K.; Todorov, I. T.; Chan, S. L.; Chau, P.-L.

2012-08-01

We placed halothane, a general anaesthetic, inside palmitoyloleoylphosphatidylcholine (POPC) bilayers and performed molecular dynamics simulations at atmospheric and raised pressures. We demonstrated that halothane aggregated inside POPC membranes at 20 MPa but not at 40 MPa. The pressure range of aggregation matches that of pressure reversal in whole animals, and strongly suggests that this could be the mechanism for this effect. Combining these results with previous experimental data, we describe a testable hypothesis of how aggregation of general anaesthetics at high pressure can lead to pressure reversal, the effect whereby these drugs lose the efficacy at high pressure.

Development of Fast Fourier Transform (FFT) micro-mechanical simulations of concrete specimens characterized by micro-X-ray fluorescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giorla, Alain B.

Concrete in Nuclear Power Plants (NPPs) can be exposed to a wide range of degradation phenomena. In the past years, the Light Water Reactor Sustainability (LWRS) program has investigated Radiation-Induced Volumetric Expansion (RIVE) as a potential degradation mechanism for concrete biological shields [Graves et al., 2014, Rosseel et al., 2016]. RIVE causes swelling and micro-mechanical damage in concrete due to the amorphization of mineral phases contained in the aggregates under neutron irradiation [Hilsdorf et al., 1978, Rosseel et al., 2016]. For long-term operations, it is critical to assess the durability of concrete after 60 or 80 years of exposure tomore » NPP operating conditions against this phenomenon. RIVE is dependent on the composition of the aggregates used in concrete. Quartz-bearing aggregates are more sensitive to RIVE than calcite-bearing aggregates, for example. However, the aggregate composition of a specific plant is generally not explicitly given in the concrete formulation, which makes it nearly impossible to predict the resistance of that concrete to RIVE. Additional characterization is needed to identify the radiation-sensitive mineral phases contained in the aggregates.« less

Rigidity of transmembrane proteins determines their cluster shape

NASA Astrophysics Data System (ADS)

Jafarinia, Hamidreza; Khoshnood, Atefeh; Jalali, Mir Abbas

2016-01-01

Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as α -helices and β -sheets have different structural rigidities. We use molecular dynamics simulation of a coarse-grained model of protein-embedded lipid membranes to investigate the mechanisms of protein clustering. For a variety of protein concentrations, our simulations under thermal equilibrium conditions reveal that the structural rigidity of transmembrane domains dramatically affects interactions and changes the shape of the cluster. We have observed stable large aggregates even in the absence of hydrophobic mismatch, which has been previously proposed as the mechanism of protein aggregation. According to our results, semiflexible proteins aggregate to form two-dimensional clusters, while rigid proteins, by contrast, form one-dimensional string-like structures. By assuming two probable scenarios for the formation of a two-dimensional triangular structure, we calculate the lipid density around protein clusters and find that the difference in lipid distribution around rigid and semiflexible proteins determines the one- or two-dimensional nature of aggregates. It is found that lipids move faster around semiflexible proteins than rigid ones. The aggregation mechanism suggested in this paper can be tested by current state-of-the-art experimental facilities.

Effect of Natural Organic Matter on Plutonium Sorption to Goethite

DOE PAGES

Conroy, Nathan A.; Zavarin, Mavrik; Kersting, Annie B.; ...

2016-11-21

For this research, the effect of citric acid (CA), desferrioxamine B (DFOB), fulvic acid (FA), and humic acid (HA) on plutonium (Pu) sorption to goethite was studied as a function of organic carbon concentration and pH using batch sorption experiments at 5 mg C·L –1 and 50 mg C·L –1 natural organic matter (NOM), 10 –9–10 –10 M 238Pu, and 0.1 g·L –1 goethite concentrations, at pH 3, 5, 7, and 9. Low sorption of ligands coupled with strong Pu complexation decreased Pu sorption at pH 5 and 7, relative to a ligand-free system. Conversely, CA, FA, and HA increasedmore » Pu sorption to goethite at pH 3, suggesting ternary complex formation or, in the case of humic acid, incorporation into HA aggregates. Mechanisms for ternary complex formation were characterized by Fourier transform infrared spectroscopy in the absence of Pu. CA and FA demonstrated clear surface interactions at pH 3, HA appeared unchanged suggesting HA aggregates had formed, and no DFOB interactions were observed. Plutonium sorption decreased in the presence of DFOB (relative to a ligand free system) at all pH values examined. Thus, DFOB does not appear to facilitate formation of ternary Pu-DFOB-goethite complexes. At pH 9, Pu sorption in the presence of all NOM increased relative to pH 5 and 7; speciation models attributed this to Pu(IV) hydrolysis competing with ligand complexation, increasing sorption. In conclusion, the results indicate that in simple Pu-NOM-goethite ternary batch systems, NOM will decrease Pu sorption to goethite at all but particularly low pH conditions.« less

Effect of Natural Organic Matter on Plutonium Sorption to Goethite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conroy, Nathan A.; Zavarin, Mavrik; Kersting, Annie B.

For this research, the effect of citric acid (CA), desferrioxamine B (DFOB), fulvic acid (FA), and humic acid (HA) on plutonium (Pu) sorption to goethite was studied as a function of organic carbon concentration and pH using batch sorption experiments at 5 mg C·L –1 and 50 mg C·L –1 natural organic matter (NOM), 10 –9–10 –10 M 238Pu, and 0.1 g·L –1 goethite concentrations, at pH 3, 5, 7, and 9. Low sorption of ligands coupled with strong Pu complexation decreased Pu sorption at pH 5 and 7, relative to a ligand-free system. Conversely, CA, FA, and HA increasedmore » Pu sorption to goethite at pH 3, suggesting ternary complex formation or, in the case of humic acid, incorporation into HA aggregates. Mechanisms for ternary complex formation were characterized by Fourier transform infrared spectroscopy in the absence of Pu. CA and FA demonstrated clear surface interactions at pH 3, HA appeared unchanged suggesting HA aggregates had formed, and no DFOB interactions were observed. Plutonium sorption decreased in the presence of DFOB (relative to a ligand free system) at all pH values examined. Thus, DFOB does not appear to facilitate formation of ternary Pu-DFOB-goethite complexes. At pH 9, Pu sorption in the presence of all NOM increased relative to pH 5 and 7; speciation models attributed this to Pu(IV) hydrolysis competing with ligand complexation, increasing sorption. In conclusion, the results indicate that in simple Pu-NOM-goethite ternary batch systems, NOM will decrease Pu sorption to goethite at all but particularly low pH conditions.« less

Bacteria rolling: motilities of rosette colonies in Caulobacter crescentus

NASA Astrophysics Data System (ADS)

Zeng, Yu; Liu, Bin

2016-11-01

The aquatic bacterium Caulobacter crescentus has two life cycle stages with distinct motilities: freely swimming swarmer cells and immotile stalked cells. Here, we show a new type of movement performed by freely suspended rosettes, spontaneous aggregates of stalked cells aligned radially relative to each other. Reproductive rosette members generate predivisional daughter cells with flagella, inducing rotations of the rosette as a whole. Such rotations exhibit dynamic angular velocities and lead to intermittent linear movements along liquid-solid interfaces, resembling rolling movements. We reconstructed the translational and rotational dynamics of the rosette movements from high-speed filming and long-term tracking. A mechanical model was developed to explain the hydrodynamic mechanism underlying such motilities. Our study illustrated a nontrivial mechanism for clustered bacteria to achieve motilities and sheds light on the adaptive significance of the collective behaviors of microorganisms in complex fluid environments.

New procyanidin B3-human salivary protein complexes by mass spectrometry. Effect of salivary protein profile, tannin concentration, and time stability.

PubMed

Perez-Gregorio, Maria Rosa; Mateus, Nuno; De Freitas, Victor

2014-10-15

Several factors could influence the tannin-protein interaction such as the human salivary protein profile, the tannin tested, and the tannin/protein ratio. The goal of this study aims to study the effect of different salivas (A, B, and C) and different tannin concentrations (0.5 and 1 mg/mL) on the interaction process as well as the complex's stability over time. This study is focused on the identification of new procyanidin B3-human salivary protein complexes. Thus, 48 major B3-human salivary protein aggregates were identified regardless of the saliva and tannin concentration tested. A higher number of aggregates was found at lower tannin concentration. Moreover, the number of protein moieties involved in the aggregation process was higher when the tannin concentration was also higher. The selectivity of the different groups of proteins to bind tannin was also confirmed. It was also verified that the B3-human salivary protein complexes formed evolved over time.

Pullout resistance of mechanically stabilized earth wall steel strip reinforcement in uniform aggregate : [technical summary].

DOT National Transportation Integrated Search

2015-11-01

A wide range of reinforcement-backfill combinations have been used in mechanically : stabilized earth (MSE) walls. Steel strips are one type of reinforcement used to stabilize : aggregate backfill through anchorage. In the current MSE wall design, pu...

Study of production and pyrolysis characteristics of sweet orange flavor-β-cyclodextrin inclusion complex.

PubMed

Zhu, Guangyong; Xiao, Zuobing; Zhou, Rujun; Zhu, Yalun

2014-05-25

Flavor plays an important role and has been widely used in foods. Encapsulation can prevent the loss of volatile aromatic ingredients, provide protection and enhance the stability of the flavor. Kinetic and thermodynamic parameters are helpful in understanding the mechanism of molecular recognition between hosts and guests. This work focused on the study of production of a sweet orange flavor-β-cyclodextrin (CD) inclusion complex, and investigated the combination of flavor and β-CD by thermogravimetric analysis. Pyrolysis characteristics, kinetic and thermodynamic parameters of the flavor-β-CD inclusion complex were determined. The results showed that the flavor-β-CD inclusion complexes can form large aggregates in water. During thermal degradation of blank β-CD and flavor-β-CD inclusion complex, three main stages can be distinguished. The thermogravimetric (TG) curve of blank β-CD shows a leveling-off from room temperature to 250°C, while the TG curve of flavor-β-CD inclusion complex is downward sloping in this temperature range. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coordination-Directed Stacking and Aggregation-Induced Emission Enhancement of the Zn(II) Schiff Base Complex.

PubMed

Wang, Dan; Li, Shu-Mu; Zheng, Jian-Quan; Kong, Duan-Yang; Zheng, Xiang-Jun; Fang, De-Cai; Jin, Lin-Pei

2017-01-17

2-(Trityliminomethyl)-quinolin-8-ol (HL) and its Zn(II) complex were synthesized and characterized by single-crystal X-ray diffraction. HL is an unsymmetrical molecule and coordinated with Zn(II) ion to form ZnL 2 in the antiparallel-mode arrangement via Zn-O (hydroxyl group) and Zn-N (quinoline ring) of HL. A high degree of ZnL 2 molecules ordering stacking is formed by the coordination bonds and intermolecular π-π interactions, in which head-to-tail arrangement (J-mode stacking) for L - is found. HL is nonfluorescent and ZnL 2 is weakly fluorescent in THF. The fluorescence emission of ZnL 2 enhances in THF/H 2 O as H 2 O% (volume %) is above 60% and aggregates particles with several hundred nanometers are formed, which is confirmed by DLS data and TEM images. The J-aggregates stacking for L - in ZnL 2 results in aggregation-induced emission enhancement (AIEE) for ZnL 2 in THF/H 2 O. Theoretical computations based on B3LYP/6-31G(d, p) and TD-B3LYP/6-31G(d, p) methods were carried out. ESIPT is the supposed mechanism for fluorescent silence of HL, and fluorescence emission of ZnL 2 is attributed to the restriction of ESIPT process. The oscillator strength of ZnL 2 increases from 0.017 for monomer to 0.032 for trimer. It indicates that a high degree of ZnL 2 molecules ordering stacking in THF/H 2 O is of benefit to fluorescence enhancement. HL is an ESIPT-coupled AIEE chemosensor for Zn(II) with high selectivity and sensitivity in aqueous medium. HL can efficiently detect intracellular Zn(II) ions because of ESIPT-coupled AIEE property of ZnL 2 in mixed solvent.

Data on optimum recycle aggregate content in production of new structural concrete.

PubMed

Paul, Suvash Chandra

2017-12-01

This data presented herein are the research summary of "mechanical behavior and durability performance of concrete containing recycled concrete aggregate" (Paul, 2011) [1]. The results reported in this article relate to an important parameter of optimum content of recycle concrete aggregate (RCA) in production of new concrete for both structural and non-structural applications. For the purpose of the research various types of physical, mechanical and durability tests are performed for concrete made with different percentages of RCA. Therefore, this data set can be a great help of the readers to understand the mechanism of RCA in relates to the concrete properties.

Aggregation and metal-complexation behaviour of THPP porphyrin in ethanol/water solutions as function of pH

NASA Astrophysics Data System (ADS)

Zannotti, Marco; Giovannetti, Rita; Minofar, Babak; Řeha, David; Plačková, Lydie; D'Amato, Chiara A.; Rommozzi, Elena; Dudko, Hanna V.; Kari, Nuerguli; Minicucci, Marco

2018-03-01

The effect of pH change on 5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine (THPP) with its aggregation as function of water-ethanol mixture was studied with UV-vis, fluorescence, Raman and computational analysis. In neutral pH, THPP was present as free-base and, increasing the water amount, aggregation occurred with the formation of H- and J-aggregates. The aggregation constant and the concentration of dimers were calculated, other information about the dimer aggregation were evaluated by computational study. In acidic pH, by the insertions of two hydrogens in the porphyrin rings, the porphyrin changed its geometry with a ring deformation confirmed by red-shifted spectrum and quenching in fluorescence; at this low pH, increasing the water amount, the acidic form (THPPH2)2 + resulted more stable due to a polar environment with stronger interaction by hydrogen bonding. In basic pH, reached by NH4OH, THPP porphyrin was able to react with alkali metals in order to form sitting-atop complex (M2THPP) confirmed by the typical absorption spectrum of metallo-porphyrin, Raman spectroscopy and by computational analysis.

Elasticity and critical bending moment of model colloidal aggregates.

PubMed

Pantina, John P; Furst, Eric M

2005-04-08

The bending mechanics of singly bonded colloidal aggregates are measured using laser tweezers. We find that the colloidal bonds are capable of supporting significant torques, providing a direct measurement of the tangential interactions between particles. A critical bending moment marks the limit of linear bending elasticity, past which small-scale rearrangements occur. These mechanical properties underlie the rheology and dynamics of colloidal gels formed by diffusion-limited cluster aggregation, and give critical insight into the contact interactions between Brownian particles.

A molecular rotor based ratiometric sensor for basic amino acids

NASA Astrophysics Data System (ADS)

Pettiwala, Aafrin M.; Singh, Prabhat K.

2018-01-01

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples.

Cadmium and naphthalene-induced hyperglycemia in the fiddler crab, Uca pugilator: Differential modes of action on the neutroendocrine system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, P.S.; Katyayani, R.V.; Fingerman, M.

1996-03-01

Hyperglycemia is a typical response of aquatic organisms to heavy metals. In crustaceans, the medulla terminalis X-organ-sinus gland neuroendocrine complex in the eyestalk is the source of the crustacean hyperglycemic hormone (CHH). The role of CHH in pollutant-induced b1ood glucose changes has only recently begun to be studied. Reddy provided evidence that CHH mediates cadmium-induced hyperglycemia in the red swamp crayfish, Procambarus clarkii. In a study of another hormonally-regulated function, color changes, cadmium exposure resulted in pigment in the melanophores of the fiddler crab, Uca pugilator, becoming less dispersed than in unexposed crabs. Earlier studies showed that, like cadmium, bothmore » a PCB, Aroclor 1242, and naphthalene induced black pigment aggregation in Uca poor. In general, when crabs are exposed to a pollutant, hydrocarbon or cadmium, they aggregate the pigment in their melanophores, but apparently by different mechanisms. Hydrocarbons appear to inhibit release of black pigment-dispersing hormone (BDPH), whereas cadmium appears to inhibit its synthesis. These apparent different modes of action of cadmium and naphthalene on the color change mechanism led us to compare the impact of these pollutants on the hormonal regulation of blood glucose in Uca pugilator. The present study was performed to determine (1) whether cadmium and naphthalene induce hyperglycemia in Uca pugilator, (2) whether CH has a role, if naphthalene and cadmium do induce hyperglycemia, and (3) the effects, if any, of cadmium and naphthalene on CHH activity in the eyestalk neuroendocrine complex.« less

Improving reliability of aggregation, numerical simulation and analysis of complex systems by empirical data

NASA Astrophysics Data System (ADS)

Dobronets, Boris S.; Popova, Olga A.

2018-05-01

The paper considers a new approach of regression modeling that uses aggregated data presented in the form of density functions. Approaches to Improving the reliability of aggregation of empirical data are considered: improving accuracy and estimating errors. We discuss the procedures of data aggregation as a preprocessing stage for subsequent to regression modeling. An important feature of study is demonstration of the way how represent the aggregated data. It is proposed to use piecewise polynomial models, including spline aggregate functions. We show that the proposed approach to data aggregation can be interpreted as the frequency distribution. To study its properties density function concept is used. Various types of mathematical models of data aggregation are discussed. For the construction of regression models, it is proposed to use data representation procedures based on piecewise polynomial models. New approaches to modeling functional dependencies based on spline aggregations are proposed.

Competitive aggregation dynamics using phase wave signals.

PubMed

Sakaguchi, Hidetsugu; Maeyama, Satomi

2014-10-21

Coupled equations of the phase equation and the equation of cell concentration n are proposed for competitive aggregation dynamics of slime mold in two dimensions. Phase waves are used as tactic signals of aggregation in this model. Several aggregation clusters are formed initially, and target patterns appear around the localized aggregation clusters. Owing to the competition among target patterns, the number of the localized aggregation clusters decreases, and finally one dominant localized pattern survives. If the phase equation is replaced with the complex Ginzburg-Landau equation, several spiral patterns appear, and n is localized near the center of the spiral patterns. After the competition among spiral patterns, one dominant spiral survives. Copyright © 2014 Elsevier Ltd. All rights reserved.

An Investigation of Aggregation in Synergistic Solvent Extraction Systems

NASA Astrophysics Data System (ADS)

Jackson, Andy Steven

With an increasing focus on anthropogenic climate change, nuclear reactors present an attractive option for base load power generation with regard to air pollution and carbon emissions, especially when compared with traditional fossil fuel based options. However, used nuclear fuel (UNF) is highly radiotoxic and contains minor actinides (americium and curium) which remain more radiotoxic than natural uranium ore for hundreds of thousands of years, presenting a challenge for long-term storage . Advanced nuclear fuel recycling can reduce this required storage time to thousands of years by removing the highly radiotoxic minor actinides. Many advanced separation schemes have been proposed to achieve this separation but none have been implemented to date. A key feature among many proposed schemes is the use of more than one extraction reagent in a single extraction phase, which can lead to the phenomenon known as "synergism" in which the extraction efficiency for a combination of the reagents is greater than that of the individual extractants alone. This feature is not well understood for many systems and a comprehensive picture of the mechanism behind synergism does not exist. There are several proposed mechanisms for synergism though none have been used to model multiple extraction systems. This work examines several proposed advanced extractant combinations which exhibit synergism: 2-bromodecanoic acid (BDA) with 2,2':6',2"-terpyridine (TERPY), tri-n-butylphosphine oxide (TPBO) with 2-thenoyltrifluoro acetone (HTTA), and dinonylnaphthalene sulfonic acid (HDNNS) with 5,8-diethyl-7-hydroxy-dodecan-6-oxime (LIX). We examine two proposed synergistic mechanisms involving and attempt to verify the ability of these mechanisms to predict the extraction behavior of the chosen systems. These are a reverse micellar catalyzed extraction model and a mixed complex formation model. Neither was able to effectively predict the synergistic behavior of the systems. We further examine these systems for the presence of large reverse micellar aggregates and thermodynamic signatures of aggregation. Behaviors differed widely from system to system, suggesting the possibility of more than one mechanism being responsible for similar observed extraction trends.

Intermolecular interactions and aggregation of fac-tris(2-phenylpyridinato-C2,N)iridium(III) in nonpolar solvents.

PubMed

Takayasu, Satoshi; Suzuki, Takayoshi; Shinozaki, Kazuteru

2013-08-15

The intermolecular interaction and aggregation of the neutral complex fac-tris(2-phenylpyridinato-C(2),N)iridium(III) (fac-Ir(ppy)3) in solution was investigated. Intermolecular interactions were found to effectively decrease the luminescence lifetime via self-quenching with increasing fac-Ir(ppy)3 concentrations. A Stern-Volmer plot for quenching in acetonitrile was linear, due to bimolecular self-quenching, but curved in toluene as the result of excimer formation. (1)H NMR spectra demonstrated a monomer-aggregate equilibrium which resulted in spectral shifts depending on solvent polarity. X-ray crystallography provided structural information concerning the aggregate, which is based on a tetramer consisting of two Δ-fac-Ir(ppy)3-Λ-fac-Ir(ppy)3 pairs. Offset π-π stacking of ppy ligands and electrostatic dipole-dipole interactions between complex molecules play an important role in the formation of these molecular pairs.

A Robust Damage Reporting Strategy for Polymeric Materials Enabled by Aggregation Induced Emission

DTIC Science & Technology

2016-08-17

and Technology, ‡Department of Chemistry, ∥Department of Materials Science and Engineering, ⊥Department of Mechanical Science and Engineering, and...enabled by aggregation-induced emission (AIE). This simple, yet powerful system relies on a single active component, and the general mechanism ...delivers outstanding performance in a wide variety of materials with diverse chemical and mechanical properties. Small (micrometer) scale damage in

Sequestration of synaptic proteins by alpha-synuclein aggregates leading to neurotoxicity is inhibited by small peptide

PubMed Central

Choi, Mal-Gi; Kim, Mi Jin; Kim, Do-Geun; Yu, Ri; Jang, You-Na

2018-01-01

α-Synuclein (α-syn) is a major component of Lewy bodies found in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Under the pathological conditions, α-syn tends to generate a diverse form of aggregates showing toxicity to neuronal cells and able to transmit across cells. However, mechanisms by which α-syn aggregates affect cytotoxicity in neurons have not been fully elucidated. Here we report that α-syn aggregates preferentially sequester specific synaptic proteins such as vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 (SNAP25) through direct binding which is resistant to SDS. The sequestration effect of α-syn aggregates was shown in a cell-free system, cultured primary neurons, and PD mouse model. Furthermore, we identified a specific blocking peptide derived from VAMP2 which partially inhibited the sequestration by α-syn aggregates and contributed to reduced neurotoxicity. These results provide a mechanism of neurotoxicity mediated by α-syn aggregates and suggest that the blocking peptide interfering with the pathological role of α-syn aggregates could be useful for designing a potential therapeutic drug for the treatment of PD. PMID:29608598

A probabilistic mechanical model for prediction of aggregates’ size distribution effect on concrete compressive strength

NASA Astrophysics Data System (ADS)

Miled, Karim; Limam, Oualid; Sab, Karam

2012-06-01

To predict aggregates' size distribution effect on the concrete compressive strength, a probabilistic mechanical model is proposed. Within this model, a Voronoi tessellation of a set of non-overlapping and rigid spherical aggregates is used to describe the concrete microstructure. Moreover, aggregates' diameters are defined as statistical variables and their size distribution function is identified to the experimental sieve curve. Then, an inter-aggregate failure criterion is proposed to describe the compressive-shear crushing of the hardened cement paste when concrete is subjected to uniaxial compression. Using a homogenization approach based on statistical homogenization and on geometrical simplifications, an analytical formula predicting the concrete compressive strength is obtained. This formula highlights the effects of cement paste strength and aggregates' size distribution and volume fraction on the concrete compressive strength. According to the proposed model, increasing the concrete strength for the same cement paste and the same aggregates' volume fraction is obtained by decreasing both aggregates' maximum size and the percentage of coarse aggregates. Finally, the validity of the model has been discussed through a comparison with experimental results (15 concrete compressive strengths ranging between 46 and 106 MPa) taken from literature and showing a good agreement with the model predictions.

Physical and mechanical properties of mortars containing PET and PC waste aggregates.

PubMed

Hannawi, Kinda; Kamali-Bernard, Siham; Prince, William

2010-11-01

Non-biodegradable plastic aggregates made of polycarbonate (PC) and polyethylene terephthalate (PET) waste are used as partial replacement of natural aggregates in mortar. Various volume fractions of sand 3%, 10%, 20% and 50% are replaced by the same volume of plastic. This paper investigates the physical and mechanical properties of the obtained composites. The main results of this study show the feasibility of the reuse of PC and PET waste aggregates materials as partial volume substitutes for natural aggregates in cementitious materials. Despite of some drawbacks like a decrease in compressive strength, the use of PC and PET waste aggregates presents various advantages. A reduction of the specific weight of the cementitious materials and a significant improvement of their post-peak flexural behaviour are observed. The calculated flexural toughness factors increase significantly with increasing volume fraction of PET and PC-aggregates. Thus, addition of PC and PET plastic aggregates in cementitious materials seems to give good energy absorbing materials which is very interesting for several civil engineering applications like structures subjected to dynamic or impact efforts. The present study has shown quite encouraging results and opened new way for the recycling of PC waste aggregate in cement and concrete composites. Copyright © 2010 Elsevier Ltd. All rights reserved.

Biointerface dynamics--Multi scale modeling considerations.

PubMed

Pajic-Lijakovic, Ivana; Levic, Steva; Nedovic, Viktor; Bugarski, Branko

2015-08-01

Irreversible nature of matrix structural changes around the immobilized cell aggregates caused by cell expansion is considered within the Ca-alginate microbeads. It is related to various effects: (1) cell-bulk surface effects (cell-polymer mechanical interactions) and cell surface-polymer surface effects (cell-polymer electrostatic interactions) at the bio-interface, (2) polymer-bulk volume effects (polymer-polymer mechanical and electrostatic interactions) within the perturbed boundary layers around the cell aggregates, (3) cumulative surface and volume effects within the parts of the microbead, and (4) macroscopic effects within the microbead as a whole based on multi scale modeling approaches. All modeling levels are discussed at two time scales i.e. long time scale (cell growth time) and short time scale (cell rearrangement time). Matrix structural changes results in the resistance stress generation which have the feedback impact on: (1) single and collective cell migrations, (2) cell deformation and orientation, (3) decrease of cell-to-cell separation distances, and (4) cell growth. Herein, an attempt is made to discuss and connect various multi scale modeling approaches on a range of time and space scales which have been proposed in the literature in order to shed further light to this complex course-consequence phenomenon which induces the anomalous nature of energy dissipation during the structural changes of cell aggregates and matrix quantified by the damping coefficients (the orders of the fractional derivatives). Deeper insight into the matrix partial disintegration within the boundary layers is useful for understanding and minimizing the polymer matrix resistance stress generation within the interface and on that base optimizing cell growth. Copyright © 2015 Elsevier B.V. All rights reserved.

Study on preparation and formation mechanism of n-alkanol/water emulsion using alpha-cyclodextrin.

PubMed

Hashizaki, Kaname; Kageyama, Takashi; Inoue, Motoki; Taguchi, Hiroyuki; Ueda, Haruhisa; Saito, Yoshihiro

2007-11-01

Surfactants are usually used for the preparation of emulsions; however, some have an adverse effect on the human body such as skin irritation, hemolysis, and protein denaturation, etc. In this study, we examined the preparation and formation mechanism of n-alkanol/water emulsions using alpha-cyclodextrin (alpha-CD) as an emulsifier. Emulsions were prepared by mixing oil and water phases for 4 min at 2500 rpm using a vortex mixer. The mechanism of emulsification was investigated with some physico-chemical techniques. From phase diagrams of n-alkanol/alpha-CD/water systems, the emulsion phase extended as the chain length of n-alkanols and the amount of alpha-CD added increased. Furthermore, the emulsion was not formed in the region where the n-alkanol/alpha-CD complex didn't precipitate; however, the emulsion was formed in the region where the complex precipitated. In addition, it was clear that the emulsions have a yield stress value and correspond to the Maxwell model from rheological measurement. Our experiments clearly showed that the stable emulsions are formed because the precipitated complexes form a dense film at the oil-water interface and prevent aggregation among dispersed phases. Furthermore, it is suggested that the creation of a three-dimensional network structure formed by precipitated complexes in the continuous phase contributes to the stabilization of the emulsion. Thus, we concluded that the n-alkanol/water emulsions using alpha-cyclodextrin were a kind of the Pickering emulsion.

Proteins containing expanded polyglutamine tracts and neurodegenerative disease

PubMed Central

Adegbuyiro, Adewale; Sedighi, Faezeh; Pilkington, Albert W.; Groover, Sharon; Legleiter, Justin

2017-01-01

Several hereditary neurological and neuromuscular diseases are caused by an abnormal expansion of trinucleotide repeats. To date, there have been ten of these trinucleotide repeat disorders associated with an expansion of the codon CAG encoding glutamine (Q). For these polyglutamine (polyQ) diseases, there is a critical threshold length of the CAG repeat required for disease, and further expansion beyond this threshold is correlated with age of onset and symptom severity. PolyQ expansion in the translated proteins promotes their self-assembly into a variety of oligomeric and fibrillar aggregate species that accumulate into the hallmark proteinaceous inclusion bodies associated with each disease. Here, we review aggregation mechanisms of proteins with expanded polyQ-tracts, structural consequences of expanded polyQ ranging from monomers to fibrillar aggregates, the impact of protein context and post translational modifications on aggregation, and a potential role for lipids membranes in aggregation. As the pathogenic mechanisms that underlie these disorders are often classified as either a gain of toxic function or loss of normal protein function, some toxic mechanisms associated with mutant polyQ tracts will also be discussed. PMID:28170216

Dynamic Imaging by Fluorescence Correlation Spectroscopy Identifies Diverse Populations of Polyglutamine Oligomers Formed in Vivo*

PubMed Central

Beam, Monica; Silva, M. Catarina; Morimoto, Richard I.

2012-01-01

Protein misfolding and aggregation are exacerbated by aging and diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer. In the cellular environment, aggregates can exist as discrete entities, or heterogeneous complexes of diverse solubility and conformational state. In this study, we have examined the in vivo dynamics of aggregation using imaging methods including fluorescence microscopy, fluorescence recovery after photobleaching (FRAP), and fluorescence correlation spectroscopy (FCS), to monitor the diverse biophysical states of expanded polyglutamine (polyQ) proteins expressed in Caenorhabditis elegans. We show that monomers, oligomers and aggregates co-exist at different concentrations in young and aged animals expressing different polyQ-lengths. During aging, when aggregation and toxicity are exacerbated, FCS-based burst analysis and purified single molecule FCS detected a populational shift toward an increase in the frequency of brighter and larger oligomeric species. Regardless of age or polyQ-length, oligomers were maintained in a heterogeneous distribution that spans multiple orders of magnitude in brightness. We employed genetic suppressors that prevent polyQ aggregation and observed a reduction in visible immobile species with the persistence of heterogeneous oligomers, yet our analysis did not detect the appearance of any discrete oligomeric states associated with toxicity. These studies reveal that the reversible transition from monomers to immobile aggregates is not represented by discrete oligomeric states, but rather suggests that the process of aggregation involves a more complex pattern of molecular interactions of diverse intermediate species that can appear in vivo and contribute to aggregate formation and toxicity. PMID:22669943

Quantifying Aggregation Dynamics during Myxococcus xanthus Development▿†

PubMed Central

Zhang, Haiyang; Angus, Stuart; Tran, Michael; Xie, Chunyan; Igoshin, Oleg A.; Welch, Roy D.

2011-01-01

Under starvation conditions, a swarm of Myxococcus xanthus cells will undergo development, a multicellular process culminating in the formation of many aggregates called fruiting bodies, each of which contains up to 100,000 spores. The mechanics of symmetry breaking and the self-organization of cells into fruiting bodies is an active area of research. Here we use microcinematography and automated image processing to quantify several transient features of developmental dynamics. An analysis of experimental data indicates that aggregation reaches its steady state in a highly nonmonotonic fashion. The number of aggregates rapidly peaks at a value 2- to 3-fold higher than the final value and then decreases before reaching a steady state. The time dependence of aggregate size is also nonmonotonic, but to a lesser extent: average aggregate size increases from the onset of aggregation to between 10 and 15 h and then gradually decreases thereafter. During this process, the distribution of aggregates transitions from a nearly random state early in development to a more ordered state later in development. A comparison of experimental results to a mathematical model based on the traffic jam hypothesis indicates that the model fails to reproduce these dynamic features of aggregation, even though it accurately describes its final outcome. The dynamic features of M. xanthus aggregation uncovered in this study impose severe constraints on its underlying mechanisms. PMID:21784940

Mechanisms of fibrinogen-acebutolol interactions: Insights from DSC, CD and LS.

PubMed

Hassan, Natalia; Ruso, Juan M; Somasundaran, P

2011-02-01

The complex formed due to the interaction of the amphiphilic betablocker acebutolol with fibrinogen in a buffer solution (50mN glycine, pH of 8.5) has been investigated using a multipronged physicochemical approach. Differential scanning calorimetry measurements of the complexes have shown no reversibility of thermal denaturation as indicated by the three observed peaks and the opposite role that acebutolol plays in the folding different domains of the fibrinogen molecule and the stability of such domains. While circular dichroism measurements have revealed that interaction of acebutolol with fibrinogen affects the protein secondary structure to a different extent depending on the temperature and drug concentration, dynamic light scattering analysis showed evidence for protein aggregation mainly to tetramers and dimers. Copyright © 2010 Elsevier B.V. All rights reserved.

DNA sensors and aptasensors based on the hemin/G-quadruplex-controlled aggregation of Au NPs in the presence of L-cysteine.

PubMed

Niazov-Elkan, Angelica; Golub, Eyal; Sharon, Etery; Balogh, Dora; Willner, Itamar

2014-07-23

L-cysteine induces the aggregation of Au nanoparticles (NPs), resulting in a color transition from red to blue due to interparticle plasmonic coupling in the aggregated structure. The hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme catalyzes the aerobic oxidation of L-cysteine to cystine, a process that inhibits the aggregation of the NPs. The degree of inhibition of the aggregation process is controlled by the concentration of the DNAzyme in the system. These functions are implemented to develop sensing platforms for the detection of a target DNA, for the analysis of aptamer-substrate complexes, and for the analysis of L-cysteine in human urine samples. A hairpin DNA structure that includes a recognition site for the DNA analyte and a caged G-quadruplex sequence, is opened in the presence of the target DNA. The resulting self-assembled hemin/G-quadruplex acts as catalyst that controls the aggregation of the Au NPs. Also, the thrombin-binding aptamer folds into a G-quadruplex nanostructure upon binding to thrombin. The association of hemin to the resulting G-quadruplex aptamer-thrombin complex leads to a catalytic label that controls the L-cysteine-mediated aggregation of the Au NPs. The hemin/G-qaudruplex-controlled aggregation of Au NPs process is further implemented for visual and spectroscopic detection of L-cysteine concentration in urine samples. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrostatic interactions lead to the formation of asymmetric collagen-phosphophoryn aggregates.

PubMed

Dahl, Thomas; Veis, Arthur

2003-01-01

In bone and dentin the formation and mineralization of the extra cellular matrix structure is a complex process highly dependent on intermolecular interactions. In dentin, the phosphophoryns (PP) and type I collagen (COL1) are the major constituents implicated in mineralization. Thus, as a first step in understanding the tissue organization, we have initiated a study of their interaction as a function of pH, ionic strength, and relative concentrations or mixing ratios. Complex formation has been analyzed by dynamic light scattering to detect aggregate formation and by rotary shadowing electron microscopy (EM) to determine aggregate shape. The EM data showed that at the pH values studied, the PP-COL1 interaction leads to the formation of large fibrillar aggregates in which the PP are present along the fibril surfaces. The quantitative phase distribution data showed a 1/1 molar equivalence at the maximum aggregation point, not at electrostatic PP-COL1 equivalence. As the ionic strength was raised, the PP-COL1 aggregates became smaller but the binding and asymmetric fibrillar aggregation persisted. In EM, the PP appear as dense spheres. Along the surfaces of the collagen aggregates, the PP are larger and more open or extended, suggesting that COL1-bound PP may undergo a conformational change, opening up so that a single PP molecule might interact with and electrostatically link several COL1 molecules. This might have important implications for dentin structure, stability, and mineralization.

Effects of surfactants on lipase structure, activity, and inhibition.

PubMed

Delorme, Vincent; Dhouib, Rabeb; Canaan, Stéphane; Fotiadu, Frédéric; Carrière, Frédéric; Cavalier, Jean-François

2011-08-01

Lipase inhibitors are the main anti-obesity drugs prescribed these days, but the complexity of their mechanism of action is making it difficult to develop new molecules for this purpose. The efficacy of these drugs is known to depend closely on the physico-chemistry of the lipid-water interfaces involved and on the unconventional behavior of the lipases which are their target enzymes. The lipolysis reaction which occurs at an oil-water interface involves complex equilibria between adsorption-desorption processes, conformational changes and catalytic mechanisms. In this context, surfactants can induce significant changes in the partitioning of the enzyme and the inhibitor between the water phase and lipid-water interfaces. Surfactants can be found at the oil-water interface where they compete with lipases for adsorption, but also in solution in the form of micellar aggregates and monomers that may interact with hydrophobic parts of lipases in solution. These various interactions, combined with the emulsification and dispersion of insoluble substrates and inhibitors, can either promote or decrease the activity and the inhibition of lipases. Here, we review some examples of the various effects of surfactants on lipase structure, activity and inhibition, which show how complex the various equilibria involved in the lipolysis reaction tend to be.

Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

PubMed Central

Xu, Zhi-Xue; Zhang, Qiang; Ma, Gong-Li; Chen, Cong-Heng; He, Yan-Ming; Xu, Li-Hui; Zhang, Yuan; Zhou, Guang-Rong; Li, Zhen-Hua

2016-01-01

The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes. PMID:28074190

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.

PubMed

Seidel, K; Vinet, J; Dunnen, W F A den; Brunt, E R; Meister, M; Boncoraglio, A; Zijlstra, M P; Boddeke, H W G M; Rüb, U; Kampinga, H H; Carra, S

2012-02-01

HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate-prone protein-mediated toxicity. Here we analysed HSPB8-BAG3 expression levels in post-mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post-mortem brain tissues, respectively. In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8-BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates. We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Energy transfer dynamics in trimers and aggregates of light-harvesting complex II probed by 2D electronic spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enriquez, Miriam M.; Zhang, Cheng; Tan, Howe-Siang, E-mail: howesiang@ntu.edu.sg

2015-06-07

The pathways and dynamics of excitation energy transfer between the chlorophyll (Chl) domains in solubilized trimeric and aggregated light-harvesting complex II (LHCII) are examined using two-dimensional electronic spectroscopy (2DES). The LHCII trimers and aggregates exhibit the unquenched and quenched excitonic states of Chl a, respectively. 2DES allows direct correlation of excitation and emission energies of coupled states over population time delays, hence enabling mapping of the energy flow between Chls. By the excitation of the entire Chl b Q{sub y} band, energy transfer from Chl b to Chl a states is monitored in the LHCII trimers and aggregates. Global analysismore » of the two-dimensional (2D) spectra reveals that energy transfer from Chl b to Chl a occurs on fast and slow time scales of 240–270 fs and 2.8 ps for both forms of LHCII. 2D decay-associated spectra resulting from the global analysis identify the correlation between Chl states involved in the energy transfer and decay at a given lifetime. The contribution of singlet–singlet annihilation on the kinetics of Chl energy transfer and decay is also modelled and discussed. The results show a marked change in the energy transfer kinetics in the time range of a few picoseconds. Owing to slow energy equilibration processes, long-lived intermediate Chl a states are present in solubilized trimers, while in aggregates, the population decay of these excited states is significantly accelerated, suggesting that, overall, the energy transfer within the LHCII complexes is faster in the aggregated state.« less

Hail formation triggers rapid ash aggregation in volcanic plumes

USGS Publications Warehouse

Van Eaton, Alexa R.; Mastin, Larry G.; Herzog, M.; Schwaiger, Hans F.; Schneider, David J.; Wallace, Kristi; Clarke, Amanda B

2015-01-01

During explosive eruptions, airborne particles collide and stick together, accelerating the fallout of volcanic ash and climate-forcing aerosols. This aggregation process remains a major source of uncertainty both in ash dispersal forecasting and interpretation of eruptions from the geological record. Here we illuminate the mechanisms and timescales of particle aggregation from a well-characterized ‘wet’ eruption. The 2009 eruption of Redoubt Volcano in Alaska incorporated water from the surface (in this case, a glacier), which is a common occurrence during explosive volcanism worldwide. Observations from C-band weather radar, fall deposits, and numerical modeling demonstrate that volcanic hail formed rapidly in the eruption plume, leading to mixed-phase aggregation of ~95% of the fine ash and stripping much of the cloud out of the atmosphere within 30 minutes. Based on these findings, we propose a mechanism of hail-like aggregation that contributes to the anomalously rapid fallout of fine ash and the occurrence of concentrically-layered aggregates in volcanic deposits.

Two-Step Amyloid Aggregation: Sequential Lag Phase Intermediates

NASA Astrophysics Data System (ADS)

Castello, Fabio; Paredes, Jose M.; Ruedas-Rama, Maria J.; Martin, Miguel; Roldan, Mar; Casares, Salvador; Orte, Angel

2017-01-01

The self-assembly of proteins into fibrillar structures called amyloid fibrils underlies the onset and symptoms of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. However, the molecular basis and mechanism of amyloid aggregation are not completely understood. For many amyloidogenic proteins, certain oligomeric intermediates that form in the early aggregation phase appear to be the principal cause of cellular toxicity. Recent computational studies have suggested the importance of nonspecific interactions for the initiation of the oligomerization process prior to the structural conversion steps and template seeding, particularly at low protein concentrations. Here, using advanced single-molecule fluorescence spectroscopy and imaging of a model SH3 domain, we obtained direct evidence that nonspecific aggregates are required in a two-step nucleation mechanism of amyloid aggregation. We identified three different oligomeric types according to their sizes and compactness and performed a full mechanistic study that revealed a mandatory rate-limiting conformational conversion step. We also identified the most cytotoxic species, which may be possible targets for inhibiting and preventing amyloid aggregation.

Hail formation triggers rapid ash aggregation in volcanic plumes.

PubMed

Van Eaton, Alexa R; Mastin, Larry G; Herzog, Michael; Schwaiger, Hans F; Schneider, David J; Wallace, Kristi L; Clarke, Amanda B

2015-08-03

During explosive eruptions, airborne particles collide and stick together, accelerating the fallout of volcanic ash and climate-forcing aerosols. This aggregation process remains a major source of uncertainty both in ash dispersal forecasting and interpretation of eruptions from the geological record. Here we illuminate the mechanisms and timescales of particle aggregation from a well-characterized 'wet' eruption. The 2009 eruption of Redoubt Volcano, Alaska, incorporated water from the surface (in this case, a glacier), which is a common occurrence during explosive volcanism worldwide. Observations from C-band weather radar, fall deposits and numerical modelling demonstrate that hail-forming processes in the eruption plume triggered aggregation of ∼95% of the fine ash and stripped much of the erupted mass out of the atmosphere within 30 min. Based on these findings, we propose a mechanism of hail-like ash aggregation that contributes to the anomalously rapid fallout of fine ash and occurrence of concentrically layered aggregates in volcanic deposits.

Hail formation triggers rapid ash aggregation in volcanic plumes

PubMed Central

Van Eaton, Alexa R.; Mastin, Larry G.; Herzog, Michael; Schwaiger, Hans F.; Schneider, David J.; Wallace, Kristi L.; Clarke, Amanda B.

2015-01-01

During explosive eruptions, airborne particles collide and stick together, accelerating the fallout of volcanic ash and climate-forcing aerosols. This aggregation process remains a major source of uncertainty both in ash dispersal forecasting and interpretation of eruptions from the geological record. Here we illuminate the mechanisms and timescales of particle aggregation from a well-characterized ‘wet' eruption. The 2009 eruption of Redoubt Volcano, Alaska, incorporated water from the surface (in this case, a glacier), which is a common occurrence during explosive volcanism worldwide. Observations from C-band weather radar, fall deposits and numerical modelling demonstrate that hail-forming processes in the eruption plume triggered aggregation of ∼95% of the fine ash and stripped much of the erupted mass out of the atmosphere within 30 min. Based on these findings, we propose a mechanism of hail-like ash aggregation that contributes to the anomalously rapid fallout of fine ash and occurrence of concentrically layered aggregates in volcanic deposits. PMID:26235052

Physical mechanisms for chemotactic pattern formation by bacteria.

PubMed Central

Brenner, M P; Levitov, L S; Budrene, E O

1998-01-01

This paper formulates a theory for chemotactic pattern formation by the bacteria Escherichia coli in the presence of excreted attractant. In a chemotactically neutral background, through chemoattractant signaling, the bacteria organize into swarm rings and aggregates. The analysis invokes only those physical processes that are both justifiable by known biochemistry and necessary and sufficient for swarm ring migration and aggregate formation. Swarm rings migrate in the absence of an external chemoattractant gradient. The ring motion is caused by the depletion of a substrate that is necessary to produce attractant. Several scaling laws are proposed and are demonstrated to be consistent with experimental data. Aggregate formation corresponds to finite time singularities in which the bacterial density diverges at a point. Instabilities of swarm rings leading to aggregate formation occur via a mechanism similar to aggregate formation itself: when the mass density of the swarm ring exceeds a threshold, the ring collapses cylindrically and then destabilizes into aggregates. This sequence of events is demonstrated both in the theoretical model and in the experiments. PMID:9545032

Impact load-induced micro-structural damage and micro-structure associated mechanical response of concrete made with different surface roughness and porosity aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erdem, Savas, E-mail: evxse1@nottingham.ac.uk; Dawson, Andrew Robert; Thom, Nicholas Howard

2012-02-15

The relationship between the nature of micro damage under impact loading and changes in mechanical behavior associated with different microstructures is studied for concretes made with two different coarse aggregates having significant differences mainly in roughness and porosity - sintered fly ash and uncrushed gravel. A range of techniques including X-ray diffraction, digital image analysis, mercury porosimetry, X-ray computed tomography, laser surface profilometry and scanning electron microscopy were used to characterize the aggregates and micro-structures. The concrete prepared with lightweight aggregates was stronger in compression than the gravel aggregate concrete due to enhanced hydration as a result of internal curing.more » In the lightweight concrete, it was deduced that an inhomogeneous micro-structure led to strain incompatibilities and consequent localized stress concentrations in the mix, leading to accelerated failure. The pore structure, compressibility, and surface texture of the aggregates are of paramount importance for the micro-cracking growth.« less

Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key

PubMed Central

Das, Utpal; Hariprasad, Gururao; Ethayathulla, Abdul S.; Manral, Pallavi; Das, Taposh K.; Pasha, Santosh; Mann, Anita; Ganguli, Munia; Verma, Amit K.; Bhat, Rajiv; Chandrayan, Sanjeev Kumar; Ahmed, Shubbir; Sharma, Sujata; Kaur, Punit; Singh, Tej P.; Srinivasan, Alagiri

2007-01-01

Background Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. Methodology We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Aβ1-42) peptide is modified. Changes in the hydrodynamic volume of Aβ1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Aβ1-42. Arginine increases the solubility of Aβ1-42 peptide in aqueous medium. It decreases the aggregation of Aβ1-42 as observed by atomic force microscopy. Conclusions Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation. PMID:18000547

Examination of molecular mechanism for the enhanced thermal stability of anthocyanins by metal cations and polysaccharides.

PubMed

Tachibana, Noriko; Kimura, Yukihiro; Ohno, Takashi

2014-01-15

Anthocyanins exhibit colour variation over wide pH range but the colour stability is relatively low at the physiological pH. To improve the stability of anthocyanins in neutral to weakly acidic pH region, effects of metal cations and polysaccharides on the colour stability of cyanidin-3-glucoside (C3G) were examined by ultraviolet-visible and resonance Raman spectroscopies. C3G was thermally stabilized by the addition of Fe(3+) but formed aggregation. However, further addition of anionic polysaccharides enhanced the thermal stability of C3G without aggregation. Similar stabilisation was confirmed for delphinidin-3-glucoside (D3G) but not for pelargonidin-3-glucoside. The stability of anthocyanins considerably varied depending on pHs and kinds of metal cations, polysaccharides and buffer molecules. The characteristic resonance Raman bands of C3G-Fe(3+) and D3G-Fe(3+) complexes were significantly affected by the addition of alginate, (18)O/(16)O-isotope substitution, and Fe(2+)/Fe(3+)-replacement. These results suggest that alginate associates with C3G through Fe(3+) to form a stable complex, which enhances the thermal stability of C3G. Copyright © 2013 Elsevier Ltd. All rights reserved.

Complex Behavior of Aqueous α-Cyclodextrin Solutions. Interfacial Morphologies Resulting from Bulk Aggregation.

PubMed

Hernandez-Pascacio, Jorge; Piñeiro, Ángel; Ruso, Juan M; Hassan, Natalia; Campbell, Richard A; Campos-Terán, José; Costas, Miguel

2016-07-05

The spontaneous aggregation of α-cyclodextrin (α-CD) molecules in the bulk aqueous solution and the interactions of the resulting aggregates at the liquid/air interface have been studied at 283 K using a battery of techniques: transmission electron microscopy, dynamic light scattering, dynamic surface tensiometry, Brewster angle microscopy, neutron reflectometry, and ellipsometry. We show that α-CD molecules spontaneously form aggregates in the bulk that grow in size with time. These aggregates adsorb to the liquid/air interface with their size in the bulk determining the adsorption rate. The material that reaches the interface coalesces laterally to form two-dimensional domains on the micrometer scale with a layer thickness on the nanometer scale. These processes are affected by the ages of both the bulk and the interface. The interfacial layer formed is not in fast dynamic equilibrium with the subphase as the resulting morphology is locked in a kinetically trapped state. These results reveal a surprising complexity of the parallel physical processes taking place in the bulk and at the interface of what might have seemed initially like a simple system.

Pseudocatalytic Antiaggregation Activity of Antibodies: Immunoglobulins can Influence α-Synuclein Aggregation at Substoichiometric Concentrations.

PubMed

Breydo, Leonid; Morgan, Dave; Uversky, Vladimir N

2016-04-01

Protein aggregation is involved in a variety of diseases. Alteration of the aggregation pathway, either to produce less toxic structures or to increase aggregate clearance, is a promising therapeutic route. Both active and passive immunization has been used for this purpose. However, the mechanism of action of antibodies on protein aggregates is not completely clear especially given poor ability of antibodies to cross blood-brain barrier. Here, we have shown that antibodies can interfere with protein aggregation at substoichiometric concentrations (as low as 1:1000 antibody to protein ratio). This is an indication that antibodies interact with aggregation intermediates in chaperone-like manner altering the aggregation pathways at very low antibody levels. This observation supports earlier suggestions that antibodies can inhibit aggregation by interaction with low abundance aggregation intermediates.

Ash aggregation enhanced by deposition and redistribution of salt on the surface of volcanic ash in eruption plumes.

PubMed

Mueller, Sebastian B; Ayris, Paul M; Wadsworth, Fabian B; Kueppers, Ulrich; Casas, Ana S; Delmelle, Pierre; Taddeucci, Jacopo; Jacob, Michael; Dingwell, Donald B

2017-03-31

Interactions with volcanic gases in eruption plumes produce soluble salt deposits on the surface of volcanic ash. While it has been postulated that saturation-driven precipitation of salts following the dissolution of ash surfaces by condensed acidic liquids is a primary mechanism of salt formation during an eruption, it is only recently that this mechanism has been subjected to detailed study. Here we spray water and HCl droplets into a suspension of salt-doped synthetic glass or volcanic ash particles, and produce aggregates. Deposition of acidic liquid droplets on ash particles promotes dissolution of existing salts and leaches cations from the underlying material surface. The flow of liquid, due to capillary forces, will be directed to particle-particle contact points where subsequent precipitation of salts will cement the aggregate. Our data suggest that volcanically-relevant loads of surface salts can be produced by acid condensation in eruptive settings. Several minor and trace elements mobilised by surface dissolution are biologically relevant; geographic areas with aggregation-mediated ash fallout could be "hotspots" for the post-deposition release of these elements. The role of liquids in re-distributing surface salts and cementing ash aggregates also offers further insight into the mechanisms which preserve well-structured aggregates in some ash deposits.

Ash aggregation enhanced by deposition and redistribution of salt on the surface of volcanic ash in eruption plumes

PubMed Central

Mueller, Sebastian B.; Ayris, Paul M.; Wadsworth, Fabian B.; Kueppers, Ulrich; Casas, Ana S.; Delmelle, Pierre; Taddeucci, Jacopo; Jacob, Michael; Dingwell, Donald B.

2017-01-01

Interactions with volcanic gases in eruption plumes produce soluble salt deposits on the surface of volcanic ash. While it has been postulated that saturation-driven precipitation of salts following the dissolution of ash surfaces by condensed acidic liquids is a primary mechanism of salt formation during an eruption, it is only recently that this mechanism has been subjected to detailed study. Here we spray water and HCl droplets into a suspension of salt-doped synthetic glass or volcanic ash particles, and produce aggregates. Deposition of acidic liquid droplets on ash particles promotes dissolution of existing salts and leaches cations from the underlying material surface. The flow of liquid, due to capillary forces, will be directed to particle-particle contact points where subsequent precipitation of salts will cement the aggregate. Our data suggest that volcanically-relevant loads of surface salts can be produced by acid condensation in eruptive settings. Several minor and trace elements mobilised by surface dissolution are biologically relevant; geographic areas with aggregation-mediated ash fallout could be “hotspots” for the post-deposition release of these elements. The role of liquids in re-distributing surface salts and cementing ash aggregates also offers further insight into the mechanisms which preserve well-structured aggregates in some ash deposits. PMID:28361966

Corrosion Behavior of Steel Reinforcement in Concrete with Recycled Aggregates, Fly Ash and Spent Cracking Catalyst.

PubMed

Gurdián, Hebé; García-Alcocel, Eva; Baeza-Brotons, Francisco; Garcés, Pedro; Zornoza, Emilio

2014-04-21

The main strategy to reduce the environmental impact of the concrete industry is to reuse the waste materials. This research has considered the combination of cement replacement by industrial by-products, and natural coarse aggregate substitution by recycled aggregate. The aim is to evaluate the behavior of concretes with a reduced impact on the environment by replacing a 50% of cement by industrial by-products (15% of spent fluid catalytic cracking catalyst and 35% of fly ash) and a 100% of natural coarse aggregate by recycled aggregate. The concretes prepared according to these considerations have been tested in terms of mechanical strengths and the protection offered against steel reinforcement corrosion under carbonation attack and chloride-contaminated environments. The proposed concrete combinations reduced the mechanical performance of concretes in terms of elastic modulus, compressive strength, and flexural strength. In addition, an increase in open porosity due to the presence of recycled aggregate was observed, which is coherent with the changes observed in mechanical tests. Regarding corrosion tests, no significant differences were observed in the case of the resistance of these types of concretes under a natural chloride attack. In the case of carbonation attack, although all concretes did not stand the highly aggressive conditions, those concretes with cement replacement behaved worse than Portland cement concretes.

Soot Superaggregates from Flaming Wildfires and Their Direct Radiative Forcing

NASA Technical Reports Server (NTRS)

Chakrabarty, Rajan K.; Beres, Nicholas D.; Moosmuller,Hans; China, Swarup; Mazzoleni, Claudio; Dubey, Manvendra K.; Liu, Li; Mishchenko, Michael I.

2014-01-01

Wildfires contribute significantly to global soot emissions, yet their aerosol formation mechanisms and resulting particle properties are poorly understood and parameterized in climate models. The conventional view holds that soot is formed via the cluster-dilute aggregation mechanism in wildfires and emitted as aggregates with fractal dimension D(sub f) approximately equals 1.8 mobility diameter D(sub m) (is) less than or equal to 1 micron, and aerodynamic diameter D(sub a) (is) less than or equal to 300 nm. Here we report the ubiquitous presence of soot superaggregates (SAs) in the outflow from a major wildfire in India. SAs are porous, low-density aggregates of cluster-dilute aggregates with characteristic D(sub f) approximately equals 2.6,D(sub m) (is) greater than 1 micron, and D(sub a) is less than or equal to 300 nm that form via the cluster-dense aggregation mechanism.We present additional observations of soot SAs in wildfire smoke-laden air masses over Northern California, New Mexico, and Mexico City. We estimate that SAs contribute, per unit optical depth, up to 35% less atmospheric warming than freshly-emitted (D(sub f) approximately equals 1.8) aggregates, and approximately equals 90% more warming than the volume-equivalent spherical soot particles simulated in climate models.

Failure of protein quality control in amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Durham, Heather D

2006-01-01

The protein chaperoning and ubiquitin-proteasome systems perform many homeostatic functions within cells involving protein folding, transport and degradation. Of paramount importance is ridding cells of mutant or post-translationally modified proteins that otherwise tend to aggregate into insoluble complexes and form inclusions. Such inclusions are characteristic of many neurodegenerative diseases and implicate protein misfolding and aggregation as common aspects of pathogenesis. In the most common familial form of ALS, mutations in SOD1 promote misfolding of the protein and target it for degradation by proteasomes. Although proteasomes can degrade the mutant proteins efficiently, altered solubility and aggregation of mutant SOD1 are features of the disease and occur most prominently in the most vulnerable cells and tissues. Indeed, lumbar spinal cord of mutant SOD1 transgenic mice show early reduction in their capacity for protein chaperoning and proteasome-mediated hydrolysis of substrates, and motor neurons are particularly vulnerable to aggregation of mutant SOD1. A high threshold for upregulating key pathways in response to the stress of added substrate load may contribute to this vulnerability. The broad spectrum neuroprotective capability and efficacy of some chaperone-based therapies in preclinical models makes these pathways attractive as targets for therapy in ALS, as well as other neurodegenerative diseases. A better understanding of the mechanisms governing the regulation of protein chaperones and UPS components would facilitate development of treatments that upregulate these pathways in a coordinated manner in neural tissue without long term toxicity.

Role of organic matter on aggregate stability and related mechanisms through organic amendments

NASA Astrophysics Data System (ADS)

Zaher, Hafida

2010-05-01

To date, only a few studies have tried to simultaneously compare the role of neutral and uronic sugars and lipids on soil structural stability. Moreover, evidence for the mechanisms involved has often been established following wetting of moist aggregates after various pre-treatments thus altering aggregate structure and resulting in manipulations on altered aggregates on which the rapid wetting process may not be involved anymore. To the best of our knowledge, the objective of this work was to study the role of neutral and uronic sugars and lipids in affecting key mechanisms (swelling rate, pressure evolution) involved in the stabilization of soil structure. A long-term incubation study (48-wk) was performed on a clay loam and a silty-clay loam amended with de-inking-secondary sludge mix at three rates (8, 16 and 24 Mg dry matter ha-1), primary-secondary sludge mix at one rate (18 Mg oven-dry ha-1) and composted de-inking sludge at one rate (24 Mg ha-1). Different structural stability indices (stability of moist and dry aggregates, the amount of dispersible clay and loss of soil material following sudden wetting) were measured on a regular basis during the incubation, along with CO2 evolved, neutral and uronic sugar, and lipid contents. During the course of the incubations, significant increases in all stability indices were measured for both soil types. In general, the improvements in stability were proportional to the amount of C added as organic amendments. These improvements were linked to a very intense phase of C mineralization and associated with increases in neutral and uronic sugars as well as lipid contents. The statistical relationships found between the different carbonaceous fractions and stability indices were all highly significant and indicated no clear superiority of one fraction over another. Paper sludge amendments also resulted in significant decreases in maximum internal pressure of aggregate and aggregate swelling following immersion in water, two mechanisms affecting structural stability. Overall, the results suggest that reduction in maximum internal pressure induced by organic amendments most likely resulted from increases in pore surface roughness and pore occlusion rather than by increase in surface wetting angles. This study also supports the view of a non specific action of the lipids, neutral and uronic sugars on aggregate stability to rapid wetting. Key words: soil aggregate stability, polysaccharides, lipids, mechanisms, organic matter

Effect of the LHCII pigment-protein complex aggregation on photovoltaic properties of sensitized TiO2 solar cells.

PubMed

Yang, Yiqun; Jankowiak, Ryszard; Lin, Chen; Pawlak, Krzysztof; Reus, Michael; Holzwarth, Alfred R; Li, Jun

2014-10-14

A modified dye-sensitized solar cell consisting of a thin TiO2 barrier layer sensitized with natural trimeric light-harvesting complex II (LHCII) from spinach was used as a biomimetic model to study the effects of LHCII aggregation on the photovoltaic properties. The aggregation of individual trimers induced molecular reorganization, which dramatically increased the photocurrent. The morphology of small- and large-size LHCII aggregates deposited on a surface was confirmed by atomic force microscopy. Enhanced LHCII immobilization was accomplished via electrostatic interaction with amine-functionalized photoanodes. The photocurrent responses of the assembled solar cells under illumination at three characteristic wavelength bands in the UV-Vis absorption spectra of LHCII solutions confirmed that a significant photocurrent was generated by LHCII photosensitizers. The enhanced photocurrent by large aggregated LHCII is shown to correlate with the quenching in the far-red fluorescence deriving from chlorophyll-chlorophyll charge transfer states that are effectively coupled with the TiO2 surface and thus inject electrons into the TiO2 conduction band. The large aggregated LHCII with more chlorophyll-chlorophyll charge transfer states is a much better sensitizer since it injects electrons more efficiently into the conduction band of TiO2 than the small aggregated LHCII mostly consisting of unquenched chlorophyll excited state. The assembled solar cells demonstrated remarkable stability in both aqueous buffer and acetonitrile electrolytes over 30 days.

Potential for direct interspecies electron transfer in methanogenic wastewater digester aggregates.

PubMed

Morita, Masahiko; Malvankar, Nikhil S; Franks, Ashley E; Summers, Zarath M; Giloteaux, Ludovic; Rotaru, Amelia E; Rotaru, Camelia; Lovley, Derek R

2011-01-01

Mechanisms for electron transfer within microbial aggregates derived from an upflow anaerobic sludge blanket reactor converting brewery waste to methane were investigated in order to better understand the function of methanogenic consortia. The aggregates were electrically conductive, with conductivities 3-fold higher than the conductivities previously reported for dual-species aggregates of Geobacter species in which the two species appeared to exchange electrons via interspecies electron transfer. The temperature dependence response of the aggregate conductance was characteristic of the organic metallic-like conductance previously described for the conductive pili of Geobacter sulfurreducens and was inconsistent with electron conduction through minerals. Studies in which aggregates were incubated with high concentrations of potential electron donors demonstrated that the aggregates had no significant capacity for conversion of hydrogen to methane. The aggregates converted formate to methane but at rates too low to account for the rates at which that the aggregates syntrophically metabolized ethanol, an important component of the reactor influent. Geobacter species comprised 25% of 16S rRNA gene sequences recovered from the aggregates, suggesting that Geobacter species may have contributed to some but probably not all of the aggregate conductivity. Microorganisms most closely related to the acetate-utilizing Methanosaeta concilii accounted for more than 90% of the sequences that could be assigned to methane producers, consistent with the poor capacity for hydrogen and formate utilization. These results demonstrate for the first time that methanogenic wastewater aggregates can be electrically conductive and suggest that direct interspecies electron transfer could be an important mechanism for electron exchange in some methanogenic systems.

Physical and Biological Controls of Copepod Aggregation and Baleen Whale Distribution

DTIC Science & Technology

2010-09-30

1 DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. Physical and Biological Controls of Copepod Aggregation...distribution. OBJECTIVES The objectives of this study are to • Elucidate the mechanisms of copepod aggregation in the Great South Channel, a...Physical and Biological Controls of Copepod Aggregation and Baleen Whale Distribution 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Protein Aggregation Inhibitors for ALS Therapy

DTIC Science & Technology

2013-07-01

mechanisms of neuronal degeneration remain unknown in ALS, it has been postulated that protein misfolding and aggregation may be an early event that...our best compounds from last year at different doses in the ALS mouse model, and investigating possible mechanisms of action of the compounds...attachment of groups for pull-down mechanism of action experiments. Table 1. SAR studies of substituted pyrazolones. Entry R1 R2 EC50 (M) a

Enhancement of particle aggregation in the presence of organic matter during neutralization of acid drainage in a stream confluence and its effect on arsenic immobilization.

PubMed

Arce, Guillermo; Montecinos, Mauricio; Guerra, Paula; Escauriaza, Cristian; Coquery, Marina; Pastén, Pablo

2017-08-01

Acid drainage (AD) is an important environmental concern that impacts water quality. The formation of reactive Fe and Al oxyhydroxides during the neutralization of AD at river confluences is a natural attenuation process. Although it is known that organic matter (OM) can affect the aggregation of Fe and Al oxyhydroxides and the sorption of As onto their surfaces, the role of OM during the neutralization of AD at river confluences has not been studied. Field and experimental approaches were used to understand this role, using the Azufre River (pH 2) - Caracarani River (pH 8.6) confluence (northern Chile) as model system. Field measurements of organic carbon revealed a 10-15% loss of OM downstream the confluence, which was attributed to associations with Fe and Al oxyhydroxides that settle in the river bed. Laboratory mixtures of AD water with synthetic Caracarani waters under varying conditions of pH, concentration and type of OM revealed that OM promoted the aggregation of Fe oxyhydroxides without reducing As sorption, enhancing the removal of As at slightly acidic conditions (pH ∼4.5). At acidic conditions (pH ∼3), aggregation of OM - metal complexes at high OM concentrations could become the main removal mechanism. One type of OM promoted bimodal particle size distributions with larger mean sizes, possibly increasing the settling velocity of aggregates. This work contributes to a better understanding of the role of OM in AD affected basins, showing that the presence of OM during processes of neutralization of AD can enhance the removal of toxic elements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of Fiber Reinforcement on the Mechanical Properties and Shrinkage Cracking of Recycled Fine Aggregate Concrete.

PubMed

Nam, Jeongsoo; Kim, Gyuyong; Yoo, Jaechul; Choe, Gyeongcheol; Kim, Hongseop; Choi, Hyeonggil; Kim, Youngduck

2016-02-26

This paper presents an experimental study conducted to investigate the effect of fiber reinforcement on the mechanical properties and shrinkage cracking of recycled fine aggregate concrete (RFAC) with two types of fiber-polyvinyl alcohol (PVA) and nylon. A small fiber volume fraction, such as 0.05% or 0.1%, in RFAC with polyvinyl alcohol or nylon fibers was used for optimum efficiency in minimum quantity. Additionally, to make a comparative evaluation of the mechanical properties and shrinkage cracking, we examined natural fine aggregate concrete as well. The test results revealed that the addition of fibers and fine aggregates plays an important role in improving the mechanical performance of the investigated concrete specimens as well as controlling their cracking behavior. The mechanical properties such as compressive strength, splitting tensile strength, and flexural strength of fiber-reinforced RFAC were slightly better than those of non-fiber-reinforced RFAC. The shrinkage cracking behavior was examined using plat-ring-type and slab-type tests. The fiber-reinforced RFAC showed a greater reduction in the surface cracks than non-fiber-reinforced concrete. The addition of fibers at a small volume fraction in RFAC is more effective for drying shrinkage cracks than for improving mechanical performance.

Effectiveness of Fiber Reinforcement on the Mechanical Properties and Shrinkage Cracking of Recycled Fine Aggregate Concrete

PubMed Central

Nam, Jeongsoo; Kim, Gyuyong; Yoo, Jaechul; Choe, Gyeongcheol; Kim, Hongseop; Choi, Hyeonggil; Kim, Youngduck

2016-01-01

This paper presents an experimental study conducted to investigate the effect of fiber reinforcement on the mechanical properties and shrinkage cracking of recycled fine aggregate concrete (RFAC) with two types of fiber—polyvinyl alcohol (PVA) and nylon. A small fiber volume fraction, such as 0.05% or 0.1%, in RFAC with polyvinyl alcohol or nylon fibers was used for optimum efficiency in minimum quantity. Additionally, to make a comparative evaluation of the mechanical properties and shrinkage cracking, we examined natural fine aggregate concrete as well. The test results revealed that the addition of fibers and fine aggregates plays an important role in improving the mechanical performance of the investigated concrete specimens as well as controlling their cracking behavior. The mechanical properties such as compressive strength, splitting tensile strength, and flexural strength of fiber-reinforced RFAC were slightly better than those of non-fiber-reinforced RFAC. The shrinkage cracking behavior was examined using plat-ring-type and slab-type tests. The fiber-reinforced RFAC showed a greater reduction in the surface cracks than non-fiber-reinforced concrete. The addition of fibers at a small volume fraction in RFAC is more effective for drying shrinkage cracks than for improving mechanical performance. PMID:28773256

Peptide concentration alters intermediate species in amyloid β fibrillation kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garvey, M., E-mail: megan.garvey@molbiotech.rwth-aachen.de; Morgado, I., E-mail: immorgado@ualg.pt

2013-04-12

Highlights: ► Aβ(1–40) aggregation in vitro has been monitored at different concentrations. ► Aβ(1–40) fibrillation does not always follow conventional kinetic mechanisms. ► We demonstrate non-linear features in the kinetics of Aβ(1–40) fibril formation. ► At high Aβ(1–40) concentrations secondary processes dictate fibrillation speed. ► Intermediate species may play significant roles on final amyloid fibril development. -- Abstract: The kinetic mechanism of amyloid aggregation remains to be fully understood. Investigations into the species present in the different kinetic phases can assist our comprehension of amyloid diseases and further our understanding of the mechanism behind amyloid β (Aβ) (1–40) peptide aggregation.more » Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) have been used in combination to monitor Aβ(1–40) aggregation in vitro at both normal and higher than standard concentrations. The observed fibrillation behaviour deviates, in several respects, from standard concepts of the nucleation–polymerisation models and shows such features as concentration-dependent non-linear effects in the assembly mechanism. Aβ(1–40) fibrillation kinetics do not always follow conventional kinetic mechanisms and, specifically at high concentrations, intermediate structures become populated and secondary processes may further modify the fibrillation mechanism.« less

Non-Arrhenius protein aggregation.

PubMed

Wang, Wei; Roberts, Christopher J

2013-07-01

Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be linked with cytotoxicity and patient immunogenicity. Therefore, investigations of protein aggregation remain a major focus in pharmaceutical companies and academic institutions. Due to the complexity of the aggregation process and temperature-dependent conformational stability, temperature-induced protein aggregation is often non-Arrhenius over even relatively small temperature windows relevant for product development, and this makes low-temperature extrapolation difficult based simply on accelerated stability studies at high temperatures. This review discusses the non-Arrhenius nature of the temperature dependence of protein aggregation, explores possible causes, and considers inherent hurdles for accurately extrapolating aggregation rates from conventional industrial approaches for selecting accelerated conditions and from conventional or more advanced methods of analyzing the resulting rate data.

Direct and Indirect Pulp Capping: A Brief History, Material Innovations, and Clinical Case Report.

PubMed

Alex, Gary

2018-03-01

Among the goals of pulp capping are to manage bacteria, arrest caries progression, stimulate pulp cells to form new dentin, and produce a durable seal that protects the pulp complex. This article will provide a general discussion of direct and indirect pulp capping procedures, offering practitioners a pragmatic and science-based clinical protocol for treatment of vital pulp exposures. A clinical case will be presented in which a novel light-cured resin-modified mineral trioxide aggregate hybrid material was used to manage a mechanical vital pulp exposure that occurred during deep caries excavation.

Entrapment of Aβ1-40 peptide in unstructured aggregates

NASA Astrophysics Data System (ADS)

Corsale, C.; Carrotta, R.; Mangione, M. R.; Vilasi, S.; Provenzano, A.; Cavallaro, G.; Bulone, D.; San Biagio, P. L.

2012-06-01

Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis.

Basalt Fiber for Volcanic Slag Lightweight Aggregate Concrete Research on the Impact of Performance

NASA Astrophysics Data System (ADS)

Xiao, Li-guang; Li, Gen-zhuang

2018-03-01

In order to study the effect of basalt fiber on the mechanical properties and durability of volcanic slag lightweight aggregate concrete, the experimental study on the flexural strength, compressive strength and freeze-thaw resistance of volcanic slag concrete with different basalt fiber content were carried out, the basalt fiber was surface treated with NaOH and water glass, the results show that the surface treatment of basalt fiber can significantly improve the mechanical properties, durability and other properties of volcanic slag lightweight aggregate concrete.

Kinetics of protein physicochemical changes induced by heating in meat using mimetic models: (1) relative effects of heat and oxidants.

PubMed

Promeyrat, A; Daudin, J D; Gatellier, P

2013-05-01

Optimizing the nutritional quality of cooked meat needs a better understanding of the mechanisms responsible for protein changes induced by heating. The relative contributions of chemical and thermal effects on protein physicochemical changes were studied using meat models. Two models were tested: a basic model made of an aqueous suspension of myofibrillar proteins, and a complex model, in which oxidants were added in physiological concentrations. Various heating time-temperature combinations were applied to both models in the ranges 45-90 °C and 5-120 min. Protein oxidation was evaluated by carbonyl and free thiol contents. Conformational changes of proteins were assessed by measurements of surface hydrophobicity and aggregation. Carbonyl formation was weakly affected by the thermal process alone but exacerbated by oxidants. A synergistic effect of oxidants and heat treatments on protein oxidation was noted. Changes in protein hydrophobicity and aggregation were dominated by the thermal process. Copyright © 2012 Elsevier Ltd. All rights reserved.

Deformation and relaxation of an incompressible viscoelastic body with surface viscoelasticity

NASA Astrophysics Data System (ADS)

Liu, Liping; Yu, Miao; Lin, Hao; Foty, Ramsey

2017-01-01

Measuring mechanical properties of cells or cell aggregates has proven to be an involved process due to their geometrical and structural complexity. Past measurements are based on material models that completely neglect the elasticity of either the surface membrane or the interior bulk. In this work, we consider general material models to account for both surface and bulk viscoelasticity. The boundary value problems are formulated for deformations and relaxations of a closed viscoelastic surface coupled with viscoelastic media inside and outside of the surface. The linearized surface elasticity models are derived for the constant surface tension model and the Helfrich-Canham bending model for coupling with the bulk viscoelasticity. For quasi-spherical surfaces, explicit solutions are obtained for the deformation, stress-strain and relaxation behaviors under a variety of loading conditions. These solutions can be applied to extract the intrinsic surface and bulk viscoelastic properties of biological cells or cell aggregates in the indentation, electro-deformation and relaxation experiments.

Differences between reversible (self-association) and irreversible aggregation of rHuG-CSF in carbohydrate and polyol formulations.

PubMed

Pavišić, Renata; Dodig, Ivana; Horvatić, Anita; Mijić, Lucija; Sedić, Mirela; Linarić, Maša Rajić; Sovulj, Ita Gruić; Preočanin, Tajana; Krajačić, Mirjana Bukvić; Cindrić, Mario

2010-11-01

Severe immunogenic and other debilitating human disorders potentially induced by protein aggregates have brought this phenomenon into the focus of biopharmaceutical science over the past decade. Depending on its driving forces, the process induced in the model protein rHuG-CSF may be either reversible or irreversible, resulting in the assembly of self-associated protein species or irreversible aggregates of various final morphologies. The aim of our work was to investigate the correlation between irreversible and reversible aggregation and the protective effect of non-specific formulation stabilisers, selected from the group of carbohydrates and polyols including trehalose, xylitol, cellobiitol, turanose, cellobiose, leucrose, lactitol, lyxose, and sorbitol, against both irreversible protein aggregation and reversible self-association processes of the rHuG-CSF. The formation of irreversible aggregates was thermally induced and evaluated using differential scanning calorimetry and size-exclusion chromatography. As opposed to the irreversible aggregation process, the process of self-association was induced by the agitation experiment by directly augmenting the protein solution contact surfaces. Absence of statistical connectivity between different stabilisers' ability to inhibit self-association or aggregation reactions indicates that these are two distinct physicochemical processes with different formulation stabilizing outcomes. Reaction mechanism of thermally induced aggregation observed in the study was in line with published literature data, while the reaction mechanism for self-association process was postulated. The postulate has been verified experimentally by isothermal calorimetry and agitation set of experiments conducted after size-exclusion chromatography and asymmetrical flow field-flow fractionation separation of monomeric, dimeric, trimeric, oligomeric, and large self-associated forms detected on multi-angle light scattering, fluorescence, UV, and refractive index detectors. Besides defining the mechanism and kinetic of self-association in stabilized rHuG-CSF formulations, special attention was also paid to the shifts and ranks of the free energy of the aggregation or self-association transition states. Copyright © 2010 Elsevier B.V. All rights reserved.

A look at construction aggregates production

USGS Publications Warehouse

Willett, Jason Christopher

2009-01-01

Construction aggregates are defined as the combination of crushed stone and construction sand and gravel. Aggregates are one of the most accessible natural resources on Earth and one of the fundamental building blocks of our society. They have been used from the earliest times of our civilization for a variety of applications that have increased in number and complexity with time and technological progress. Despite the relatively low but increasing unit value of its basic products, the construction aggregates industry is a major contributor to and an indicator of the economic well-being of the nation.

Sulfobutyl ether β-cyclodextrin (Captisol(®) ) and methyl β-cyclodextrin enhance and stabilize fluorescence of aqueous indocyanine green.

PubMed

DeDora, Daniel J; Suhrland, Cassandra; Goenka, Shilpi; Mullick Chowdhury, Sayan; Lalwani, Gaurav; Mujica-Parodi, Lilianne R; Sitharaman, Balaji

2016-10-01

As the only FDA-approved near-infrared fluorophore, indocyanine green (ICG) is commonly used to image vasculature in vivo. ICG degrades rapidly in solution, which limits its usefulness in certain applications, including time-sensitive surgical procedures. We propose formulations that address this shortcoming via complexation with β-cyclodextrin derivatives (β-CyD), which are known to create stabilizing inclusion complexes with hydrophobic molecules. Here, we complexed ICG with highly soluble methyl β-CyD and FDA-approved sulfobutyl ether β-CyD (Captisol(®) ) in aqueous solution. We measured the fluorescence of the complexes over 24 h. We found that both CyD+ICG complexes exhibit sustained fluorescence increases of >2.0× versus ICG in water and >20.0× in PBS. Using transmission electron microscopy, we found evidence of reduced aggregation in complexes versus ICG alone. We thus conclude that this reduction in aggregation helps mitigate fluorescence autoquenching of CyD+ICG complexes compared in ICG alone. We also found that while ICG complexed with methyl β-CyD severely reduced the viability of MRC-5 fibroblasts, ICG complexed with sulfobutyl ether β-CyD had no effect on viability. These results represent an important first step toward enhancing the utility of aqueous ICG by reducing aggregation-dependent fluorescence degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1457-1464, 2016. © 2015 Wiley Periodicals, Inc.

Characterization of wet aggregate stability of soils by ¹H-NMR relaxometry.

PubMed

Buchmann, C; Meyer, M; Schaumann, G E

2015-09-01

For the assessment of soil structural stability against hydraulic stress, wet sieving or constant head permeability tests are typically used but rather limited in their intrinsic information value. The multiple applications of several tests is the only possibility to assess important processes and mechanisms during soil aggregate breakdown, e.g. the influences of soil fragment release or differential swelling on the porous systems of soils or soil aggregate columns. Consequently, the development of new techniques for a faster and more detailed wet aggregate stability assessment is required. (1)H nuclear magnetic resonance relaxometry ((1)H-NMR relaxometry) might provide these requirements because it has already been successfully applied on soils. We evaluated the potential of (1)H-NMR relaxometry for the assessment of wet aggregate stability of soils, with more detailed information on occurring mechanisms at the same time. Therefore, we conducted single wet sieving and constant head permeability tests on untreated and 1% polyacrylic acid-treated soil aggregates of different textures and organic matter contents, subsequently measured by (1)H-NMR relaxometry after percolation. The stability of the soil aggregates were mainly depending on their organic matter contents and the type of aggregate stabilization, whereby additional effects of clay swelling on the measured wet aggregate stability were identified by the transverse relaxation time (T2) distributions. Regression analyses showed that only the percentage of water stable aggregates could be determined accurately from percolated soil aggregate columns by (1)H-NMR relaxometry measurements. (1)H-NMR relaxometry seems a promising technique for wet aggregate stability measurements but should be further developed for nonpercolated aggregate columns and real soil samples. Copyright © 2014 John Wiley & Sons, Ltd.

Unusual Circularly Polarized and Aggregation-Induced Near-Infrared Phosphorescence of Helical Platinum(II) Complexes with Tetradentate Salen Ligands.

PubMed

Song, Jintong; Wang, Man; Zhou, Xiangge; Xiang, Haifeng

2018-05-17

A series of chiral and helical Pt II -Salen complexes with 1,1'-binaphthyl linkers were synthesized and characterized. Owing to the restriction of intramolecular motions of central 1,1'-binaphthyls, the complexes exhibit unusual near-infrared aggregation-induced phosphorescence (AIP). The (R)/(S) enantiopure complexes were characterized by X-ray diffraction, circular dichroism spectra, time-dependent density functional theory calculations, and circularly polarized luminescence (CPL). The present work explores the use of tetradentate ligands that can be easily prepared from commercially available enantiopure compounds, and the subsequent preparation of stable CPL-active square planar Pt II complexes with AIP effect that may have interest in many applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of aggregate quality and petrographic properties' influence on rock quality: A case study from Nordland county, Norway

NASA Astrophysics Data System (ADS)

Kløve Keiding, Jakob; Erichsen, Eyolf; Heldal, Tom; Aslaksen Aasly, Kari

2017-04-01

Good access to construction materials is crucial for future infrastructure development and continued economic growth. In Norway >80 % of construction materials come from crushed aggregates and represent an growing share of the consumption. Although recycling to some extend can cover the need for construction materials, economic growth, increasing population and urbanization necessitates exploitation of new rock resources in Norway as well as many other parts of the world. Aggregates must fulfill a number of technical requirements to ensure high quality and long life expectancy of new roads, buildings and structures. Aggregates also have to be extracted near the consumer market. Particularly for road construction strict criteria are in place for wearing course for roads with high traffic density. Thus knowledge of mechanical rock quality is paramount for both exploitation as well as future resource and land-use planning but is often not assessed or mapped beyond the quarry scale. The Geological survey of Norway runs a database with information about crushed aggregate deposits from >1500 Norwegian quarries and sample sites. Here we use mechanical test analyses from the database to assess the aggregate quality in the Nordland county, Norway. Maps have been produced linking bed rock geology with rock quality parameters. The survey documents that the county is challenged in meeting the requirements for roads with high traffic density and especially in the middle parts of the county many samples have weak mechanical properties. This to some degree reflect that weak Cambro-Silurian rocks like phyllite, schist, carbonate and greenstone are abundant in Nordland. Typically mechanically stronger rock types such as gabbro, monzonite and granite are also exposed in large parts of the county, but are also characterized by relative poor or very variable mechanical test quality. Preliminary results indicate that many intrinsic parameters influence the mechanical rock strength, but variable degrees of deformation in the different tectonostratigraphic units exposed in Nordland affects the rock mechanical properties and is a prominent feature of our mapping. Unsurprisingly rock type, mineralogy, grain size and rock texture are all important factors that have a major control on the mechanical behaviour of the rocks. However, this assessment shows that there is an intricate interaction between these parameters and the resulting mechanical properties at present making it difficult to assess mechanical quality accurately only based on petrographic examination.

Formation of wormlike aggregates of fluorocarbon-hydrocarbon hybrid surfactant by Langmuir-Blodgett transfer and alignment of gold nanoparticles.

PubMed

Kondo, Yukishige; Fukuoka, Hiroshi; Nakano, Shuichi; Hayashi, Kohei; Tsukagoshi, Tatsuya; Matsumoto, Mutsuyoshi; Yoshino, Norio

2007-05-22

A novel anionic fluorocarbon-hydrocarbon hybrid surfactant (SS-Hyb-Na+) with a disulfide group has been synthesized from 11-bromo-1-undecanal and perfluorohexylethyl iodide via three steps. The Langmuir-Blodgett (LB) transfer of the 1:100 (mol/mol) mixed monolayer of SS-Hyb-Na+ and stearyl alcohol (C18OH) formed on an aqueous solution containing a cationic polymer, poly(diallyldimethylammonium chloride) (PDDA+Cl-) onto a hydrophobic silicon wafer yields the formation of wormlike aggregates consisting of SS-Hyb-/PDDA+ polyion complexes. It is found that the aggregates align along the withdrawal direction of the wafer substrate. When the wafer on which the wormlike aggregates exist is immersed into the dispersion of gold nanoparticles (Au NPs) prepared by the citrate reduction method, Au NPs align along the wormlike structures. Even though the surface of the wafer is placed either vertical or parallel to the monolayer compression direction during the LB transfer, the one-dimensional (1D) array of Au NPs is observed along the withdrawal direction of the wafer. This indicates that the wormlike aggregates of SS-Hyb-/PDDA+ complexes are aligned during the LB transfer, and the aligned aggregates behave as a scaffold in the 1D array of Au NPs.

A microfabricated platform to form three-dimensional toroidal multicellular aggregate.

PubMed

Masuda, Taisuke; Takei, Natsuki; Nakano, Takuma; Anada, Takahisa; Suzuki, Osamu; Arai, Fumihito

2012-12-01

Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid microtissues provide powerful in vitro models that are becoming increasingly popular in fields such as stem cell research, tissue engineering, and cancer biology. Appropriate simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. We have developed a unique multicellular aggregate formation platform that utilizes a maskless gray-scale photolithography. The cellular aggregate formed using this platform has a toroidal-like geometry and includes a micro lumen that facilitates the supply of oxygen and growth factors and the expulsion of waste products. As a result, this platform was capable of rapidly producing hundreds of multicellular aggregates at a time, and of regulating the diameter of aggregates with complex design. These toroidal multicellular aggregates can grow as long-term culture. In addition, the micro lumen can be used as a continuous channel and for the insertion of a vascular system or a nerve system into the assembled tissue. These platform characteristics highlight its potential to be used in a wide variety of applications, e.g. as a bioactuator, as a micro-machine component or in drug screening and tissue engineering.

Estimating genetic effects and quantifying missing heritability explained by identified rare-variant associations.

PubMed

Liu, Dajiang J; Leal, Suzanne M

2012-10-05

Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner's curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study where the association is identified. This is because there can be substantial heterogeneity of RV sites and frequencies even among closely related populations. In order to obtain an unbiased estimate for aggregated RV analysis, we developed bootstrap-sample-split algorithms to reduce the bias of the winner's curse. The unbiased estimates are greatly important for understanding the population-specific contribution of RVs to the heritability of complex traits. We also demonstrate both theoretically and via simulations that for aggregate RV analysis the genetic variance for a gene or region will always be underestimated, sometimes substantially, because of the presence of noncausal variants or because of the presence of causal variants with effects of different magnitudes or directions. Therefore, even if RVs play a major role in the complex-trait etiologies, a portion of the heritability will remain missing, and the contribution of RVs to the complex-trait etiologies will be underestimated. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A truncated and dimeric format of an Affibody library on bacteria enables FACS-mediated isolation of amyloid-beta aggregation inhibitors with subnanomolar affinity.

PubMed

Lindberg, Hanna; Härd, Torleif; Löfblom, John; Ståhl, Stefan

2015-09-01

The amyloid hypothesis suggests that accumulation of amyloid β (Aβ) peptides in the brain is involved in development of Alzheimer's disease. We previously generated a small dimeric affinity protein that inhibited Aβ aggregation by sequestering the aggregation prone parts of the peptide. The affinity protein is originally based on the Affibody scaffold, but is evolved to a distinct interaction mechanism involving complex structural rearrangement in both the Aβ peptide and the affinity proteins upon binding. The aim of this study was to decrease the size of the dimeric affinity protein and significantly improve its affinity for the Aβ peptide to increase its potential as a future therapeutic agent. We combined a rational design approach with combinatorial protein engineering to generate two different affinity maturation libraries. The libraries were displayed on staphylococcal cells and high-affinity Aβ-binding molecules were isolated using flow-cytometric sorting. The best performing candidate binds Aβ with a KD value of around 300 pM, corresponding to a 50-fold improvement in affinity relative to the first-generation binder. The new dimeric Affibody molecule was shown to capture Aβ1-42 peptides from spiked E. coli lysate. Altogether, our results demonstrate successful engineering of this complex binder for increased affinity to the Aβ peptide. © 2015 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Aggregate Exposure and Cumulative Risk Assessment—Integrating Occupational and Non-occupational Risk Factors

PubMed Central

Lentz, T. J.; Dotson, G. S.; Williams, P. R.D.; Maier, A.; Gadagbui, B.; Pandalai, S. P.; Lamba, A.; Hearl, F.; Mumtaz, M.

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational. PMID:26583907

Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

PubMed

Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

Mesoscale Fracture Analysis of Multiphase Cementitious Composites Using Peridynamics

PubMed Central

Yaghoobi, Amin; Chorzepa, Mi G.; Kim, S. Sonny; Durham, Stephan A.

2017-01-01

Concrete is a complex heterogeneous material, and thus, it is important to develop numerical modeling methods to enhance the prediction accuracy of the fracture mechanism. In this study, a two-dimensional mesoscale model is developed using a non-ordinary state-based peridynamic (NOSBPD) method. Fracture in a concrete cube specimen subjected to pure tension is studied. The presence of heterogeneous materials consisting of coarse aggregates, interfacial transition zones, air voids and cementitious matrix is characterized as particle points in a two-dimensional mesoscale model. Coarse aggregates and voids are generated using uniform probability distributions, while a statistical study is provided to comprise the effect of random distributions of constituent materials. In obtaining the steady-state response, an incremental and iterative solver is adopted for the dynamic relaxation method. Load-displacement curves and damage patterns are compared with available experimental and finite element analysis (FEA) results. Although the proposed model uses much simpler material damage models and discretization schemes, the load-displacement curves show no difference from the FEA results. Furthermore, no mesh refinement is necessary, as fracture is inherently characterized by bond breakages. Finally, a sensitivity study is conducted to understand the effect of aggregate volume fraction and porosity on the load capacity of the proposed mesoscale model. PMID:28772518

Pattern formation in Dictyostelium discoideum aggregates in confined microenvironments

NASA Astrophysics Data System (ADS)

Hallou, Adrien; Hersen, Pascal; di Meglio, Jean-Marc; Kabla, Alexandre

Dictyostelium Discoideum (Dd) is often viewed as a model system to study the complex collective cell behaviours which shape an embryo. Under starvation, Dd cells form multicellular aggregates which soon elongate, starting to display an anterior-posterior axis by differentiating into two distinct cell populations; prestalk (front) and prespore (rear) cells zones. Different models, either based on positional information or on differentiation followed up by cell sorting, have been proposed to explain the origin and the regulation of this spatial pattern.To decipher between the proposed hypotheses, we have developed am experimental platform where aggregates, made of genetically engineered Dd cells to express fluorescent reporters of cell differentiation in either prestalk or prespore cells, are allowed to develop in 20 to 400 μm wide hydrogel channels. Such a setup allows us to both mimic Dd confined natural soil environment and to follow the patterning dynamics using time-lapse microscopy. Tracking cell lineage commitments and positions in space and time, we demonstrate that Dd cells differentiate first into prestalk and prespore cells prior to sorting into an organized spatial pattern on the basis of collective motions based on differential motility and adhesion mechanisms. A. Hallou would like to thank the University of Cambridge for the Award of an ``Oliver Gatty Studentship in Biophysical and Colloid Science''.

Cellular Strategies for Regulating Functional and Nonfunctional Protein Aggregation

PubMed Central

Gsponer, Jörg; Babu, M. Madan

2012-01-01

Summary Growing evidence suggests that aggregation-prone proteins are both harmful and functional for a cell. How do cellular systems balance the detrimental and beneficial effect of protein aggregation? We reveal that aggregation-prone proteins are subject to differential transcriptional, translational, and degradation control compared to nonaggregation-prone proteins, which leads to their decreased synthesis, low abundance, and high turnover. Genetic modulators that enhance the aggregation phenotype are enriched in genes that influence expression homeostasis. Moreover, genes encoding aggregation-prone proteins are more likely to be harmful when overexpressed. The trends are evolutionarily conserved and suggest a strategy whereby cellular mechanisms specifically modulate the availability of aggregation-prone proteins to (1) keep concentrations below the critical ones required for aggregation and (2) shift the equilibrium between the monomeric and oligomeric/aggregate form, as explained by Le Chatelier’s principle. This strategy may prevent formation of undesirable aggregates and keep functional assemblies/aggregates under control. PMID:23168257

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates.

PubMed

Egorov, Vladimir V

2017-05-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E.

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates

PubMed Central

2017-01-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E. PMID:28572984

Nature of the optical band shapes in polymethine dyes and H-aggregates: dozy chaos and excitons. Comparison with dimers, H*- and J-aggregates

NASA Astrophysics Data System (ADS)

Egorov, Vladimir V.

2017-05-01

Results on the theoretical explanation of the shape of optical bands in polymethine dyes, their dimers and aggregates are summarized. The theoretical dependence of the shape of optical bands for the dye monomers in the vinylogous series in line with a change in the solvent polarity is considered. A simple physical (analytical) model of the shape of optical absorption bands in H-aggregates of polymethine dyes is developed based on taking the dozy-chaos dynamics of the transient state and the Frenkel exciton effect in the theory of molecular quantum transitions into account. As an example, the details of the experimental shape of one of the known H-bands are well reproduced by this analytical model under the assumption that the main optical chromophore of H-aggregates is a tetramer resulting from the two most probable processes of inelastic binary collisions in sequence: first, monomers between themselves, and then, between the resulting dimers. The obtained results indicate that in contrast with the compact structure of J-aggregates (brickwork structure), the structure of H-aggregates is not the compact pack-of-cards structure, as stated in the literature, but a loose alternate structure. Based on this theoretical model, a simple general (analytical) method for treating the more complex shapes of optical bands in polymethine dyes in comparison with the H-band under consideration is proposed. This method mirrors the physical process of molecular aggregates forming in liquid solutions: aggregates are generated in the most probable processes of inelastic multiple binary collisions between polymethine species generally differing in complexity. The results obtained are given against a background of the theoretical results on the shape of optical bands in polymethine dyes and their aggregates (dimers, H*- and J-aggregates) previously obtained by V.V.E.

The Endoplasmic Reticulum-Associated Degradation Pathways of Budding Yeast

PubMed Central

Thibault, Guillaume; Ng, Davis T.W.

2012-01-01

Protein misfolding is a common cellular event that can produce intrinsically harmful products. To reduce the risk, quality control mechanisms are deployed to detect and eliminate misfolded, aggregated, and unassembled proteins. In the secretory pathway, it is mainly the endoplasmic reticulum-associated degradation (ERAD) pathways that perform this role. Here, specialized factors are organized to monitor and process the folded states of nascent polypeptides. Despite the complex structures, topologies, and posttranslational modifications of client molecules, the ER mechanisms are the best understood among all protein quality-control systems. This is the result of convergent and sometimes serendipitous discoveries by researchers from diverse fields. Although major advances in ER quality control and ERAD came from all model organisms, this review will focus on the discoveries culminating from the simple budding yeast. PMID:23209158

RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease.

PubMed

Bishof, Isaac; Dammer, Eric B; Duong, Duc M; Kundinger, Sean; Gearing, Marla; Lah, James J; Levey, Allan I; Seyfried, Nicholas T

2018-05-25

U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and other RNA-binding proteins (RBPs) are mislocalized to cytoplasmic neurofibrillary tau aggregates in Alzheimer's disease (AD), yet the co-aggregation mechanisms are incompletely understood. U1-70K harbors two disordered low-complexity domains (LC1 and LC2) that are necessary for aggregation in AD brain extracts. The LC1 domain contains highly repetitive basic (R/K) and acidic (D/E) residues, referred to as a basic-acidic dipeptide (BAD) domain. We report here that this domain shares many of the properties of the Q/N-rich LC domains in RBPs that also aggregate in neurodegenerative disease. These properties included self-assembly into oligomers and localization to nuclear granules. Co-immunoprecipitations of recombinant U1-70K and deletions lacking the LC domain(s) followed by quantitative proteomic analyses were used to resolve functional classes of U1-70K-interacting proteins that depend on the BAD domain for their interaction. Within this interaction network, we identified a class of RBPs with BAD domains nearly identical to that found in U1-70K. Two members of this class, LUC7L3 and RBM25, required their respective BAD domains for reciprocal interactions with U1-70K and nuclear granule localization. Strikingly, a significant proportion of RBPs with BAD domains had elevated insolubility in the AD brain proteome. Furthermore, we show that the BAD domain of U1-70K can interact with tau from AD brains, but not from other tauopathies. These findings highlight a mechanistic role for BAD domains in stabilizing RBP interactions and in potentially mediating co-aggregation with pathological, AD-specific tau isoforms. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation.

PubMed

Lou, Zhichao; Wang, Bin; Guo, Cunlan; Wang, Kun; Zhang, Haiqian; Xu, Bingqian

2015-11-01

By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. Copyright © 2015 Elsevier B.V. All rights reserved.

An experimental study on the hazard assessment and mechanical properties of porous concrete utilizing coal bottom ash coarse aggregate in Korea.

PubMed

Park, Seung Bum; Jang, Young Il; Lee, Jun; Lee, Byung Jae

2009-07-15

This study evaluates quality properties and toxicity of coal bottom ash coarse aggregate and analyzes mechanical properties of porous concrete depending on mixing rates of coal bottom ash. As a result, soundness and resistance to abrasion of coal bottom ash coarse aggregate were satisfied according to the standard of coarse aggregate for concrete. To satisfy the standard pertaining to chloride content, the coarse aggregates have to be washed more than twice. In regards to the result of leaching test for coal bottom ash coarse aggregate and porous concrete produced with these coarse aggregates, it was satisfied with the environment criteria. As the mixing rate of coal bottom ash increased, influence of void ratio and permeability coefficient was very little, but compressive and flexural strength decreased. When coal bottom ash was mixed over 40%, strength decreased sharply (compressive strength: by 11.7-27.1%, flexural strength: by maximum 26.4%). Also, as the mixing rate of coal bottom ash increased, it was confirmed that test specimens were destroyed by aggregate fracture more than binder fracture and interface fracture. To utilize coal bottom ash in large quantities, it is thought that an improvement method in regards to strength has to be discussed such as incorporation of reinforcing materials and improvement of aggregate hardness.

Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).

PubMed

Ciaccio, Natalie A; Reynolds, T Steele; Middaugh, C Russell; Laurence, Jennifer S

2012-11-05

Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and nonreducing conditions. Our data indicate that removal of this region results in a loss of α-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation.

Effects of recombinant protein misfolding and aggregation on bacterial membranes.

PubMed

Ami, D; Natalello, A; Schultz, T; Gatti-Lafranconi, P; Lotti, M; Doglia, S M; de Marco, A

2009-02-01

The expression of recombinant proteins is known to induce a metabolic rearrangement in the host cell. We used aggregation-sensitive model systems to study the effects elicited in Escherichia coli cells by the aggregation of recombinant glutathione-S-transferase and its fusion with the green fluorescent protein that, according to the expression conditions, accumulate intracellularly as soluble protein, or soluble and insoluble aggregates. We show that the folding state of the recombinant protein and the complexity of the intracellular aggregates critically affect the cell response. Specifically, protein misfolding and aggregation induce changes in specific host proteins involved in lipid metabolism and oxidative stress, a reduction in the membrane permeability, as well as a rearrangement of its lipid composition. The temporal evolution of the host cell response and that of the aggregation process pointed out that the misfolded protein and soluble aggregates are responsible for the membrane modifications and the changes in the host protein levels. Interestingly, native recombinant protein and large insoluble aggregates do not seem to activate stress markers and membrane rearrangements.

Physical and Biological Controls of Copepod Aggregation and Baleen Whale Distribution

DTIC Science & Technology

2011-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Physical and Biological Controls of Copepod Aggregation and...DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Physical and Biological Controls of Copepod Aggregation and Baleen Whale Distribution...OBJECTIVES The objectives of this study are to: • Elucidate the mechanisms of copepod aggregation in the Great South Channel, a major

The influence of local mechanisms on large scale seismic vulnerability estimation of masonry building aggregates

NASA Astrophysics Data System (ADS)

Formisano, Antonio; Chieffo, Nicola; Milo, Bartolomeo; Fabbrocino, Francesco

2016-12-01

The current paper deals with the seismic vulnerability evaluation of masonry constructions grouped in aggregates through an "ad hoc" quick vulnerability form based on new assessment parameters considering local collapse mechanisms. First, a parametric kinematic analysis on masonry walls with different height (h) / thickness (t) ratios has been developed with the purpose of identifying the collapse load multiplier for activation of the main four first-order failure mechanisms. Subsequently, a form initially conceived for building aggregates suffering second-mode collapse mechanisms, has been expanded on the basis of the achieved results. Tre proposed quick vulnerability technique has been applied to one case study within the territory of Arsita (Teramo, Italy) and, finally, it has been also validated by the comparison of results with those deriving from application of the well-known FaMIVE procedure.

Mechanochemical Symmetry Breaking in Hydra Aggregates

PubMed Central

Mercker, Moritz; Köthe, Alexandra; Marciniak-Czochra, Anna

2015-01-01

Tissue morphogenesis comprises the self-organized creation of various patterns and shapes. Although detailed underlying mechanisms are still elusive in many cases, an increasing amount of experimental data suggests that chemical morphogen and mechanical processes are strongly coupled. Here, we develop and test a minimal model of the axis-defining step (i.e., symmetry breaking) in aggregates of the Hydra polyp. Based on previous findings, we combine osmotically driven shape oscillations with tissue mechanics and morphogen dynamics. We show that the model incorporating a simple feedback loop between morphogen patterning and tissue stretch reproduces a wide range of experimental data. Finally, we compare different hypothetical morphogen patterning mechanisms (Turing, tissue-curvature, and self-organized criticality). Our results suggest the experimental investigation of bigger (i.e., multiple head) aggregates as a key step for a deeper understanding of mechanochemical symmetry breaking in Hydra. PMID:25954896

Secure data aggregation in wireless sensor networks using homomorphic encryption

NASA Astrophysics Data System (ADS)

Kumar, Manish; Verma, Shekhar; Lata, Kusum

2015-04-01

In a Wireless Sensor Network (WSN), aggregation exploits the correlation between spatially and temporally proximate sensor data to reduce the total data volume to be transmitted to the sink. Mobile agents (MAs) fit into this paradigm, and data can be aggregated and collected by an MA from different sensor nodes using context specific codes. The MA-based data collection suffers due to large size of a typical WSN and is prone to security problems. In this article, homomorphic encryption in a clustered WSN has been proposed for secure and efficient data collection using MAs. The nodes keep encrypted data that are given to an MA for data aggregation tasks. The MA performs all the data aggregation operations upon encrypted data as it migrates between nodes in a tree-like structure in which the nodes are leafs and the cluster head is the root of the tree. It returns and deposits the encrypted aggregated data to the cluster head after traversing through all the intra cluster nodes over a shortest path route. The homomorphic encryption and aggregation processing in encrypted domain makes the data collection process secure. Simulation results confirm the effectiveness of the proposed secure data aggregation mechanism. In addition to security, MA-based mechanism leads to lesser delay and bandwidth requirements.

Ceramic ware waste as coarse aggregate for structural concrete production.

PubMed

García-González, Julia; Rodríguez-Robles, Desirée; Juan-Valdés, Andrés; Morán-Del Pozo, Julia M; Guerra-Romero, M Ignacio

2015-01-01

The manufacture of any kind of product inevitably entails the production of waste. The quantity of waste generated by the ceramic industry, a very important sector in Spain, is between 5% and 8% of the final output and it is therefore necessary to find an effective waste recovery method. The aim of the study reported in the present article was to seek a sustainable means of managing waste from the ceramic industry through the incorporation of this type of waste in the total replacement of conventional aggregate (gravel) used in structural concrete. Having verified that the recycled ceramic aggregates met all the technical requirements imposed by current Spanish legislation, established in the Code on Structural Concrete (EHE-08), then it is prepared a control concrete mix and the recycled concrete mix using 100% recycled ceramic aggregate instead of coarse natural aggregate. The concretes obtained were subjected to the appropriate tests in order to conduct a comparison of their mechanical properties. The results show that the concretes made using ceramic sanitary ware aggregate possessed the same mechanical properties as those made with conventional aggregate. It is therefore possible to conclude that the reuse of recycled ceramic aggregate to produce recycled concrete is a feasible alternative for the sustainable management of this waste.

Heating of Porous Icy Dust Aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirono, Sin-iti

At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H{sub 2}O ice. Because H{sub 2}O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. Themore » mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.« less

Mechanisms of Ricin Toxin Neutralization Revealed through Engineered Homodimeric and Heterodimeric Camelid Antibodies*

PubMed Central

Herrera, Cristina; Tremblay, Jacqueline M.; Shoemaker, Charles B.; Mantis, Nicholas J.

2015-01-01

Novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (VHHs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against Shiga, botulinum, Clostridium difficile, anthrax, and ricin toxins. However, the mechanisms by which these so-called bispecific VHH heterodimers promote toxin neutralization remain poorly understood. In the current study we produced a new collection of ricin-specific VHH heterodimers, as well as VHH homodimers, and characterized them for their ability neutralize ricin in vitro and in vivo. We demonstrate that the VHH heterodimers, but not homodimers were able to completely protect mice against ricin challenge, even though the two classes of antibodies (heterodimers and homodimers) had virtually identical affinities for ricin holotoxin and similar IC50 values in a Vero cell cytotoxicity assay. The VHH heterodimers did differ from the homodimers in their ability to promote toxin aggregation in solution, as revealed through analytical ultracentrifugation. Moreover, the VHH heterodimers that were most effective at promoting ricin aggregation in solution were also the most effective at blocking ricin attachment to cell surfaces. Collectively, these data suggest that heterodimeric VHH-based neutralizing agents may function through the formation of antibody-toxin complexes that are impaired in their ability to access host cell receptors. PMID:26396190

Protein Self-Assembly and Protein-Induced DNA Morphologies

NASA Astrophysics Data System (ADS)

Mawhinney, Matthew T.

The ability of biomolecules to associate into various structural configurations has a substantial impact on human physiology. The synthesis of protein polypeptide chains using the information encoded by DNA is mediated through the use of regulatory proteins, known as transcription factors. Some transcription factors perform function by inducing local curvature in deoxyribonucleic acid (DNA) strands, the mechanisms of which are not entirely known. An important architectural protein, eleven zinc finger CTCF (11 ZF CTCF) is involved in genome organization and hypothesized to mediate DNA loop formation. Direct evidence for these CTCF-induced DNA loops has yet to be observed. In this thesis, the effect of 11 ZF CTCF on DNA morphology is examined using atomic force microscopy, a powerful technique for visualizing biomolecules with nanometer resolution. The presence of CTCF is revealed to induce a variety of morphologies deviating from the relaxed state of control DNA samples, including compact circular complexes, meshes, and networks. Images reveal quasi-circular DNA/CTCF complexes consistent with a single DNA molecule twice wrapped around the protein. The structures of DNA and proteins are highly important for operations in the cell. Structural irregularities may lead to a variety of issues, including more than twenty human pathologies resulting from aberrant protein misfolding into amyloid aggregates of elongated fibrils. Insulin deficiency and resistance characterizing type 2 diabetes often requires administration of insulin. Injectable and inhalable delivery methods have been documented to result in the deposition of amyloid fibrils. Oligomers, soluble multiprotein assemblies, are believed to play an important role in this process. Insulin aggregation under physiological conditions is not well understood and oligomers have not yet been fully characterized. In this thesis, in vitro insulin aggregation at acidic and neutral pH is explored using a variety of techniques, including kinetic thioflavin T fluorescence, circular dichroism spectroscopy, atomic force and electron microscopy imaging. The size distribution of insulin oligomers at different assembly stages is characterized through covalent cross-linking and gel electrophoresis. Results show that at the earliest assembly stage, oligomers comprise up to 40% and 70% of soluble insulin at acidic and neutral pH, respectively. While the highest oligomer order increases with insulin concentration at acidic pH, the opposite tendency is observed at neutral pH, with heptamers formed in 10 muM insulin. These findings suggest that oligomers may be on- and off- pathway assemblies for insulin at acidic and neutral pH, respectively. Agitation, required to induce insulin aggregation at neutral pH, increases fibril formation rate and fibrillar mass by an order of magnitude each. Insulin incubated under agitated conditions at neutral pH rapidly aggregates into large micrometer-sized aggregates, which provides insight into injection-site amyloidosis and toxic pulmonary aggregates induced by administration of extraneous insulin.

Nano-aggregates: emerging delivery tools for tumor therapy.

PubMed

Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

2013-01-01

A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

Growth-incompetent monomers of human calcitonin lead to a noncanonical direct relationship between peptide concentration and aggregation lag time.

PubMed

Kamgar-Parsi, Kian; Hong, Liu; Naito, Akira; Brooks, Charles L; Ramamoorthy, Ayyalusamy

2017-09-08

The role of the peptide hormone calcitonin in skeletal protection has led to its use as a therapeutic for osteoporosis. However, calcitonin aggregation into amyloid fibrils limits its therapeutic efficacy, necessitating a modification of calcitonin's aggregation kinetics. Here, we report a direct relationship between human calcitonin (hCT) concentration and aggregation lag time. This kinetic trend was contrary to the conventional understanding of amyloid aggregation and persisted over a range of aggregation conditions, as confirmed by thioflavin-T kinetics assays, CD spectroscopy, and transmission EM. Dynamic light scattering, 1 H NMR experiments, and seeded thioflavin-T assay results indicated that differences in initial peptide species contribute to this trend more than variations in the primary nucleus formation rate. On the basis of kinetics modeling results, we propose a mechanism whereby a structural conversion of hCT monomers is needed before incorporation into the fibril. Our kinetic mechanism recapitulates the experimentally observed relationship between peptide concentration and lag time and represents a novel mechanism in amyloid aggregation. Interestingly, hCT at low pH and salmon calcitonin (sCT) exhibited the canonical inverse relationship between concentration and lag time. Comparative studies of hCT and sCT with molecular dynamics simulations and CD indicated an increased α-helical structure in sCT and low-pH hCT monomers compared with neutral-pH hCT, suggesting that α-helical monomers represent a growth-competent species, whereas unstructured random coil monomers represent a growth-incompetent species. Our finding that initial monomer concentration is positively correlated with lag time in hCT aggregation could help inform future efforts for improving therapeutic applications of CT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Prothrombotic mechanisms in patients with congenital p.Cys89Tyr mutation in CD59.

PubMed

Tabib, Adi; Hindi, Issam; Karbian, Netanel; Zelig, Orly; Falach, Batla; Mevorach, Dror

2018-06-11

Thrombosis is the prognostic factor with the greatest effect on survival in patients with paroxysmal nocturnal hemoglobinuria (PNH), who lack dozens of membrane surface proteins. We recently described a primary homozygous Cys89Tyr congenital nonfunctioning CD59 in humans with clinical manifestation in infancy, associated with chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy. Here we investigated hypercoagulability mechanisms characterizing the syndrome. Membrane attack complex (MAC) deposition (anti-SC5b-9) and free hemoglobin (colorimetric assay) were assessed. Platelet activation was identified (anti-CD61, anti-CD62P), and microparticles (MPs) of 0.5-0.9 μm, were characterized (Annexin V, anti-human GlyA, anti-CD15, anti-CD14, anti-CD61). Platelet-monocyte aggregation was assessed with FlowSight. 2/7 patients (29%) with homozygosity for Cys89Tyr and 6/12 (50%) with any of four described CD59 mutations had recurrent strokes. In plasma samples from four patients carrying identical mutations, MAC deposition was increased on RBCs (p < 0.0003), neutrophils (p < 0.009), and platelets (p < 0.0003). Free-plasma hemoglobin levels were abnormally high, up to 100 mg/dl. Patients with CD59 mutation had RBC-derived MP levels 9-fold higher than those in healthy controls (p < 0.01), and 2-2.5 fold higher than PNH patients (p < 0.09). Leukocyte-activated platelet aggregation was increased (p < 0.0062). Loss of CD59 was shown in the endothelium of these patients. Nonfunctioning CD59 is a major risk factor for stroke and hypercoagulability. Uncontrolled hemolysis causes massive MP release and endothelial heme damage. MAC attack on unprotected endothelium and platelet activation and aggregation with leukocytes mediate additional mechanisms leading to vascular occlusion. It is suggested that CD59 loss represents a major arterial prothrombotic factor in PNH and additional diseases. Copyright © 2018. Published by Elsevier Ltd.

αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid β-peptide and β2-microglobulin

PubMed Central

2005-01-01

αB-crystallin, a small heat-shock protein, exhibits molecular chaperone activity. We have studied the effect of αB-crystallin on the fibril growth of the Aβ (amyloid β)-peptides Aβ-(1–40) and Aβ-(1–42). αB-crystallin, but not BSA or hen egg-white lysozyme, prevented the fibril growth of Aβ-(1–40), as revealed by thioflavin T binding, total internal reflection fluorescence microscopy and CD spectroscopy. Comparison of the activity of some mutants and chimaeric α-crystallins in preventing Aβ-(1–40) fibril growth with their previously reported chaperone ability in preventing dithiothreitol-induced aggregation of insulin suggests that there might be both common and distinct sites of interaction on α-crystallin involved in the prevention of amorphous aggregation of insulin and fibril growth of Aβ-(1–40). αB-crystallin also prevents the spontaneous fibril formation (without externally added seeds) of Aβ-(1–42), as well as the fibril growth of Aβ-(1–40) when seeded with the Aβ-(1–42) fibril seed. Sedimentation velocity measurements show that αB-crystallin does not form a stable complex with Aβ-(1–40). The mechanism by which it prevents the fibril growth differs from the known mechanism by which it prevents the amorphous aggregation of proteins. αB-crystallin binds to the amyloid fibrils of Aβ-(1–40), indicating that the preferential interaction of the chaperone with the fibril nucleus, which inhibits nucleation-dependent polymerization of amyloid fibrils, is the mechanism that is predominantly involved. We found that αB-crystallin prevents the fibril growth of β2-microglobulin under acidic conditions. It also retards the depolymerization of β2-microglobulin fibrils, indicating that it can interact with the fibrils. Our study sheds light on the role of small heat-shock proteins in protein conformational diseases, particularly in Alzheimer's disease. PMID:16053447

Arbuscular mycorrhizal fungi make a complex contribution to soil aggregation

NASA Astrophysics Data System (ADS)

McGee, Peter; Daynes, Cathal; Damien, Field

2013-04-01

Soil aggregates contain solid and fluid components. Aggregates develop as a consequence of the organic materials, plants and hyphae of arbuscular mycorrhizal (AM) fungi acting on the solid phase. Various correlative studies indicate hyphae of AM fungi enmesh soil particles, but their impact on the pore space is poorly understood. Hyphae may penetrate between particles, remove water from interstitial spaces, and otherwise re-arrange the solid phase. Thus we might predict that AM fungi also change the pore architecture of aggregates. Direct observations of pore architecture of soil, such as by computer-aided tomography (CT), is difficult. The refractive natures of solid and biological material are similar. The plant-available water in various treatments allows us to infer changes in pore architecture. Our experimental studies indicate AM fungi have a complex role in the formation and development of aggregates. Soils formed from compost and coarse subsoil materials were planted with mycorrhizal or non-mycorrhizal seedlings and the resultant soils compared after 6 or 14 months in separate experiments. As well as enmeshing particles, AM fungi were associated with the development of a complex pore space and greater pore volume. Even though AM fungi add organic matter to soil, the modification of pore space is not correlated with organic carbon. In a separate study, we visualised hyphae of AM fungi in a coarse material using CT. In this study, hyphae appeared to grow close to the surfaces of particles with limited ramification across the pore spaces. Hyphae of AM fungi appear to utilise soil moisture for their growth and development of mycelium. The strong correlation between moisture and hyphae has profound implications for soil aggregation, plant utilisation of soil water, and the distribution of water as water availability declines.

Effects of aggregation on the excitation dynamics of LH2 from Thermochromatium tepidum in aqueous phase and in chromatophores.

PubMed

Yang, Fan; Yu, Long-Jiang; Wang, Peng; Ai, Xi-Cheng; Wang, Zheng-Yu; Zhang, Jian-Ping

2011-06-23

We carried out femtosecond magic-angle and polarized pump-probe spectroscopies for the light-harvesting complex 2 (LH2) from Thermochromatium (Tch.) tepidum in aqueous phase and in chromatophores. To examine the effects of LH2 aggregation on the dynamics of excitation energy transfer, dominant monodispersed and aggregated LH2s were prepared by controlling the surfactant concentrations. The aqueous preparations solubilized with different concentrations of n-dodecyl-β-D-maltoside (DDM) show similar visible-to-near-infrared absorption spectra, but distinctively different aggregation states, as revealed by using dynamic light scattering. The B800 → B850 intra-LH2 energy transfer time was determined to be 1.3 ps for isolated LH2, which, upon aggregation in aqueous phase or clustering in chromatophores, shortened to 1.1 or 0.9 ps, respectively. The light-harvesting complex 1 (LH1) of this thermophilic purple sulfur bacterium contains bacteriochlorophyll a absorbing at 915 nm (B915), and the LH2(B850) → LH1(B915) intercomplex transfer time in chromatophores was found to be 6.6 ps. For chromatophores, a depolarization time of 21 ps was derived from the anisotropy kinetics of B850*, which is attributed to the migration of B850* excitation before being trapped by LH1. In addition, the B850* annihilation is accelerated upon LH2 aggregation in aqueous phase, but it is much less severe upon LH2 clustering in the intracytoplasmic membrane. These results are helpful in understanding the light-harvesting function of a bacterial photosynthetic membrane incorporating different types of antenna complexes.

STXM/C 1s-NEXAFS study of Eu(III) and Uranyl humic acid aggregates at different pH

NASA Astrophysics Data System (ADS)

Plaschke, M.; Rothe, J.; Denecke, M. A.; Geckeis, H.

2010-04-01

Humic acids (HA) are chemically heterogeneous and structurally ill-defined biopolymers which are able to bind traces of actinides or lanthanides. Due to their dimensions in the colloidal size range they may affect transport of these elements in aquatic systems. Eu(III)- and UO22+-HA aggregates have been investigated by Scanning Transmission X-ray Microscopy (STXM) and C 1s-NEXAFS under systematic variation of pH. In the Eu(III)- and UO22+-HA systems aggregate morphologies at near neutral pH were similar to those observed in previous studies: optically dense zones (high absorption at the carbon K-edge) are embedded in a matrix of less dense material. C 1s-NEXAFS signatures observed in the different zones, i.e., the intensity of the characteristic complexation feature previously experimentally described and recently theoretically characterized, strongly depends on sample pH. In the alkaline regime (pH 9) with added carbonate, co-precipitation of Eu(III)-carbonate (or ternary carbonate/(oxo)hydroxide complexes) with the Eu(III)-HA majority fraction is observed but Eu(III) binding to HA over carbonate in the dense zones seems to be favoured. The UO22+-HA system exhibits in alkaline solution more compact morphologies combined with a strong metal ion complexation effect in the NEXAFS. Eu(III) and UO22+ polyacrylic acid (PAA) aggregates used as HA model systems show similar spectral trends; these aggregates exhibit highly branched morphologies without segregation into zones with different NEXAFS signatures. The chemical environment such as pH or the type of metal cation strongly influences both HA aggregate morphologies and NEXAFS spectral signatures. These can, in turn, be used as indicators of the strength of lanthanide or actinide ion bound HA interaction.

Quantification of the proliferation of arbuscular mycorrhizal fungi in soil

NASA Astrophysics Data System (ADS)

Zhang, Ning; Lilje, Osu; McGee, Peter

2013-04-01

Good soil structure is important for sustaining agricultural production and preserving functions of the soil ecosystem. Soil aggregation is a critically important component of soil structure. Stable aggregates enable water infiltration, gas exchange for biological activities of plant roots and microorganisms, living space and surfaces for soil microbes, and contribute to stabilization of organic matter and storage of organic carbon (OC) in soil. Soil aggregation involves fine roots, organic matter and hyphae of arbuscular mycorrhizal (AM) fungi. Hyphal proliferation is essential for soil aggregation and sequestration of OC in soil. We do not yet have a mechanism to directly quantify the density of hyphae in soil. Organic materials and available phosphorus are two of the major factors that influence fungi in soil. Organic materials are a source of energy for saprotrophic microbes. Fungal hyphae increase in the presence of organic matter. Phosphorus is an important element usually found in ecosystems. The low availability of phosphorus limits the biological activity of microbes. AM fungi benefit plants by delivering phosphorus to the root system. However, the density and the length of hyphae of AM fungi do not appear to be influenced by available phosphorus. A number of indirect methods have been used to visualize distribution of fungi in soil. Reliable analyses of soil are limited because of soil characteristics. Soils are fragile, and fragility limits opportunity for non-destructive analysis. The soil ecosystem is complex. Soil particles are dense and the density obscures the visualization of fungal hyphae. Fungal hyphae are relatively fine and information at the small scale (<250µm) is key to understanding how fungi respond to environmental stimuli. This experiment tested whether organic carbon (starch), phosphorus (K2HPO4) and their mixture influences proliferation of hyphae of AM fungi. Hyphae were quantified in an artificial soil matrix using micro-computer aided tomography. Micro-computer aided tomography provides three dimensional images of hyphal ramification through electron lucent materials and enables the visualization and quantification of hyphae. Starch and the mixture of starch plus K2HPO4, stimulated hyphal proliferation, while K2HPO4 alone did not change the density of hyphae. The images also indicate that fungal hyphae attached to the surfaces of the particles rather than grow through the spaces between them. The capacity to quantify hyphae in three-dimensional space allows a wide range of questions to now be addressed. Apart from studying mechanisms of carbon turnover, more complex processes may now be considered. Soil is commonly thought of as a black box. That black box is now a shade of grey.

Inhibitory effects of Atractylodis lanceae rhizoma and Poria on collagen- or thromboxane A2-induced aggregation in rabbit platelets.

PubMed

Nasu, Yuiko; Iwashita, Masaya; Saito, Masaki; Fushiya, Shinji; Nakahata, Norimichi

2009-05-01

Kami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation.

Studies on a lipopolysaccharide-protein complex from Yersinia pseudotuberculosis. 1 isolation and characterization.

PubMed

Solov'eva, T F; Yermak, I M; Bondarenko, O D; Frolova, G M; Ovodov, Y S

1979-01-01

A comparative study of various procedures of a lipopolysaccharide-protein complex (LPPC) from Yersinia pseudotuberculosis was carried out. The materials obtained were fractionated by molecular-sieve chromatography on Sepharose 2B resulting in highly aggregated complexes with antigen activity. LPPC aggregates dissociated in the presence of sodium dodecylsulphate (SDS) and urea. The chemical composition and serologic properties of fractions obtained are under consideration. The protein component of the complex consists of two major polypeptides (molecular weights--45,000 and 20,000) and some minor ones. The LPS component appeared to give 2--3 narrow bands in gel under conditions of SDS-polyacrylamide gel electrophoresis. It is suggested that such fractionation is caused by LPS association-dissociation in the course of electrophoresis.

Partitioning of uranyl between ferrihydrite and humic substances at acidic and circum-neutral pH

NASA Astrophysics Data System (ADS)

Dublet, Gabrielle; Lezama Pacheco, Juan; Bargar, John R.; Fendorf, Scott; Kumar, Naresh; Lowry, Gregory V.; Brown, Gordon E.

2017-10-01

As part of a larger study of the reactivity and mobility of uranyl (U(VI)O22+) cations in subsurface environments containing natural organic matter (NOM) and hydrous ferric oxides, we have examined the effect of reference humic and fulvic substances on the sorption of uranyl on 2-line ferrihydrite (Fh), a common, naturally occurring nano-Fe(III)-hydroxide. Uranyl was reacted with Fh at pH 4.6 and 7.0 in the presence and absence of Elliott Soil Humic Acid (ESHA) (0-835 ppm) or Suwanee River Fulvic Acid (SRFA) (0-955 ppm). No evidence was found for reduction of uranyl by either form of NOM after 24 h of exposure. The following three size fractions were considered in this study: (1) ≥0.2 μm (Fh-NOM aggregates), (2) 0.02-0.2 μm (dispersed Fh nanoparticles and NOM macro-molecules), and (3) <0.02 μm (dissolved). The extent to which U(VI) is sorbed in aggregates or dispersed as colloids was assessed by comparing U, Fe, and NOM concentrations in these three size fractions. Partitioning of uranyl between Fh and NOM was determined in size fraction (1) using X-ray absorption spectroscopy (XAS). Uranyl sorption on Fh-NOM aggregates was affected by the presence of NOM in different ways depending on pH and type of NOM (ESHA vs. SRFA). The presence of ESHA in the uranyl-Fh-NOM ternary system at pH 4.6 enhanced uranyl uptake more than the presence of SRFA. In contrast, neither form of NOM affected uranyl sorption at pH 7.0 over most of the NOM concentration range examined (0-500 ppm); at the highest NOM concentrations (500-955 ppm) uranyl uptake in the aggregates was slightly inhibited at pH 7.0, which is interpreted as being due to the dispersion of Fh aggregates. XAS at the U LIII-edge was used to characterize molecular-level changes in uranyl complexation as a result of sorption to the Fh-NOM aggregates. In the absence of NOM, uranyl formed dominantly inner-sphere, mononuclear, bidentate sorption complexes on Fh. However, when NOM concentration was increased at pH 4.6, the proportion of uranyl-Fh inner-sphere sorption complexes decreased relative to uranyl-ESHA or uranyl-SRFA complexes, which comprised up to ∼60% of the total uranyl in the systems studied. At pH 7.0, uranyl-NOM complexes were also present in the Fh-NOM aggregates in the concentration ranges of ESHA or SRFA considered; however, the proportion of these complexes was smaller at pH 7.0 than at pH 4.6 and did not increase significantly with increasing NOM concentration.

Exploring the early steps of amyloid peptide aggregation by computers.

PubMed

Mousseau, Normand; Derreumaux, Philippe

2005-11-01

The assembly of normally soluble proteins into amyloid fibrils is a hallmark of neurodegenerative diseases. Because protein aggregation is very complex, involving a variety of oligomeric metastable intermediates, the detailed aggregation paths and structural characterization of the intermediates remain to be determined. Yet, there is strong evidence that these oligomers, which form early in the process of fibrillogenesis, are cytotoxic. In this paper, we review our current understanding of the underlying factors that promote the aggregation of peptides into amyloid fibrils. We focus here on the structural and dynamic aspects of the aggregation as observed in state-of-the-art computer simulations of amyloid-forming peptides with an emphasis on the activation-relaxation technique.

Quantitative analysis of intrinsic and extrinsic factors in the aggregation mechanism of Alzheimer-associated Aβ-peptide

NASA Astrophysics Data System (ADS)

Meisl, Georg; Yang, Xiaoting; Frohm, Birgitta; Knowles, Tuomas P. J.; Linse, Sara

2016-01-01

Disease related mutations and environmental factors are key determinants of the aggregation mechanism of the amyloid-β peptide implicated in Alzheimer's disease. Here we present an approach to investigate these factors through acquisition of highly reproducible data and global kinetic analysis to determine the mechanistic influence of intrinsic and extrinsic factors on the Aβ aggregation network. This allows us to translate the shift in macroscopic aggregation behaviour into effects on the individual underlying microscopic steps. We apply this work-flow to the disease-associated Aβ42-A2V variant, and to a variation in pH as examples of an intrinsic and an extrinsic perturbation. In both cases, our data reveal a shift towards a mechanism in which a larger fraction of the reactive flux goes via a pathway that generates potentially toxic oligomeric species in a fibril-catalyzed reaction. This is in agreement with the finding that Aβ42-A2V leads to early-onset Alzheimer’s disease and enhances neurotoxicity.

Mechanisms and Kinetics of Amyloid Aggregation Investigated by a Phenomenological Coarse-Grained Model

NASA Astrophysics Data System (ADS)

Magno, Andrea; Pellarin, Riccardo; Caflisch, Amedeo

Amyloid fibrils are ordered polypeptide aggregates that have been implicated in several neurodegenerative pathologies, such as Alzheimer's, Parkinson's, Huntington's, and prion diseases, [1, 2] and, more recently, also in biological functionalities. [3, 4, 5] These findings have paved the way for a wide range of experimental and computational studies aimed at understanding the details of the fibril-formation mechanism. Computer simulations using low-resolution models, which employ a simplified representation of protein geometry and energetics, have provided insights into the basic physical principles underlying protein aggregation in general [6, 7, 8] and ordered amyloid aggregation. [9, 10, 11, 12, 13, 14, 15] For example, Dokholyan and coworkers have used the Discrete Molecular Dynamics method [16, 17] to shed light on the mechanisms of protein oligomerization [18] and the conformational changes that take place in proteins before the aggregation onset. [19, 20] One challenging observation, which is difficult to observe by computer simulations, is the wide range of aggregation scenarios emerging from a variety of biophysical measurements. [21, 22] Atomistic models have been employed to study the conformational space of amyloidogenic polypeptides in the monomeric state, [23, 24, 25] the very initial steps of amyloid formation, [26, 27, 28, 29, 30, 31, 32] and the structural stability of fibril models. [33, 34, 35) However, all-atom simulations of the kinetics of fibril formation are beyond what can be done with modern computers.

Corrosion Behavior of Steel Reinforcement in Concrete with Recycled Aggregates, Fly Ash and Spent Cracking Catalyst

PubMed Central

Gurdián, Hebé; García-Alcocel, Eva; Baeza-Brotons, Francisco; Garcés, Pedro; Zornoza, Emilio

2014-01-01

The main strategy to reduce the environmental impact of the concrete industry is to reuse the waste materials. This research has considered the combination of cement replacement by industrial by-products, and natural coarse aggregate substitution by recycled aggregate. The aim is to evaluate the behavior of concretes with a reduced impact on the environment by replacing a 50% of cement by industrial by-products (15% of spent fluid catalytic cracking catalyst and 35% of fly ash) and a 100% of natural coarse aggregate by recycled aggregate. The concretes prepared according to these considerations have been tested in terms of mechanical strengths and the protection offered against steel reinforcement corrosion under carbonation attack and chloride-contaminated environments. The proposed concrete combinations reduced the mechanical performance of concretes in terms of elastic modulus, compressive strength, and flexural strength. In addition, an increase in open porosity due to the presence of recycled aggregate was observed, which is coherent with the changes observed in mechanical tests. Regarding corrosion tests, no significant differences were observed in the case of the resistance of these types of concretes under a natural chloride attack. In the case of carbonation attack, although all concretes did not stand the highly aggressive conditions, those concretes with cement replacement behaved worse than Portland cement concretes. PMID:28788613

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollesch, N.; Dale, V. H.

In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study ofmore » aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.« less

Evaluate the contribution of the mixture components on the longevity and performance of FC-5 : [summary].

DOT National Transportation Integrated Search

2014-05-01

At its most basic, an asphalt mixture is asphalt : binder and crushed stone aggregate. This : seemingly simple mixture is very complex; method : of preparation and application, additives, and : aggregate type all influence the quality and : durabilit...

A molecular rotor based ratiometric sensor for basic amino acids.

PubMed

Pettiwala, Aafrin M; Singh, Prabhat K

2018-01-05

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Binding of heavy metal ions in aggregates of microbial cells, EPS and biogenic iron minerals measured in-situ using metal- and glycoconjugates-specific fluorophores

NASA Astrophysics Data System (ADS)

Hao, Likai; Guo, Yuan; Byrne, James M.; Zeitvogel, Fabian; Schmid, Gregor; Ingino, Pablo; Li, Jianli; Neu, Thomas R.; Swanner, Elizabeth D.; Kappler, Andreas; Obst, Martin

2016-05-01

Aggregates consisting of bacterial cells, extracellular polymeric substances (EPS) and Fe(III) minerals formed by Fe(II)-oxidizing bacteria are common at bulk or microscale chemical interfaces where Fe cycling occurs. The high sorption capacity and binding capacity of cells, EPS, and minerals controls the mobility and fate of heavy metals. However, it remains unclear to which of these component(s) the metals will bind in complex aggregates. To clarify this question, the present study focuses on 3D mapping of heavy metals sorbed to cells, glycoconjugates that comprise the majority of EPS constituents, and Fe(III) mineral aggregates formed by the phototrophic Fe(II)-oxidizing bacteria Rhodobacter ferrooxidans SW2 using confocal laser scanning microscopy (CLSM) in combination with metal- and glycoconjugates-specific fluorophores. The present study evaluated the influence of glycoconjugates, microbial cell surfaces, and (biogenic) Fe(III) minerals, and the availability of ferrous and ferric iron on heavy metal sorption. Analyses in this study provide detailed knowledge on the spatial distribution of metal ions in the aggregates at the sub-μm scale, which is essential to understand the underlying mechanisms of microbe-mineral-metal interactions. The heavy metals (Au3+, Cd2+, Cr3+, CrO42-, Cu2+, Hg2+, Ni2+, Pd2+, tributyltin (TBT) and Zn2+) were found mainly sorbed to cell surfaces, present within the glycoconjugates matrix, and bound to the mineral surfaces, but not incorporated into the biogenic Fe(III) minerals. Statistical analysis revealed that all ten heavy metals tested showed relatively similar sorption behavior that was affected by the presence of sorbed ferrous and ferric iron. Results in this study showed that in addition to the mineral surfaces, both bacterial cell surfaces and the glycoconjugates provided most of sorption sites for heavy metals. Simultaneously, ferrous and ferric iron ions competed with the heavy metals for sorption sites on the organic compounds. In summary, the information obtained by the present approach using a microbial model system provides important information to better understand the interactions between heavy metals and biofilms, and microbially formed Fe(III) minerals and heavy metals in complex natural environments.

Aggregate structure and effect of phthalic anhydride modified soy protein on the mechanical properties of styrene-butadiene copolymer

USDA-ARS?s Scientific Manuscript database

The aggregate structure of phthalic anhydride (PA) modified soy protein isolate (SPI) was investigated by estimating its fractal dimension from the equilibrated dynamic strain sweep experiments. The estimated fractal dimensions of the filler aggregates were less than 2, indicating that these partic...

α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane.

PubMed

Monsellier, Elodie; Bousset, Luc; Melki, Ronald

2016-01-13

Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain.

α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane

PubMed Central

Monsellier, Elodie; Bousset, Luc; Melki, Ronald

2016-01-01

Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain. PMID:26757959

A Two-Dimensional Numerical Investigation of Transport of Malaria-Infected Red Blood Cells in Stenotic Microchannels

PubMed Central

Tao, Yong; Rongin, Uwitije; Xing, Zhongwen

2016-01-01

The malaria-infected red blood cells experience a significant decrease in cell deformability and increase in cell membrane adhesion. Blood hemodynamics in microvessels is significantly affected by the alteration of the mechanical property as well as the aggregation of parasitized red blood cells. In this study, we aim to numerically study the connection between cell-level mechanobiological properties of human red blood cells and related malaria disease state by investigating the transport of multiple red blood cell aggregates passing through microchannels with symmetric stenosis. Effects of stenosis magnitude, aggregation strength, and cell deformability on cell rheology and flow characteristics were studied by a two-dimensional model using the fictitious domain-immersed boundary method. The results indicated that the motion and dissociation of red blood cell aggregates were influenced by these factors and the flow resistance increases with the increase of aggregating strength and cell stiffness. Further, the roughness of the velocity profile was enhanced by cell aggregation, which considerably affected the blood flow characteristics. The study may assist us in understanding cellular-level mechanisms in disease development. PMID:28105411

Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism

PubMed Central

Morales-Scheihing, Diego; Salvadores, Natalia; Moreno-Gonzalez, Ines; Gonzalez, Cesar; Shahnawaz, Mohammad

2017-01-01

Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases. PMID:28765400

The mechanism of erythrocyte sedimentation. Part 1: Channeling in sedimenting blood.

PubMed

Pribush, A; Meyerstein, D; Meyerstein, N

2010-01-01

Despite extensive efforts to elucidate the mechanism of erythrocyte sedimentation, the understanding of this mechanism still remains obscure. In attempt to clarify this issue, we studied the effect of hematocrit (Hct) on the complex admittance of quiescent blood measured at different axial positions of the 2 mm x 2 mm cross-section chambers. It was found that after the aggregation process is completed, the admittance reveals delayed changes caused by the formation of cell-free zones within the settling dispersed phase. The delay time (tau(d)) correlates positively with Hct and the distance between the axial position where measurements were performed and the bottom and is unaffected by the gravitational load. These findings and literature reports for colloidal gels suggest that erythrocytes in aggregating media form a network followed by the formation of plasma channels within it. The cell-free zones form initially near the bottom and then propagate toward the top until they reach the plasma/blood interface. These channels increase the permeability of a network and, as a result, accelerate the sedimentation velocity. The energy of the flow field in channels is sufficiently strong to erode their walls. The upward movement of network fragments in channels is manifested by erratic fluctuations of the conductivity. The main conclusion, which may be drawn from the results of this study, is that the phase separation of blood is associated with the formation of plasma channels within the sedimenting dispersed phase.

Identifying Cu( ii )–amyloid peptide binding intermediates in the early stages of aggregation by resonance Raman spectroscopy: a simulation study

DOE PAGES

Ren, Hao; Zhang, Yu; Guo, Sibei; ...

2017-10-31

The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(II)–Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(II) binding are not well understood. Two Cu(II)–Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values. By using ab initio simulations for the spontaneous resonance Ramanmore » and time domain stimulated resonance Raman spectroscopy signals, we obtained the characteristic Raman vibronic features of each complex. Finally, these signals contain rich structural information with high temporal resolution, enabling the characterization of transient states during the fast Cu–Aβ binding and interconversion processes.« less

Using complexation for the microencapsulation of nisin in biopolymer matrices by spray-drying.

PubMed

Ben Amara, Chedia; Kim, Lanhee; Oulahal, Nadia; Degraeve, Pascal; Gharsallaoui, Adem

2017-12-01

The aim of this study is to investigate the potential of complexation to encapsulate nisin (5g/L concentration) using spray-drying technique and to evaluate how complexation with pectin or alginate (2g/L concentration) can preserve nisin structure and antimicrobial activity. Spray-drying of nisin-low methoxyl pectin or nisin-alginate electrostatic complexes has led to the microencapsulation of the peptide in different networks that were highly influenced by the polysaccharide type. Turbidity and particle size measurements indicated that while spray-drying promoted the aggregation of nisin-pectin complexes, it favored the dissociation of nisin-alginate aggregates to form individual complexes. Structural changes of nisin induced by complexation with pectin or alginate and spray-drying were studied by using UV-Vis absorption and fluorescence spectroscopy. The results showed that complexation with pectin or alginate preserved nisin structure as well as its antimicrobial activity during spray-drying. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colloidal Aggregate Structure under Shear by USANS

NASA Astrophysics Data System (ADS)

Chatterjee, Tirtha; van Dyk, Antony K.; Ginzburg, Valeriy V.; Nakatani, Alan I.

2015-03-01

Paints are complex formulations of polymeric binders, inorganic pigments, dispersants, surfactants, colorants, rheology modifiers, and other additives. A commercially successful paint exhibits a desired viscosity profile over a wide shear rate range from 10-5 s-1 for settling to >104 s-1 for rolling, and spray applications. Understanding paint formulation structure is critical as it governs the paint viscosity profile. However, probing paint formulation structure under shear is a challenging task due to the formulation complexity containing structures with different hierarchical length scales and their alterations under the influence of an external flow field. In this work mesoscale structures of paint formulations under shear are investigated using Ultra Small-Angle Neutron Scattering (rheo-USANS). Contrast match conditions were utilized to independently probe the structure of latex binder particle aggregates and the TiO2 pigment particle aggregates. Rheo-USANS data revealed that the aggregates are fractal in nature and their self-similarity dimensions and correlations lengths depend on the chemistry of the binder particles, the type of rheology modifier present and the shear stress imposed upon the formulation. These results can be explained in the framework of diffusion and reaction limited transient aggregates structure evolution under simple shear.

Salt-induced aggregation of lysozyme: Implications for crystal growth

NASA Technical Reports Server (NTRS)

Wilson, Lori J.

1994-01-01

Crystallization of proteins is a prerequisite for structural analysis by x-ray crystallography. While improvements in protein crystals have been obtained in microgravity onboard the U.S. Space Shuttle, attempts to improve the crystal growth process both on the ground and in space have been limited by our lack of understanding of the mechanisms involved. Almost all proteins are crystallized with the aid of a precipitating agent. Many of the common precipitating agents are inorganic salts. An understanding of the role of salts on the aggregation of protein monomers is the key to the elucidation of the mechanisms involved in protein crystallization. In order for crystallization to occur individual molecules must self-associate into aggregates. Detection and characterization of aggregates in supersaturated protein solutions is the first step in understanding salt-induced crystallization.

Evaluation of steel slag coarse aggregate in hot mix asphalt concrete.

PubMed

Ahmedzade, Perviz; Sengoz, Burak

2009-06-15

This paper presents the influences of the utilization of steel slag as a coarse aggregate on the properties of hot mix asphalt. Four different asphalt mixtures containing two types of asphalt cement (AC-5; AC-10) and coarse aggregate (limestone; steel slag) were used to prepare Marshall specimens and to determine optimum bitumen content. Mechanical characteristics of all mixtures were evaluated by Marshall stability, indirect tensile stiffness modulus, creep stiffness, and indirect tensile strength tests. The electrical sensitivity of the specimens were also investigated in accordance with ASTM D257-91. It was observed that steel slag used as a coarse aggregate improved the mechanical properties of asphalt mixtures. Moreover, volume resistivity values demonstrated that the electrical conductivity of steel slag mixtures were better than that of limestone mixtures.

Study on the Effect of Straw Fiber on the Performance of Volcanic Slag Concrete

NASA Astrophysics Data System (ADS)

Xiao, Li-guang; Liu, Xi-xu

2018-03-01

In this paper, the effects of straw fiber on the working performance, mechanical properties and frost resistance of volcanic slag lightweight aggregate concrete were studied. The experimental results show that the straw fiber is subjected to surface carbonization treatment and mixed into the volcanic slag light aggregate concrete. The flexural strength and fracture pressure ratio of volcanic slag lightweight aggregate concrete are improved obviously Improved volcanic slag lightweight aggregate concrete brittleness improves toughness. Carbonized straw fiber greatly improves the frost resistance of volcanic slag lightweight aggregate concrete. So that the volcanic slag light aggregate concrete freeze-thaw cycle can reach 300 times.

Mechanical and Physical Properties of Hydrophobized Lightweight Aggregate Concrete with Sewage Sludge.

PubMed

Suchorab, Zbigniew; Barnat-Hunek, Danuta; Franus, Małgorzata; Łagód, Grzegorz

2016-04-27

This article is focused on lightweight aggregate-concrete modified by municipal sewage sludge and lightweight aggregate-concrete obtained from light aggregates. The article presents laboratory examinations of material physical parameters. Water absorptivity of the examined material was decreased by the admixture of water emulsion of reactive polysiloxanes. Water transport properties were determined using Time Domain Reflectometry, an indirect technique for moisture detection in porous media. Together with basic physical parameters, the heat conductivity coefficient λ was determined for both types of lightweight aggregate-concrete. Analysis of moisture and heat properties of the examined materials confirmed the usefulness of light aggregates supplemented with sewage sludge for prospective production.

The Structure of Intrinsically Disordered Peptides Implicated in Amyloid Diseases: Insights from Fully Atomistic Simulations

NASA Astrophysics Data System (ADS)

Wu, Chun; Shea, Joan-Emma

Protein aggregation involves the self-assembly of proteins into large β-sheet-rich complexes. This process can be the result of aberrant protein folding and lead to "amyloidosis," a condition characterized by deposits of protein aggregates known as amyloids on various organs of the body [1]. Amyloid-related diseases include, among others, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and type II diabetes [2, 3, 4]. In other instances, however, protein aggregation is not a pathological process, but rather a functional one, with aggregates serving as structural scaffolds in a number of organisms [5].

Origin of long-lived oscillations in 2D-spectra of a quantum vibronic model: Electronic versus vibrational coherence

NASA Astrophysics Data System (ADS)

Plenio, M. B.; Almeida, J.; Huelga, S. F.

2013-12-01

We demonstrate that the coupling of excitonic and vibrational motion in biological complexes can provide mechanisms to explain the long-lived oscillations that have been obtained in nonlinear spectroscopic signals of different photosynthetic pigment protein complexes and we discuss the contributions of excitonic versus purely vibrational components to these oscillatory features. Considering a dimer model coupled to a structured spectral density we exemplify the fundamental aspects of the electron-phonon dynamics, and by analyzing separately the different contributions to the nonlinear signal, we show that for realistic parameter regimes purely electronic coherence is of the same order as purely vibrational coherence in the electronic ground state. Moreover, we demonstrate how the latter relies upon the excitonic interaction to manifest. These results link recently proposed microscopic, non-equilibrium mechanisms to support long lived coherence at ambient temperatures with actual experimental observations of oscillatory behaviour using 2D photon echo techniques to corroborate the fundamental importance of the interplay of electronic and vibrational degrees of freedom in the dynamics of light harvesting aggregates.

Impact of lipid rafts on the T -cell-receptor and peptide-major-histocompatibility-complex interactions under different measurement conditions

NASA Astrophysics Data System (ADS)

Li, Long; Xu, Guang-Kui; Song, Fan

2017-01-01

The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation. This finding may provide an alternative insight into the mechanism of T-cell activation triggered by very low densities of pMHC. In the case of cell-substrate adhesion, our results indicate that the loss of lateral mobility of the proteins on the solid substrate leads to the inhibitory effect of lipid rafts on TCR-pMHC interactions. Our findings help to understand why different experimental methods for measuring the impact of lipid rafts on the receptor-ligand interactions have led to contradictory conclusions.

Roles of Autophagy in MPP+-Induced Neurotoxicity In Vivo: The Involvement of Mitochondria and α-Synuclein Aggregation

PubMed Central

Lin, Ming-Wei; Lei, Yen-Ping; Lin, Anya Maan-yuh

2014-01-01

Macroautophagy (also known as autophagy) is an intracellular self-eating mechanism and has been proposed as both neuroprotective and neurodestructive in the central nervous system (CNS) neurodegenerative diseases. In the present study, the role of autophagy involving mitochondria and α-synuclein was investigated in MPP+ (1-methyl-4-phenylpyridinium)-induced oxidative injury in chloral hydrate-anesthetized rats in vivo. The oxidative mechanism underlying MPP+-induced neurotoxicity was identified by elevated lipid peroxidation and heme oxygenase-1 levels, a redox-regulated protein in MPP+-infused substantia nigra (SN). At the same time, MPP+ significantly increased LC3-II levels, a hallmark protein of autophagy. To block MPP+-induced autophagy in rat brain, Atg7siRNA was intranigrally infused 4 d prior to MPP+ infusion. Western blot assay showed that in vivo Atg7siRNA transfection not only reduced Atg7 levels in the MPP+-infused SN but attenuated MPP+-induced elevation in LC3-II levels, activation of caspase 9 and reduction in tyrosine hydroxylase levels, indicating that autophagy is pro-death. The immunostaining study demonstrated co-localization of LC3 and succinate dehydrogenase (a mitochondrial complex II) as well as LC3 and α-synuclein, suggesting that autophagy may engulf mitochondria and α-synuclein. Indeed, in vivo Atg7siRNA transfection mitigated MPP+-induced reduction in cytochrome c oxidase. In addition, MPP+-induced autophagy differentially altered the α-synuclein aggregates in the infused SN. In conclusion, autophagy plays a prodeath role in the MPP+-induced oxidative injury by sequestering mitochondria in the rat brain. Moreover, our data suggest that the benefits of autophagy depend on the levels of α-synuclein aggregates in the nigrostriatal dopaminergic system of the rat brain. PMID:24646838

The single scattering properties of soot aggregates with concentric core-shell spherical monomers

NASA Astrophysics Data System (ADS)

Wu, Yu; Cheng, Tianhai; Gu, Xingfa; Zheng, Lijuan; Chen, Hao; Xu, Hui

2014-03-01

Anthropogenic soot aerosols are shown as complex, fractal-like aggregated structures with high light absorption efficiency. In atmospheric environment, soot monomers may tend to acquire a weakly absorbing coating, such as an organic coating, which introduces further complexity to the optical properties of the aggregates. The single scattering properties of soot aggregates can be significantly influenced by the coated status of these kinds of aerosols. In this article, the monomers of fractal soot aggregates are modelled as semi-external mixtures (physical contact) with constant radius of soot core and variable sizes of the coating for specific soot volume fractions. The single scattering properties of these coated soot particles, such as phase function, the cross sections of extinction and absorption, single scattering albedo (SSA) and asymmetry parameter (ASY), are calculated using the numerically exact superposition T-matrix method. The random-orientation averaging results have shown that the single scattering properties of these coated soot aggregates are significantly different from the single volume-equivalent core-shell sphere approximation using the Mie theory and the homogeneous aggregates with uncoated monomers using the effective medium theory, such as Maxwell-Garnett and Bruggemann approximations, which overestimate backscattering of coated soot. It is found that the SSA and cross sections of extinction and absorption are increased for soot aggregates with thicker weakly absorbing coating on the monomers. Especially, the SSA values of these simulated aggregates with less soot core volume fractions are remarkably (~50% for core volume fraction of soot aggregates of 0.5, ~100% for a core volume fraction of 0.2, at 0.67 μm) larger than for uncoated soot particles without consideration of coating. Moreover, the cross sections of extinction and absorption are underestimated by the computation of equivalent homogeneous fractal aggregate approximation (within 5% for the T-matrix method and 10-25% for the Rayleigh-Debye-Gans approximation due to different soot volume fractions). Further understanding of the optical properties of these coated soot aggregates would be helpful for both environment monitoring and climate studies.

Polyion-induced aggregation of oppositely charged liposomes and charged colloidal particles: the many facets of complex formation in low-density colloidal systems.

PubMed

Cametti, C

2008-10-01

This review focusses on recent developments in the experimental study of polyion-induced charged colloidal particle aggregation, with particular emphasis on the formation of cationic liposome clusters induced by the addition of anionic adsorbing polyions. These structures can be considered, under certain points of view, a new class of colloidal systems, with intriguing properties that opens interesting and promising new opportunities in various biotechnological applications. Lipidic structures of different morphologies and different structural complexities interacting with oppositely charged polyions give rise to a rich variety of self-assembled structures that present various orders of hierarchy in the sense that, starting from a basic level, for example a lipid bilayer, they arrange themselves into superstructures as, for example, multilamellar stacks or liquid-crystalline structures. These structures can be roughly divided into two classes according to the fact that the elementary structure, involved in building a more complex one, keeps or does not keeps its basic arrangement. To the first one, belong those aggregates composed by single structures that maintain their integrity, for example, lipidic vesicles assembled together by an appropriate external agent. The second one encompasses structures that do not resemble the ones of the original objects which form them, but, conversely, derive from a deep restructuring and rearrangement process, where the original morphology of the initial constitutive elements is completely lost. In this review, I will only briefly touch on higher level hierarchy structures and I will focus on the assembling processes involving preformed lipid bilayer vesicles that organize themselves into clusters, the process being induced by the adsorption of oppositely charged polyions. The scientific interest in polyion-induced liposome aggregates is two-fold. On the one hand, in soft-matter physics, they represent an interesting colloidal system, governed by a balance between long-range electrostatic repulsion and short-range attraction, resulting in relatively large, equilibrium clusters, whose size and overall charge can be continuously tunable by simple environmental parameters. These structures present a variety of behaviors with a not yet completely understood phenomenology. On the other hand, the resulting structures possess some peculiar properties that justify their employment as drug delivery systems. Bio-compatibility, stability and ability to deliver various bio-active molecules and, moreover, their environmental responsiveness make liposome-based clusters a versatile carrier, with possibility of efficient targeting to different organs and tissues. Among the different structures made possible by the aggregating mechanism (cationic particles stuck together by anionic polyions or conversely anionic particles stuck together by cationic polyions), I will review the main experimental evidences for the existence of cationic liposome clusters. Especial attention is paid to our own work, mainly aimed at the characterization of these novel structures from a physical point of view.

Metamodeling Techniques to Aid in the Aggregation Process of Large Hierarchical Simulation Models

DTIC Science & Technology

2008-08-01

Level Outputs Campaign Level Model Campaign Level Outputs Aggregation Metamodeling Complexity (Spatial, Temporal, etc.) Others? Apply VRT (type......reduction, are called variance reduction techniques ( VRT ) [Law, 2006]. The implementation of some type of VRT can prove to be a very valuable tool

Efficient clustering aggregation based on data fragments.

PubMed

Wu, Ou; Hu, Weiming; Maybank, Stephen J; Zhu, Mingliang; Li, Bing

2012-06-01

Clustering aggregation, known as clustering ensembles, has emerged as a powerful technique for combining different clustering results to obtain a single better clustering. Existing clustering aggregation algorithms are applied directly to data points, in what is referred to as the point-based approach. The algorithms are inefficient if the number of data points is large. We define an efficient approach for clustering aggregation based on data fragments. In this fragment-based approach, a data fragment is any subset of the data that is not split by any of the clustering results. To establish the theoretical bases of the proposed approach, we prove that clustering aggregation can be performed directly on data fragments under two widely used goodness measures for clustering aggregation taken from the literature. Three new clustering aggregation algorithms are described. The experimental results obtained using several public data sets show that the new algorithms have lower computational complexity than three well-known existing point-based clustering aggregation algorithms (Agglomerative, Furthest, and LocalSearch); nevertheless, the new algorithms do not sacrifice the accuracy.

Applications of aggregation theory to sustainability assessment

DOE PAGES

Pollesch, N.; Dale, V. H.

2015-04-01

In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study ofmore » aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.« less

Impact of reduced tillage and organic inputs on aggregate stability and earthworm community in a Breton context in France

NASA Astrophysics Data System (ADS)

Paillat, Louise; Menasseri, Safya; Busnot, Sylvain; Roucaute, Marc; Benard, Yannick; Morvan, Thierry; Pérès, Guénola

2017-04-01

Soil aggregate stability, which refers to the ability of soil aggregates to resist breakdown when disruptive forces are applied (water, wind), is a good indicator of the sensitivity of soil to crusting and erosion and is a relevant indicator for soil stability. Within soil parameters which affect soil stability, organic matter is one of the main important by functioning as bonding agent between mineral soil particles, but soil organisms such as microorganisms and earthworms are also recognized as efficient agents. However the relationship between earthworms, fungal hyphae and aggregation is still unclear. In order to assess the influence of these biological agents on aggregate dynamics, we have combined a field study and a laboratory experiment. On a long term experiment trial in Brittany, SOERE PRO-EFELE, we have studied the effect of reduced tillage (vs. conventional tillage) combined to organic inputs (vs. mineral inputs) on earthworm community and soil stability. Aggregate stability was measured at different perturbations intensities: fast wetting (FW), slow wetting (SW) and mechanical breakdown (MB). This study showed that after 4 years of experiments, reduced tillage and organic inputs enhanced aggregate stability. Earthworms modulated aggregation process: endogeics reduced FW stability (mechanical binding by hyphae) and anecics increased SW stability (aggregate interparticular cohesion and hydrophobicity). Some precisions were provided by the laboratory experiment, using microcosms, which compared casts of the endogeic Aporectodea c. caliginosa (NCCT) and the anecic Lumbricus terrestris (LT). The presumed hyphae fragmentation by endogeics could not be highlight in NCCT casts. Nevertheless, hyphae were more abundant and C content and aggregate stability were higher in LT casts corroborating the positive contribution of anecics to aggregate stability.

Control of electron-lattice interaction in organic nanoclusters

NASA Astrophysics Data System (ADS)

Malyukin, Yu. V.; Gnap, B. A.; Sorokin, A. V.; Yefimova, S. L.

2012-10-01

In this study we demonstrate that the electron-lattice interaction (ELI) could be controlled by changing exciton delocalization length in ordered organic nanoclusters called J-aggregates. Particularly it could be done via the J-aggregates solvate shell manipulation using surfactants. The strong correlation between the J-aggregates luminescence quantum yield and the ELI strength has been reviled that allows us to consider the exciton self-trapping as the main mechanism of the J-aggregates luminescence losses.

The Effects of Different Fine Recycled Concrete Aggregates on the Properties of Mortar

PubMed Central

Fan, Cheng-Chih; Huang, Ran; Hwang, Howard; Chao, Sao-Jeng

2015-01-01

The practical use of recycled concrete aggregate produced by crushing concrete waste reduces the consumption of natural aggregate and the amount of concrete waste that ends up in landfills. This study investigated two methods used in the production of fine recycled concrete aggregate: (1) a method that produces fine as well as coarse aggregate, and (2) a method that produces only fine aggregate. Mortar specimens were tested using a variety of mix proportions to determine how the characteristics of fine recycled concrete aggregate affect the physical and mechanical properties of the resulting mortars. Our results demonstrate the superiority of mortar produced using aggregate produced using the second of the two methods. Nonetheless, far more energy is required to render concrete into fine aggregate than is required to produce coarse as well as fine aggregate simultaneously. Thus, the performance benefits of using only fine recycled concrete aggregate must be balanced against the increased impact on the environment.

Scrutiny of the mechanism of small molecule inhibitor preventing conformational transition of amyloid-β42 monomer: insights from molecular dynamics simulations.

PubMed

Shuaib, Suniba; Goyal, Bhupesh

2018-02-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by loss of intellectual functioning of brain and memory loss. According to amyloid cascade hypothesis, aggregation of amyloid-β 42 (Aβ 42 ) peptide can generate toxic oligomers and their accumulation in the brain is responsible for the onset of AD. In spite of carrying out a large number of experimental studies on inhibition of Aβ 42 aggregation by small molecules, the detailed inhibitory mechanism remains elusive. In the present study, comparable molecular dynamics (MD) simulations were performed to elucidate the inhibitory mechanism of a sulfonamide inhibitor C1 (2,5-dichloro-N-(4-piperidinophenyl)-3-thiophenesulfonamide), reported for its in vitro and in vivo anti-aggregation activity against Aβ 42 . MD simulations reveal that C1 stabilizes native α-helix conformation of Aβ 42 by interacting with key residues in the central helix region (13-26) with hydrogen bonds and π-π interactions. C1 lowers the solvent-accessible surface area of the central hydrophobic core (CHC), KLVFF (16-20), that confirms burial of hydrophobic residues leading to the dominance of helical conformation in the CHC region. The binding free energy analysis with MM-PBSA demonstrates that Ala2, Phe4, Tyr10, Gln15, Lys16, Leu17, Val18, Phe19, Phe20, Glu22, and Met35 contribute maximum to binding free energy (-43.1 kcal/mol) between C1 and Aβ 42 monomer. Overall, MD simulations reveal that C1 inhibits Aβ 42 aggregation by stabilizing native helical conformation and inhibiting the formation of aggregation-prone β-sheet conformation. The present results will shed light on the underlying inhibitory mechanism of small molecules that show potential in vitro anti-aggregation activity against Aβ 42 .

Ultra-Fine Scale Spatially-Integrated Mapping of Habitat and Occupancy Using Structure-From-Motion.

PubMed

McDowall, Philip; Lynch, Heather J

2017-01-01

Organisms respond to and often simultaneously modify their environment. While these interactions are apparent at the landscape extent, the driving mechanisms often occur at very fine spatial scales. Structure-from-Motion (SfM), a computer vision technique, allows the simultaneous mapping of organisms and fine scale habitat, and will greatly improve our understanding of habitat suitability, ecophysiology, and the bi-directional relationship between geomorphology and habitat use. SfM can be used to create high-resolution (centimeter-scale) three-dimensional (3D) habitat models at low cost. These models can capture the abiotic conditions formed by terrain and simultaneously record the position of individual organisms within that terrain. While coloniality is common in seabird species, we have a poor understanding of the extent to which dense breeding aggregations are driven by fine-scale active aggregation or limited suitable habitat. We demonstrate the use of SfM for fine-scale habitat suitability by reconstructing the locations of nests in a gentoo penguin colony and fitting models that explicitly account for conspecific attraction. The resulting digital elevation models (DEMs) are used as covariates in an inhomogeneous hybrid point process model. We find that gentoo penguin nest site selection is a function of the topography of the landscape, but that nests are far more aggregated than would be expected based on terrain alone, suggesting a strong role of behavioral aggregation in driving coloniality in this species. This integrated mapping of organisms and fine scale habitat will greatly improve our understanding of fine-scale habitat suitability, ecophysiology, and the complex bi-directional relationship between geomorphology and habitat use.

Silver nanoparticle aggregation not triggered by an ionic strength mechanism

NASA Astrophysics Data System (ADS)

Botasini, Santiago; Méndez, Eduardo

2013-04-01

The synthesis of stable colloidal solutions of silver nanoparticles is a major goal in the industry to control their fate in aqueous solutions. The present work studies 10-20-nm silver nanoparticle aggregation triggered by the presence of chloride ions. The aggregation process was followed by UV-Vis-NIR spectroscopy and transmission electron microscopy. We found that the mechanism involved differs from the classic explanation of nanoparticle aggregation triggered by an increase in the ionic strength. Moreover, our results give evidence that even when nanoparticles are resistant to an increment of the total amount of ions, the formation of insoluble salts in the vicinity of the nanoparticle is enough to induce the aggregation. The presence of silver chloride around the silver nanoparticles was documented by an X-ray diffraction pattern and electrochemical methods because chloride anions are ubiquitous in real media; this alternative process jeopardized the development of many applications with silver nanoparticles that depend on the use of stable colloids.

Shaken, but not stirred: how vortical flow drives small-scale aggregations of gyrotactic phytoplankton

NASA Astrophysics Data System (ADS)

Barry, Michael; Durham, William; Climent, Eric; Stocker, Roman

2011-11-01

Coastal ocean observations reveal that motile phytoplankton form aggregations at the Kolmogorov scale (mm-cm), whereas non-motile cells do not. We propose a new mechanism for the formation of this small-scale patchiness based on the interplay of turbulence and gyrotactic motility. Counterintuitively, turbulence does not stir a plankton suspension to homogeneity but drives aggregations instead. Through controlled laboratory experiments we show that the alga Heterosigma akashiwo rapidly forms aggregations in a cavity-driven vortical flow that approximates Kolmogorov eddies. Gyrotactic motility is found to be the key ingredient for aggregation, as non-motile cells remain randomly distributed. Observations are in remarkable agreement with a 3D model, and the validity of this mechanism for generating patchiness has been extended to realistic turbulent flows using Direct Numerical Simulations. Because small-scale patchiness influences rates of predation, sexual reproduction, infection, and nutrient competition, this result indicates that gyrotactic motility can profoundly affect phytoplankton ecology.

Fresh and mechanical properties of self-compacting concrete with coarse aggregate replacement using Waste of Oil Palm Shell

NASA Astrophysics Data System (ADS)

Prayuda, Hakas; Saleh, Fadillawaty; Ilham Maulana, Taufiq; Monika, Fanny

2018-05-01

Self-compacting Concrete (SCC) is a real innovation that can solidify itself without the help of tools to ease field practice. In its implementation, SCC can use alternative materials to reduce waste, such as Oil Palm Shell (OPS). In this research, OPS used as a replacement of crushed stone as the main coarse aggregate. The concrete mixture used consists of cement, sand, crushed stone, OPS as a variation of aggregate substitutes, palm oil fuel ash, and superplasticizer. OPS used were variated with 0%, 5%, 10%, 25% and 50% of crushed stone aggregate weight with age up to 28 days. Tests were conducted on fresh and mechanical properties. From the results, it is known that replacement of aggregate using OPS meets fresh properties criteria and although the compressive strength of OPS concrete mixture is lower than normal SCC, OPS still can be an alternative in making SCC and reducing palm oil industrial waste.

Aeolian comminution experiments revealing surprising sandball mineral aggregates

NASA Astrophysics Data System (ADS)

Nørnberg, P.; Bak, E.; Finster, K.; Gunnlaugsson, H. P.; Iversen, J. J.; Jensen, S. Knak; Merrison, J. P.

2014-06-01

We have undertaken a set of wind erosion experiments on a simple and well defined mineral, quartz. In these experiments wind action is simulated by end over end tumbling of quartz grains in a sealed quartz flask. The tumbling induces collisions among the quartz grains and the walls of the flask. This process simulates wind action impact speed of ∼1.2 m/s. After several months of tumbling we observed the formation of a large number of spherical sand aggregates, which resemble small snowballs under optical microscopy. Upon mechanical load the aggregates are seen to be more elastic than quartz and their mechanical strength is comparable, though slightly lower than that of sintered silica aerogels. Aggregates of this kind have not been reported from field sites or from closed circulation systems. However, sparse occurrence might explain this, or in nature the concentration of the aggregate building particles is so low that they never meet and just appear as the most fine grained tail of the sediment particle size distribution.

Quality assessment for recycling aggregates from construction and demolition waste: An image-based approach for particle size estimation.

PubMed

Di Maria, Francesco; Bianconi, Francesco; Micale, Caterina; Baglioni, Stefano; Marionni, Moreno

2016-02-01

The size distribution of aggregates has direct and important effects on fundamental properties of construction materials such as workability, strength and durability. The size distribution of aggregates from construction and demolition waste (C&D) is one of the parameters which determine the degree of recyclability and therefore the quality of such materials. Unfortunately, standard methods like sieving or laser diffraction can be either very time consuming (sieving) or possible only in laboratory conditions (laser diffraction). As an alternative we propose and evaluate the use of image analysis to estimate the size distribution of aggregates from C&D in a fast yet accurate manner. The effectiveness of the procedure was tested on aggregates generated by an existing C&D mechanical treatment plant. Experimental comparison with manual sieving showed agreement in the range 81-85%. The proposed technique demonstrated potential for being used on on-line systems within mechanical treatment plants of C&D. Copyright © 2015 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Copuroglu, Oguzhan, E-mail: O.Copuroglu@CiTG.TUDelft.NL; Andic-Cakir, Ozge; Broekmans, Maarten A.T.M.

In this paper, the alkali-silica reaction performance of a basalt rock from western Anatolia, Turkey is reported. It is observed that the rock causes severe gel formation in the concrete microbar test. It appears that the main source of expansion is the reactive glassy phase of the basalt matrix having approximately 70% of SiO{sub 2}. The study presents the microstructural characteristics of unreacted and reacted basalt aggregate by optical and electron microscopy and discusses the possible reaction mechanism. Microstructural analysis revealed that the dissolution of silica is overwhelming in the matrix of the basalt and it eventually generates four consequences:more » (1) Formation of alkali-silica reaction gel at the aggregate perimeter, (2) increased porosity and permeability of the basalt matrix, (3) reduction of mechanical properties of the aggregate and (4) additional gel formation within the aggregate. It is concluded that the basalt rock is highly prone to alkali-silica reaction. As an aggregate, this rock is not suitable for concrete production.« less

Dis-aggregation of an insoluble porphyrin in a calixarene matrix: characterization of aggregate modes by extended dipole model.

PubMed

de Miguel, Gustavo; Martín-Romero, María T; Pedrosa, José M; Muñoz, Eulogia; Pérez-Morales, Marta; Richardson, Tim H; Camacho, Luis

2008-03-21

In this paper, the different aggregation modes of a water-insoluble porphyrin (EHO) mixed with an amphiphilic calix[8]arene (C8A), at the air-water interface and in Langmuir-Blodgett (LB) film form, are analyzed as a function of the mixed composition. The strategy used to control the EHO aggregation has consisted of preparing mixed thin films containing EHO and C8A, in different ratios, at the air-water interface. Therefore, the increase of the C8A molar ratio in the mixed film diminishes the aggregation of the EHO molecules, although such an effect must be exclusively related to the dilution of the porphyrin. The reflection spectra of the mixed C8A-EHO films registered at the air-water interface, show a complex Soret band exhibiting splitting, hypochromicity and broadening features. Also, during the transfer process at high surface pressure, it has been shown that the EHO molecules are ejected from the C8A monolayer and only a fraction of porphyrin is transferred to the solid support, in spite of a complete transfer for the C8A matrix. The complex structure of the reflection spectra at the air-water interface, as well as the polarization dependence of the absorption spectra for the mixed LB films, indicate the existence of four different arrangements for the EHO hosted in the C8A matrix. The aggregate formation is governed by two factors: the attraction between the porphyrin rings which minimizes their separation, and the alkyl chain interactions, that is, hydrophobic effect and/or steric hindrance which determine and restrict the possible aggregation structures. By using the extended dipole model, the assignment of the spectral peaks observed to different EHO aggregates is shown.

Alkoxy bridged binuclear rhenium (I) complexes as a potential sensor for β-amyloid aggregation.

PubMed

Sathish, Veerasamy; Babu, Eththilu; Ramdass, Arumugam; Lu, Zong-Zhan; Velayudham, Murugesan; Thanasekaran, Pounraj; Lu, Kuang-Lieh; Rajagopal, Seenivasan

2014-12-01

Alkoxy bridged binuclear rhenium(I) complexes are used as a probe for the selective and sensitive detection of aggregation of β-amyloid fibrils that are consorted with Alzheimer's disease (AD). The strong binding of the complexes is affirmed by the fluorescence enhancement and calculated binding constant value in the order of 10(5)M(-1) is obtained from the Scatchard plots. The binding of β-amyloid can be attributed to π-π stacking interaction of naphthalene moiety present in rhenium(I) complexes, and it is supported by docking studies. The selectivity is quite high towards other proteins and the formation of fibrils can be observed in the range of 30-40 nm through the AFM and TEM techniques. Copyright © 2014 Elsevier B.V. All rights reserved.

Tree species exhibit complex patterns of distribution in bottomland hardwood forests

Treesearch

Luben D Dimov; Jim L Chambers; Brian R. Lockhart

2013-01-01

& Context Understanding tree interactions requires an insight into their spatial distribution. & Aims We looked for presence and extent of tree intraspecific spatial point pattern (random, aggregated, or overdispersed) and interspecific spatial point pattern (independent, aggregated, or segregated). & Methods We established twelve 0.64-ha plots in natural...

HESI EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of inp...

Engineering cell aggregates through incorporated polymeric microparticles.

PubMed

Ahrens, Caroline C; Dong, Ziye; Li, Wei

2017-10-15

Ex vivo cell aggregates must overcome significant limitations in the transport of nutrients, drugs, and signaling proteins compared to vascularized native tissue. Further, engineered extracellular environments often fail to sufficiently replicate tethered signaling cues and the complex architecture of native tissue. Co-cultures of cells with microparticles (MPs) is a growing field directed towards overcoming many of these challenges by providing local and controlled presentation of both soluble and tethered proteins and small molecules. Further, co-cultured MPs offer a mechanism to better control aggregate architecture and even to report key characteristics of the local microenvironment such as pH or oxygen levels. Herein, we provide a brief introduction to established and developing strategies for MP production including the choice of MP materials, fabrication techniques, and techniques for incorporating additional functionality. In all cases, we emphasize the specific utility of each approach to form MPs useful for applications in cell aggregate co-culture. We review established techniques to integrate cells and MPs. We highlight those strategies that promote targeted heterogeneity or homogeneity, and we describe approaches to engineer cell-particle and particle-particle interactions that enhance aggregate stability and biological response. Finally, we review advances in key application areas of MP aggregates and future areas of development. Cell-scaled polymer microparticles (MPs) integrated into cellular aggregates have been shown to be a powerful tool to direct cell response. MPs have supported the development of healthy cartilage, islets, nerves, and vasculature by the maintenance of soluble gradients as well as by the local presentation of tethered cues and diffusing proteins and small molecules. MPs integrated with pluripotent stem cells have directed in vivo expansion and differentiation. Looking forward, MPs are expected to support both the characterization and development of in vitro tissue systems for applications such as drug testing platforms. However, useful co-cultures must be designed keeping in mind the limitations and attributes of each material strategy within the context of the overall tissue biology. The present review integrates prospectives from materials development, drug delivery, and tissue engineering to provide a toolbox for the development and application of MPs useful for long-term co-culture within cell aggregates. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of different sintering temperature on fly ash based geopolymer artificial aggregate

NASA Astrophysics Data System (ADS)

Abdullah, Alida; Abdullah, Mohd Mustafa Al Bakri; Hussin, Kamarudin; Tahir, Muhammad Faheem Mohd

2017-04-01

This research was conducted to study the mechanical and morphology of fly ash based geopolymer as artificial aggregate at different sintering temperature. The raw material that are used is fly ash, sodium hydroxide, sodium silicate, geopolymer artificial aggregate, Ordinary Portland Cement (OPC), coarse aggregate and fine aggregate. The research starts with the preparation of geopolymer artificial aggregate. Then, geopolymer artificial aggregate will be sintered at six difference temperature that is 400°C, 500°C, 600°C, 700°C, 800°C and 900°C to known at which temperature the geopolymer artificial aggregate will become a lightweight aggregate. In order to characterize the geopolymer artificial aggregate the X-ray Diffraction (XRD) and X-Ray Fluorescence (XRF) was done. The testing and analyses involve for the artificial aggregate is aggregate impact test, specific gravity test and Scanning Electron Microscopy (SEM). After that the process will proceed to produce concrete with two type of different aggregate that is course aggregate and geopolymer artificial aggregate. The testing for concrete is compressive strength test, water absorption test and density test. The result obtained will be compared and analyse.

Assembly of Huntingtin headpiece into α-helical bundles.

PubMed

Ozgur, Beytullah; Sayar, Mehmet

2017-05-24

Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

Effect of crumb rubber on the mechanical properties of crushed recycled pavement materials.

PubMed

Li, Jie; Saberian, Mohammad; Nguyen, Bao Thach

2018-07-15

The low-carbon footprint of using recycled construction and demolition (C&D) aggregates in civil engineering infrastructure applications has been considered to be a significant solution for the replacement of conventional pavement aggregates. Investigations regarding the use of crumb rubber in the base and subbase layers of pavement have been well documented. However, information on the effects of crumb rubber and its size within C&D aggregates as the base/subbase layers is still very limited. In this study, crumb rubber with particle sizes ranging from 400 to 600 μm (fine) to 10-15 mm (coarse), 20 mm recycled crushed concrete (RCC), and 20 mm crushed rock (CR) were used. The crumb rubber was added to the two groups of C&D aggregates at 0.5, 1 and 2% by weight percentages of the aggregates. The effect of crumb rubber on the mechanical properties (such as California bearing ratio, unconfined compressive strength, aggregate crushing value, dynamic lightweight cone penetrometer, Clegg impact value, Los Angeles abrasion values, and resilient modulus) of the C&D aggregates was then examined. Based on the experimental test results, it was found that crumb rubber can be recycled as a waste material for the base and subbase layers in the pavement. Copyright © 2018 Elsevier Ltd. All rights reserved.

Responses to olfactory signals reflect network structure of flower-visitor interactions.

PubMed

Junker, Robert R; Höcherl, Nicole; Blüthgen, Nico

2010-07-01

1. Network analyses provide insights into the diversity and complexity of ecological interactions and have motivated conclusions about community stability and co-evolution. However, biological traits and mechanisms such as chemical signals regulating the interactions between individual species--the microstructure of a network--are poorly understood. 2. We linked the responses of receivers (flower visitors) towards signals (flower scent) to the structure of a highly diverse natural flower-insect network. For each interaction, we define link temperature--a newly developed metric--as the deviation of the observed interaction strength from neutrality, assuming that animals randomly interact with flowers. 3. Link temperature was positively correlated to the specific visitors' responses to floral scents, experimentally examined in a mobile olfactometer. Thus, communication between plants and consumers via phytochemical signals reflects a significant part of the microstructure in a complex network. Negative as well as positive responses towards floral scents contributed to these results, where individual experience was important apart from innate behaviour. 4. Our results indicate that: (1) biological mechanisms have a profound impact on the microstructure of complex networks that underlies the outcome of aggregate statistics, and (2) floral scents act as a filter, promoting the visitation of some flower visitors, but also inhibiting the visitation of others.

A first line of stress defense: small heat shock proteins and their function in protein homeostasis.

PubMed

Haslbeck, Martin; Vierling, Elizabeth

2015-04-10

Small heat shock proteins (sHsps) are virtually ubiquitous molecular chaperones that can prevent the irreversible aggregation of denaturing proteins. sHsps complex with a variety of non-native proteins in an ATP-independent manner and, in the context of the stress response, form a first line of defense against protein aggregation in order to maintain protein homeostasis. In vertebrates, they act to maintain the clarity of the eye lens, and in humans, sHsp mutations are linked to myopathies and neuropathies. Although found in all domains of life, sHsps are quite diverse and have evolved independently in metazoans, plants and fungi. sHsp monomers range in size from approximately 12 to 42kDa and are defined by a conserved β-sandwich α-crystallin domain, flanked by variable N- and C-terminal sequences. Most sHsps form large oligomeric ensembles with a broad distribution of different, sphere- or barrel-like oligomers, with the size and structure of the oligomers dictated by features of the N- and C-termini. The activity of sHsps is regulated by mechanisms that change the equilibrium distribution in tertiary features and/or quaternary structure of the sHsp ensembles. Cooperation and/or co-assembly between different sHsps in the same cellular compartment add an underexplored level of complexity to sHsp structure and function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

PubMed

Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

2015-11-01

Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. Copyright © 2015 Elsevier B.V. All rights reserved.

Artificial Loading of ASC Specks with Cytosolic Antigens

PubMed Central

Sahillioğlu, Ali Can; Özören, Nesrin

2015-01-01

Inflammasome complexes form upon interaction of Nod Like Receptor (NLR) proteins with pathogen associated molecular patterns (PAPMS) inside the cytosol. Stimulation of a subset of inflammasome receptors including NLRP3, NLRC4 and AIM2 triggers formation of the micrometer-sized spherical supramolecular complex called the ASC speck. The ASC speck is thought to be the platform of inflammasome activity, but the reason why a supramolecular complex is preferred against oligomeric platforms remains elusive. We observed that a set of cytosolic proteins, including the model antigen ovalbumin, tend to co-aggregate on the ASC speck. We suggest that co-aggregation of antigenic proteins on the ASC speck during intracellular infection might be instrumental in antigen presentation. PMID:26258904

Luminescent Organometallic Nanomaterials with Aggregation-Induced Emission.

PubMed

Shu, Tong; Wang, Jianxing; Su, Lei; Zhang, Xueji

2018-07-04

Recent researches in metal nanoclusters (NCs) have prompted their promising practical applications in biomedical fields as novel inorganic luminophores. More recently, to further improve the photoluminescence (PL) performance of NCs, the aggregation-induced emission (AIE) effect has been introduced to develop highly luminescent metal NCs and metal complex materials. In this review, we start our discussion from recent progresses on AIE materials developments. Then, we address our understandings on the PL properties of thiolated metal NCs. Subsequently, we link thiolated metal NCs with AIE effect. We also highlight some recent advances in synthesizing the AIE-type metal complex nanomaterials. We finally discuss visions and directions for future development of AIE-type metal complex nanomaterials.

Solvent tuning configurational conversion of lycopene aggregates in organic-aqueous mixing solvent

NASA Astrophysics Data System (ADS)

Dong, Jia; Zhang, Di; Wang, Xin-Yue; Wang, Peng

2018-06-01

In general cases, carotenoid aggregates are prepared in organic-water mixing solvent depending on its hydrophobic character. It is well-known that one of carotenoids, lycopene, is more likely to form typical H-aggregates. In this study, new type lycopene J-aggregates were prepared in DMSO-water mixing solvent with small amount of toluene, which was observed for the first time. We proposed a potential structure model combining with exciton model to interpret the mechanism of spectra changes. Our finding has provided new methods and novel ideas for controlling carotenoid aggregates formation.

Mechanisms of protein stabilization and prevention of protein aggregation by glycerol.

PubMed

Vagenende, Vincent; Yap, Miranda G S; Trout, Bernhardt L

2009-11-24

The stability of proteins in aqueous solution is routinely enhanced by cosolvents such as glycerol. Glycerol is known to shift the native protein ensemble to more compact states. Glycerol also inhibits protein aggregation during the refolding of many proteins. However, mechanistic insight into protein stabilization and prevention of protein aggregation by glycerol is still lacking. In this study, we derive mechanisms of glycerol-induced protein stabilization by combining the thermodynamic framework of preferential interactions with molecular-level insight into solvent-protein interactions gained from molecular simulations. Contrary to the common conception that preferential hydration of proteins in polyol/water mixtures is determined by the molecular size of the polyol and the surface area of the protein, we present evidence that preferential hydration of proteins in glycerol/water mixtures mainly originates from electrostatic interactions that induce orientations of glycerol molecules at the protein surface such that glycerol is further excluded. These interactions shift the native protein toward more compact conformations. Moreover, glycerol preferentially interacts with large patches of contiguous hydrophobicity where glycerol acts as an amphiphilic interface between the hydrophobic surface and the polar solvent. Accordingly, we propose that glycerol prevents protein aggregation by inhibiting protein unfolding and by stabilizing aggregation-prone intermediates through preferential interactions with hydrophobic surface regions that favor amphiphilic interface orientations of glycerol. These mechanisms agree well with experimental data available in the literature, and we discuss the extent to which these mechanisms apply to other cosolvents, including polyols, arginine, and urea.

Structural Design and Economic Evaluation of Roller Compacted Concrete Pavement with Recycled Aggregates

NASA Astrophysics Data System (ADS)

Abut, Yavuz; Taner Yildirim, Salih

2017-10-01

Using recycled aggregates in the concrete offers advantages in many areas such as waste management, energy save and natural resources, conservation of ecological balance, low CO2 emissions, and users are encouraged in this regard to use these materials. In this study, the profit / loss account arising in the structural design phase was investigated when Reclaimed Asphalt Pavement (RAP), which is limited to use in Roller Compacted Concrete (RCC) pavements, was used as coarse aggregate. RAP materials were used as coarse aggregates by the levels of 0%, 15% and 20% and mechanical properties such as compressive strength, flexural strength, splitting tensile strength and modulus of elasticity were investigated. In the last stage, the mechanical properties obtained from these experimental studies were entered into KENSLABS software as input, and the slab layer thicknesses were determined according to three different subgrade conditions and a certain fatigue criterion. According to the results, it has been determined that the use of RAP at a level of 20% is a serious reducing effect on mechanical properties and and the use of RAP at a level of 15% does not bring a great economic benefit but it is reasonable to use it as coarse aggregate in RCC mixes in consideration of environmental effects.

Waste tyre rubberized concrete: properties at fresh and hardened state.

PubMed

Aiello, M A; Leuzzi, F

2010-01-01

The main objective of this paper is to investigate the properties of various concrete mixtures at fresh and hardened state, obtained by a partial substitution of coarse and fine aggregate with different volume percentages of waste tyres rubber particles, having the same dimensions of the replaced aggregate. Workability, unit weight, compressive and flexural strength and post-cracking behaviour were evaluated and a comparison of the results for the different rubcrete mixtures were proposed in order to define the better mix proportions in terms of mechanical properties of the rubberized concrete. Results showed in this paper were also compared to data reported in literature. Moreover, a preliminary geometrical, physical and mechanical characterization on scrap tyre rubber shreds was made. The rubberized concrete mixtures showed lower unit weight compared to plain concrete and good workability. The results of compressive and flexural tests indicated a larger reduction of mechanical properties of rubcrete when replacing coarse aggregate rather than fine aggregate. On the other hand, the post-cracking behaviour of rubberized concrete was positively affected by the substitution of coarse aggregate with rubber shreds, showing a good energy absorption and ductility indexes in the range observed for fibrous concrete, as suggested by standard (ASTM C1018-97, 1997). 2010 Elsevier Ltd. All rights reserved.

Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

PubMed Central

Ismail, Maznah; Tohit, Eusni Rahayu Mohd; Abdullah, Rasedee; Zhang, Yi-Da

2016-01-01

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms. PMID:27800004

Mechanical and Physical Properties of Hydrophobized Lightweight Aggregate Concrete with Sewage Sludge

PubMed Central

Suchorab, Zbigniew; Barnat-Hunek, Danuta; Franus, Małgorzata; Łagód, Grzegorz

2016-01-01

This article is focused on lightweight aggregate-concrete modified by municipal sewage sludge and lightweight aggregate-concrete obtained from light aggregates. The article presents laboratory examinations of material physical parameters. Water absorptivity of the examined material was decreased by the admixture of water emulsion of reactive polysiloxanes. Water transport properties were determined using Time Domain Reflectometry, an indirect technique for moisture detection in porous media. Together with basic physical parameters, the heat conductivity coefficient λ was determined for both types of lightweight aggregate-concrete. Analysis of moisture and heat properties of the examined materials confirmed the usefulness of light aggregates supplemented with sewage sludge for prospective production. PMID:28773442

Aggregated Indexing of Biomedical Time Series Data

PubMed Central

Woodbridge, Jonathan; Mortazavi, Bobak; Sarrafzadeh, Majid; Bui, Alex A.T.

2016-01-01

Remote and wearable medical sensing has the potential to create very large and high dimensional datasets. Medical time series databases must be able to efficiently store, index, and mine these datasets to enable medical professionals to effectively analyze data collected from their patients. Conventional high dimensional indexing methods are a two stage process. First, a superset of the true matches is efficiently extracted from the database. Second, supersets are pruned by comparing each of their objects to the query object and rejecting any objects falling outside a predetermined radius. This pruning stage heavily dominates the computational complexity of most conventional search algorithms. Therefore, indexing algorithms can be significantly improved by reducing the amount of pruning. This paper presents an online algorithm to aggregate biomedical times series data to significantly reduce the search space (index size) without compromising the quality of search results. This algorithm is built on the observation that biomedical time series signals are composed of cyclical and often similar patterns. This algorithm takes in a stream of segments and groups them to highly concentrated collections. Locality Sensitive Hashing (LSH) is used to reduce the overall complexity of the algorithm, allowing it to run online. The output of this aggregation is used to populate an index. The proposed algorithm yields logarithmic growth of the index (with respect to the total number of objects) while keeping sensitivity and specificity simultaneously above 98%. Both memory and runtime complexities of time series search are improved when using aggregated indexes. In addition, data mining tasks, such as clustering, exhibit runtimes that are orders of magnitudes faster when run on aggregated indexes. PMID:27617298

Combined research effort on aggregate road materials

NASA Astrophysics Data System (ADS)

Kuznetsova, Elena; Hoff, Inge; Willy Danielsen, Svein; Wigum, Børge Johannes; Fladvad, Marit; Rieksts, Karlis; Loranger, Benoit; Barbieri, Diego

2017-04-01

In European countries, the average aggregate consumption per capita is 5 tons per year (European Aggregates Association 2016), while the corresponding number in Norway is 11 tons (Neeb 2015). Due to the increased demand for sand and gravel for construction purposes, e.g. in road construction, the last decade has seen a significant trend towards the use of crushed rock aggregates. Neeb (2015) reports that half of the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction, and 33 % of the overall sold tonnage of crushed rock is exported. This resource has been more and more preferred over sand and gravel due to the significant technological development of its process and utilization phase. In Norway, the development and implementation of crushed aggregate technology has been the main approach to solve natural resource scarcity (Danielsen and Kuznetsova 2015). In order to reduce aggregates transportation, it is aimed to use local aggregates and aggregates processed from rock excavations, tunneling, road cuts, etc. One issue focused in this research is the influence from blasting and processing on the final quality of the crushed aggregates, specifically relating to the properties for road construction purposes. It is therefor crucial to plan utilization of available materials for use in different road layers following the same production line. New developments and improved availability of mobile crushing and screening equipment could produce more sustainable and profitable sources of good quality aggregate materials from small volume deposits in proximity to construction sites. One of the biggest challenges today to use these materials is that the pavement design manual sets rigid requirements for pavement layers. Four research projects are being conducted in Norway to improve the use of local materials for road construction. Four aspects are to be covered by the research: a) geological characteristics of the materials, their b) mechanical and c) thermal properties, and d) frost action and susceptibility. The main goal of the PhD topic N1 is to achieve better utilization of aggregate resources through adjusting the production process according to local geological conditions and construction needs. The objective of the PhD project N2 is to look at the design stage and find the way to use these aggregates anyway by changing the road's design (e.g. increasing the thickness of asphalt layer). Fine particles content will also be harder to control due to rock type variability from site to site. Thus, PhD project N3 is going to investigate the effect of the increasing of fines and their mineralogy on frost action related problems during freezing and thawing seasons. Finally, PhD project N4 is investigating how the grading and mineralogy of the crushed rock material affects the heat exchange in road's granular layers and consequently, the frost penetration depth. Combining these PhD studies we aim to create a holistic approach for a new understanding within this very complex area.

The 1992 annual report on scientific programs: A broad research program on the sciences of complexity

NASA Astrophysics Data System (ADS)

In 1992 the Santa Fe Institute hosted more than 100 short- and long-term research visitors who conducted a total of 212 person-months of residential research in complex systems. To date this 1992 work has resulted in more than 50 SFI Working Papers and nearly 150 publications in the scientific literature. The Institute's book series in the sciences of complexity continues to grow, now numbering more than 20 volumes. The fifth annual complex systems summer school brought nearly 60 graduate students and postdoctoral fellows to Santa Fe for an intensive introduction to the field. Research on complex systems - the focus of work at SFI - involves an extraordinary range of topics normally studied in seemingly disparate fields. Natural systems displaying complex adaptive behavior range upwards from DNA through cells and evolutionary systems to human societies. Research models exhibiting complex behavior include spin glasses, cellular automata, and genetic algorithms. Some of the major questions facing complex systems researchers are: (1) explaining how complexity arises from the nonlinear interaction of simple components; (2) describing the mechanisms underlying high-level aggregate behavior of complex systems (such as the overt behavior of an organism, the flow of energy in an ecology, and the Gross National Product (GNP) of an economy); and (3) creating a theoretical framework to enable predictions about the likely behavior of such systems in various conditions.

1992 annual report on scientific programs: A broad research program on the sciences of complexity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-12-31

In 1992 the Santa Fe Institute hosted more than 100 short- and long-term research visitors who conducted a total of 212 person-months of residential research in complex systems. To date this 1992 work has resulted in more than 50 SFI Working Papers and nearly 150 publications in the scientific literature. The Institute`s book series in the sciences of complexity continues to grow, now numbering more than 20 volumes. The fifth annual complex systems summer school brought nearly 60 graduate students and postdoctoral fellows to Santa Fe for an intensive introduction to the field. Research on complex systems-the focus of workmore » at SFI-involves an extraordinary range of topics normally studied in seemingly disparate fields. Natural systems displaying complex adaptive behavior range upwards from DNA through cells and evolutionary systems to human societies. Research models exhibiting complex behavior include spin glasses, cellular automata, and genetic algorithms. Some of the major questions facing complex systems researchers are: (1) explaining how complexity arises from the nonlinear interaction of simple components; (2) describing the mechanisms underlying high-level aggregate behavior of complex systems (such as the overt behavior of an organism, the flow of energy in an ecology, the GNP of an economy); and (3) creating a theoretical framework to enable predictions about the likely behavior of such systems in various conditions.« less

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

DTIC Science & Technology

2009-12-01

found platelet aggregation, thrombus formation and endothelial cell rupture (Fig 1). All these findings demonstrate that PDT damages endothelial...after 0.5 mg/kg verteporfin (i.v.)). (A) 1 h after PDT showing platelet aggregation and thrombus formation; (B) 6 h after PDT showing edema...mechanisms causing thrombi formation. Other mechanisms, such as release of thromboxane from platelets (33) and von Willebrand factor from damaged

High-Resolution Mineralogical Characterization and Biogeochemical Modeling of Uranium Reduction Pathways at the NABIR Field-Research Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

David R. Veblen; Chen Zhu; Lee Krumholz

The effectiveness and feasibility of bioremediation at the field scale cannot be fully assessed until the mechanisms of immobilization and U speciation in the solid matrix are resolved. However, characterization of the immobilized U and its valence states is extremely difficult, because microbially mediated mineral precipitates are generally nanometer (nm)-sized, poorly crystalline, or amorphous. We are developing combined field emission gun--scanning electron microscopy (FEG-SEM, at Indiana University) and FEG transmission electron microscopy (TEM, at Hopkins) to detect and isolate uranium containing phases; (1) method developments for TEM sample preparations and parallel electron energy loss spectroscopy (EELS) determination of uranium valence;more » and (2) to determine the speciation, fate, reactivity, valence states of immobilized uranium, using the state-of-the-art 300-kV, FEG-TEM. We have obtained preliminary results on contaminated sediments from Area 3 at the Oak Ridge Field Research Center (FRC). TEM results show that the sediments contain numerous minerals, including quartz, mica/clay (muscovite and/or illite), rutile, ilmenite, zircon, and an Al-Sr-Ce-Ca phosphate mineral, none of which contain uranium above the EDS detection limit. Substantial U (up to {approx}2 wt.%) is, however, clearly associated with two materials: (1) the Fe oxyhydroxide and (2) clots of a chemically complex material that is likely a mixture of several nm-scale phases. The Fe oxyhydroxide was identified as goethite from its polycrystalline SAED pattern and EDS analysis showing it to be very Fe-rich; the aggregate also displays one of several morphologies that are common for goethite. U is strongly sorbed to goethite in the FRC sediment, and the ubiquitous association with phosphorous suggests that complexes containing both U and P may play an important role in that sorption. Results from bulk analysis and SEM had previously demonstrated the association of U with Fe and thus suggested that U may be sorbed by Fe oxide or oxyhydroxide (Dr. Roh, image presented by David Watson). However, rigorous identification of the host minerals for U requires TEM results such as these involving imaging, electron diffraction, and spectroscopic analysis. An even higher concentration of U occurs in the chemically complex material noted above. These ''clots'' are high in Fe but also contain C, O, Mg, Al, Si, P, S, Cl, K, Ca, Mn, and U. This chemical complexity strongly suggests that they consist of aggregates of carbonate, silicate, phosphate, and sulfate phases, and TEM images also suggest that they may be intergrowths of numerous exceedingly small nanoparticles. EELS and EFTEM studies should be able to resolve these various components and identify precisely where the uranium is in these complex materials. From the results, it is clear that the FEG-SEM and FEG-TEM can readily detect uranium in the FRC samples. The FEG-SEM allows a wide field of view of the samples and can detect U-rich aggregates as small as 20-30 nm. The FEG-TEM can then focus on these aggregates and use SAED, EDS, EFTEM, and PEELS techniques to determine the valence states, structures, and compositional data for these aggregates. This research will provide a crucial component for a complete understanding of the efficacy of uranium bioremediation.« less

Viral Aggregation: Impact on Virus Behavior in the Environment.

PubMed

Gerba, Charles P; Betancourt, Walter Q

2017-07-05

Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

Aggregation and fusion of modified low density lipoprotein.

PubMed

Pentikäinen, M O; Lehtonen, E M; Kovanen, P T

1996-12-01

In atherogenesis, low density lipoprotein (LDL, diameter 22 nm) accumulates in the extracellular space of the arterial intima in the form of aggregates of lipid droplets (droplet diameter up to 400 nm). Here we studied the effects of various established in vitro LDL modifications on LDL aggregation and fusion. LDL was subjected to vortexing, oxidation by copper ions, proteolysis by alpha-chymotrypsin, lipolysis by sphingomyelinase, and nonenzymatic glycosylation, and was induced to form adducts with malondialdehyde or complexes with anti-apoB-100 antibodies. To assess the amount of enlarged LDL-derived structures formed (due to aggregation or fusion), we measured the turbidity of solutions containing modified LDL, and quantified the proportion of modified LDL that 1) sedimented at low-speed centrifugation (14,000 g), 2) floated at an increased rate at high-speed centrifugation (rate zonal flotation at 285,000 gmax), 3) were excluded in size-exclusion column chromatography (exclusion limit 40 MDa), or 4) failed to enter into 0.5%. Fast Lane agarose gel during electrophoresis. To detect whether particle fusion had contributed to the formation of the enlarged LDL-derived structures, particle morphology was examined using negative staining and thin-section transmission electron microscopy. We found that 1) aggregation was induced by the formation of LDL-antibody complexes, malondialdehyde treatment, and glycosylation of LDL; 2) fusion of LDL was induced by proteolysis of LDL by alpha-chymotrypsin; and 3) aggregation and fusion of LDL were induced by vortexing, oxidation by copper ions, and lipolysis by sphingomyclinase of LDL. The various modifications of LDL differed in their ability to induce aggregation and fusion.

Role of streams in myxobacteria aggregate formation

NASA Astrophysics Data System (ADS)

Kiskowski, Maria A.; Jiang, Yi; Alber, Mark S.

2004-10-01

Cell contact, movement and directionality are important factors in biological development (morphogenesis), and myxobacteria are a model system for studying cell-cell interaction and cell organization preceding differentiation. When starved, thousands of myxobacteria cells align, stream and form aggregates which later develop into round, non-motile spores. Canonically, cell aggregation has been attributed to attractive chemotaxis, a long range interaction, but there is growing evidence that myxobacteria organization depends on contact-mediated cell-cell communication. We present a discrete stochastic model based on contact-mediated signaling that suggests an explanation for the initialization of early aggregates, aggregation dynamics and final aggregate distribution. Our model qualitatively reproduces the unique structures of myxobacteria aggregates and detailed stages which occur during myxobacteria aggregation: first, aggregates initialize in random positions and cells join aggregates by random walk; second, cells redistribute by moving within transient streams connecting aggregates. Streams play a critical role in final aggregate size distribution by redistributing cells among fewer, larger aggregates. The mechanism by which streams redistribute cells depends on aggregate sizes and is enhanced by noise. Our model predicts that with increased internal noise, more streams would form and streams would last longer. Simulation results suggest a series of new experiments.

A Proposed Mechanism for the Thermal Denaturation of a Recombinant Bacillus Halmapalus Alpha-amylase - the Effect of Calcium Ions

NASA Technical Reports Server (NTRS)

Nielsen, Anders D.; Pusey, Marc L.; Fuglsang, Claus C.; Westh, Peter

2003-01-01

The thermal stability of a recombinant alpha-amylase from Bacillus halmapalus alpha-amylase (BHA) has been investigated using circular dichroism spectroscopy (CD) and differential scanning calorimetry (DSC). This alpha-amylase is homologous to other Bacillus alpha-amylases where previous crystallographic studies have identified the existence of 3 calcium binding sites in the structure. Denaturation of BHA is irreversible with a Tm of approximately 89 C, and DSC thermograms can be described using a one-step irreversible model. A 5 C increase in T(sub m) in the presence of 10 fold excess CaCl2 was observed. However, a concomitant increase in the tendency to aggregate was also observed. The presence of 30-40 fold excess calcium chelator (EDTA or EGTA) results in a large destabilization of BHA corresponding to about 40 C lower T(sub m), as determined by both CD and DSC. Ten fold excess EGTA reveals complex DSC thermograms corresponding to both reversible and irreversible transitions, which possibly originate from different populations of BHA:calcium complexes. The observations in the present study have, in combination with structural information of homologous alpha-amylases, provided the basis for the proposal of a simple denaturation mechanism of BHA. The proposed mechanism describes the irreversible thermal denaturation of different BHA:calcium complexes and the calcium binding equilibrium involved. Furthermore, the model accounts for a temperature induced reversible structural change associated with calcium binding.

Zebrafish models of BAG3 myofibrillar myopathy suggest a toxic gain of function leading to BAG3 insufficiency.

PubMed

Ruparelia, Avnika A; Oorschot, Viola; Vaz, Raquel; Ramm, Georg; Bryson-Richardson, Robert J

2014-12-01

Mutations in the co-chaperone Bcl2-associated athanogene 3 (BAG3) can cause myofibrillar myopathy (MFM), a childhood-onset progressive muscle disease, characterized by the formation of protein aggregates and myofibrillar disintegration. In contrast to other MFM-causing proteins, BAG3 has no direct structural role, but regulates autophagy and the degradation of misfolded proteins. To investigate the mechanism of disease in BAG3-related MFM, we expressed wild-type BAG3 or the dominant MFM-causing BAG3 (BAG3(P209L)) in zebrafish. Expression of the mutant protein results in the formation of aggregates that contain wild-type BAG3. Through the stimulation and inhibition of autophagy, we tested the prevailing hypothesis that impaired autophagic function is responsible for the formation of protein aggregates. Contrary to the existing theory, our studies reveal that inhibition of autophagy is not sufficient to induce protein aggregation. Expression of the mutant protein, however, did not induce myofibrillar disintegration and we therefore examined the effect of knocking down Bag3 function. Loss of Bag3 resulted in myofibrillar disintegration, but not in the formation of protein aggregates. Remarkably, BAG3(P209L) is able to rescue the myofibrillar disintegration phenotype, further demonstrating that its function is not impaired. Together, our knockdown and overexpression experiments identify a mechanism whereby BAG3(P209L) aggregates form, gradually reducing the pool of available BAG3, which eventually results in BAG3 insufficiency and myofibrillar disintegration. This mechanism is consistent with the childhood onset and progressive nature of MFM and suggests that reducing aggregation through enhanced degradation or inhibition of nucleation would be an effective therapy for this disease.

Early-Stage Aggregation of Human Islet Amyloid Polypeptide

NASA Astrophysics Data System (ADS)

Guo, Ashley; de Pablo, Juan

Human islet amyloid polypeptide (hIAPP, or human amylin) is implicated in the development of type II diabetes. hIAPP is known to aggregate into amyloid fibrils; however, it is prefibrillar oligomeric species, rather than mature fibrils, that are proposed to be cytotoxic. In order to better understand the role of hIAPP aggregation in the onset of disease, as well as to design effective diagnostics and therapeutics, it is crucial to understand the mechanism of early-stage hIAPP aggregation. In this work, we use atomistic molecular dynamics simulations combined with multiple advanced sampling techniques to examine the formation of the hIAPP dimer and trimer. Metadynamics calculations reveal a free energy landscape for the hIAPP dimer, which suggest multiple possible transition pathways. We employ finite temperature string method calculations to identify favorable pathways for dimer and trimer formation, along with relevant free energy barriers and intermediate structures. Results provide valuable insights into the mechanisms and energetics of hIAPP aggregation. In addition, this work demonstrates that the finite temperature string method is an effective tool in the study of protein aggregation. Funded by National Institute of Standards and Technology.

The breakup mechanism of biomolecular and colloidal aggregates in a shear flow

NASA Astrophysics Data System (ADS)

Ó Conchúir, Breanndán; Zaccone, Alessio

2014-03-01

The theory of self-assembly of colloidal particles in shear flow is incomplete. Previous analytical approaches have failed to capture the microscopic interplay between diffusion, shear and intermolecular interactions which controls the aggregates fate in shear. In this work we analytically solved the drift-diffusion equation for the breakup rate of a dimer in flow. Then applying rigidity percolation theory, we found that the lifetime of a generic cluster formed under shear is controlled by the typical lifetime of a single bond in its interior, which in turn depends on the efficiency of the stress transmitted from other bonds in the cluster. We showed that aggregate breakup is a thermally-activated process where the activation energy is controlled by the interplay between intermolecular forces and the shear drift, and where structural parameters determine whether cluster fragmentation or surface erosion prevails. In our latest work, we analyzed floppy modes and nonaffine deformations to derive a lower bound on the fractal dimension df below which aggregates are mechanically unstable, ie. for large aggregates df ~= 2.4. This theoretical framework is in quantitative agreement with experiments and can be used for population balance modeling of colloidal and protein aggregation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes may contain aggregation-prone regions.

PubMed

Kumar, Sandeep; Singh, Satish K; Wang, Xiaoling; Rup, Bonita; Gill, Davinder

2011-05-01

Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.

Utilizing dynamic light scattering as a process analytical technology for protein folding and aggregation monitoring in vaccine manufacturing.

PubMed

Yu, Zhou; Reid, Jennifer C; Yang, Yan-Ping

2013-12-01

Protein aggregation is a common challenge in the manufacturing of biological products. It is possible to minimize the extent of aggregation through timely measurement and in-depth characterization of aggregation. In this study, we demonstrated the use of dynamic light scattering (DLS) to monitor inclusion body (IB) solubilization, protein refolding, and aggregation near the production line of a recombinant protein-based vaccine candidate. Our results were in good agreement with those measured by size-exclusion chromatography. DLS was also used to characterize the mechanism of aggregation. As DLS is a quick, nonperturbing technology, it can potentially be used as an at-line process analytical technology to ensure complete IB solubilization and aggregate-free refolding. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Statistical physics approaches to Alzheimer's disease

NASA Astrophysics Data System (ADS)

Peng, Shouyong

Alzheimer's disease (AD) is the most common cause of late life dementia. In the brain of an AD patient, neurons are lost and spatial neuronal organizations (microcolumns) are disrupted. An adequate quantitative analysis of microcolumns requires that we automate the neuron recognition stage in the analysis of microscopic images of human brain tissue. We propose a recognition method based on statistical physics. Specifically, Monte Carlo simulations of an inhomogeneous Potts model are applied for image segmentation. Unlike most traditional methods, this method improves the recognition of overlapped neurons, and thus improves the overall recognition percentage. Although the exact causes of AD are unknown, as experimental advances have revealed the molecular origin of AD, they have continued to support the amyloid cascade hypothesis, which states that early stages of aggregation of amyloid beta (Abeta) peptides lead to neurodegeneration and death. X-ray diffraction studies reveal the common cross-beta structural features of the final stable aggregates-amyloid fibrils. Solid-state NMR studies also reveal structural features for some well-ordered fibrils. But currently there is no feasible experimental technique that can reveal the exact structure or the precise dynamics of assembly and thus help us understand the aggregation mechanism. Computer simulation offers a way to understand the aggregation mechanism on the molecular level. Because traditional all-atom continuous molecular dynamics simulations are not fast enough to investigate the whole aggregation process, we apply coarse-grained models and discrete molecular dynamics methods to increase the simulation speed. First we use a coarse-grained two-bead (two beads per amino acid) model. Simulations show that peptides can aggregate into multilayer beta-sheet structures, which agree with X-ray diffraction experiments. To better represent the secondary structure transition happening during aggregation, we refine the model to four beads per amino acid. Typical essential interactions, such as backbone hydrogen bond, hydrophobic and electrostatic interactions, are incorporated into our model. We study the aggregation of Abeta16-22, a peptide that can aggregate into a well-ordered fibrillar structure in experiments. Our results show that randomly-oriented monomers can aggregate into fibrillar subunits, which agree not only with X-ray diffraction experiments but also with solid-state NMR studies. Our findings demonstrate that coarse-grained models and discrete molecular dynamics simulations can help researchers understand the aggregation mechanism of amyloid peptides.

Molecular dynamics studies of protein folding and aggregation

NASA Astrophysics Data System (ADS)

Ding, Feng

This thesis applies molecular dynamics simulations and statistical mechanics to study: (i) protein folding; and (ii) protein aggregation. Most small proteins fold into their native states via a first-order-like phase transition with a major free energy barrier between the folded and unfolded states. A set of protein conformations corresponding to the free energy barrier, Delta G >> kBT, are the folding transition state ensemble (TSE). Due to their evasive nature, TSE conformations are hard to capture (probability ∝ exp(-DeltaG/k BT)) and characterize. A coarse-grained discrete molecular dynamics model with realistic steric constraints is constructed to reproduce the experimentally observed two-state folding thermodynamics. A kinetic approach is proposed to identify the folding TSE. A specific set of contacts, common to the TSE conformations, is identified as the folding nuclei which are necessary to be formed in order for the protein to fold. Interestingly, the amino acids at the site of the identified folding nuclei are highly conserved for homologous proteins sharing the same structures. Such conservation suggests that amino acids that are important for folding kinetics are under selective pressure to be preserved during the course of molecular evolution. In addition, studies of the conformations close to the transition states uncover the importance of topology in the construction of order parameter for protein folding transition. Misfolded proteins often form insoluble aggregates, amyloid fibrils, that deposit in the extracellular space and lead to a type of disease known as amyloidosis. Due to its insoluble and non-crystalline nature, the aggregation structure and, thus the aggregation mechanism, has yet to be uncovered. Discrete molecular dynamics studies reveal an aggregate structure with the same structural signatures as in experimental observations and show a nucleation aggregation scenario. The simulations also suggest a generic aggregation mechanism that globular proteins under a denaturing environment partially unfold and aggregate by forming stabilizing hydrogen bonds between the backbones of the partial folded substructures. Proteins or peptides rich in alpha-helices also aggregate into beta-rich amyloid fibrils. Upon aggregation, the protein or peptide undergoes a conformational transition from alpha-helices to beta-sheets. The transition of alpha-helix to beta-hairpin (two-stranded beta-sheet) is studied in an all-heavy-atom discrete molecular dynamics model of a polyalanine chain. An entropical driving scenario for the alpha-helix to beta-hairpin transition is discovered.

Compensatory dynamics stabilize aggregate community properties in response to multiple types of perturbations.

PubMed

Brown, Bryan L; Downing, Amy L; Leibold, Mathew A

2016-08-01

Compensatory dynamics are an important suite of mechanisms that can stabilize community and ecosystem attributes in systems subject to environmental fluctuations. However, few experimental investigations of compensatory dynamics have addressed these mechanisms in systems of real-world complexity, and existing evidence relies heavily on correlative analyses, retrospective examination, and experiments in simple systems. We investigated the potential for compensatory dynamics to stabilize plankton communities in plankton mesocosm systems of real-world complexity. We employed four types of perturbations including two types of nutrient pulses, shading, and acidification. To quantify how communities responded to these perturbations, we used a measure of community-wide synchrony combined with spectral analysis that allowed us to assess timescale-specific community dynamics, for example, whether dynamics were synchronous at some timescales but compensatory at others. The 150-d experiment produced 32-point time series of all zooplankton taxa in the mesocosms. We then used those time series to evaluate total zooplankton biomass as an aggregate property and to evaluate community dynamics. For three of our four perturbation types, total zooplankton biomass was significantly less variable in systems with environmental variation than in constant environments. For the same three perturbation types, community-wide synchrony was much lower in fluctuating environments than in the constant environment, particularly at longer timescales (periods ≈ 60 d). Additionally, there were strong negative correlations between population temporal variances and the level of community-wide synchrony. Taken together, these results strongly imply that compensatory interactions between species stabilized total biomass in response to perturbations. Diversity did not differ significantly across either treatments or perturbation types, thus ruling out several classes of mechanisms driven by changes in diversity. We also used several pieces of secondary evidence to evaluate the particular mechanism behind compensatory responses since a wide variety of mechanisms are hypothesized to produce compensatory dynamics. We concluded that fluctuation dependent endogenous cycles that occur as a consequence of consumer-resource interactions in competitive communities were the most likely explanation for the compensatory dynamics observed in our experiment. As with our previous work, scale-dependent dynamics were also a key to understanding compensatory dynamics in these experimental communities. © 2016 by the Ecological Society of America.

Interaction of two cylinders in shear flow at low Wi

NASA Astrophysics Data System (ADS)

Brown, M. J.; Leal, L. G.

2001-11-01

Experiments [Lyon et al., 2001; Boussima et al., 1996; Michelle et al., 1977] have shown that non-Brownian, non-Colloidal, and charge-neutral particles, when suspended in viscoelastic media and subjected to shear, will aggregate and flow-align above a critical shear rate Wi O(10). Giesekus [1978] proposed a mechanism for aggregation based on the attractive hoop thrusts about two particles in viscoelastic flow. This pairwise mechanism of attraction is borne out in studies of sedimenting particles [Feng & Joseph, 1996; Joseph et al., 1994], and seems a valid explanation for the aggregation observed in sedimenting suspensions over all Wi > Re [Joseph et al., 1994; Phillips, 1996.] Consideration of the flow around two particles in shear would lead one to expect attraction by this hoop thrust mechanism as well. However, it remains unclear why shear-induced aggregation only occurs above a critical Wi. A first step in understanding this criticality is to establish the low Wi behavior of two particles in shear. In this talk, we report on the interaction of two freely-mobile cylinders as predicted by an n-th order fluid computation.

Microscopic mechanism of nanocrystal formation from solution by cluster aggregation and coalescence

PubMed Central

Hassan, Sergio A.

2011-01-01

Solute-cluster aggregation and particle fusion have recently been suggested as alternative routes to the classical mechanism of nucleation from solution. The role of both processes in the crystallization of an aqueous electrolyte under controlled salt addition is here elucidated by molecular dynamics simulation. The time scale of the simulation allows direct observation of the entire crystallization pathway, from early events in the prenucleation stage to the formation of a nanocrystal in equilibrium with concentrated solution. The precursor originates in a small amorphous aggregate stabilized by hydration forces. The core of the nucleus becomes crystalline over time and grows by coalescence of the amorphous phase deposited at the surface. Imperfections of ion packing during coalescence promote growth of two conjoint crystallites. A parameter of order and calculated cohesive energies reflect the increasing crystalline order and stress relief at the grain boundary. Cluster aggregation plays a major role both in the formation of the nucleus and in the early stages of postnucleation growth. The mechanism identified shares common features with nucleation of solids from the melt and of liquid droplets from the vapor. PMID:21428633

Infectious burden and atherosclerosis: A clinical issue

PubMed Central

Sessa, Rosa; Pietro, Marisa Di; Filardo, Simone; Turriziani, Ombretta

2014-01-01

Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

PubMed Central

Grainick, H R; Williams, S B; McKeown, L P; Rick, M E; Maisonneuve, P; Jenneau, C; Sultan, Y

1985-01-01

We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia. Images PMID:2932469

Fluorescence spectroscopy as a specific tool for the interaction study of two surfactants with natural and synthetic organic compounds

NASA Astrophysics Data System (ADS)

Jung, Aude-Valérie; Frochot, Céline; Bersillon, Jean-Luc

2016-04-01

Four different techniques were used to study the binding of cationic cetyltrimethylammonium bromide (CTAB) and non-ionic nonylphenylethoxyl (NPE) surfactants to three synthetic organic components that mimic humic-like aggregates and to two natural aggregated humic substances (HS) extracted from aquatic suspended matter. The composition of synthetic organic components were chosen to be similar to high molecular weight highly processed terrigenous HS and low and high molecular weight less processed terrigenous (or aquatic terrigenous) HS. The natural HS were extracted under two different meteorological conditions (rainy and dry periods). No significant interaction between the non-ionic surfactant and any of the studied compounds was found. Concerning CTAB; pH, conductivity and turbidity measurements, along with fluorescence spectroscopy were combined to provide a better understanding of interactions between organic aggregates and the surfactant. The spectroscopic data show that a "highly processed terrigenous HS" fluorophore interacts in a different way with the cationic surfactant than an "aquatic terrigenous (or less processed terrigenous) HS" fluorophore does. Under similar conditions, some spectral changes in the fluorescence signal are correlated to changes in non-specific physical-chemical parameters (pH, turbidity, conductivity) for the organic compounds tested. The complexation mechanism is essentially governed by charge neutralization, which can be monitored specifically by the fluorescence of the organic moieties.

Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

PubMed

Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

2016-02-01

3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural stability of E. coli transketolase to temperature and pH denaturation.

PubMed

Jahromi, Raha R F; Morris, Phattaraporn; Martinez-Torres, Ruben J; Dalby, Paul A

2011-09-10

We have previously shown that the denaturation of TK with urea follows a non-aggregating though irreversible denaturation pathway in which the cofactor binding appears to become altered but without dissociating, then followed at higher urea by partial denaturation of the homodimer prior to any further unfolding or dissociation of the two monomers. Urea is not typically present during biocatalysis, whereas access to TK enzymes that retain activity at increased temperature and extreme pH would be useful for operation under conditions that increase substrate and product stability or solubility. To provide further insight into the underlying causes of its deactivation in process conditions, we have characterised the effects of temperature and pH on the structure, stability, aggregation and activity of Escherichia coli transketolase. The activity of TK was initially found to progressively improve after pre-incubation at increasing temperatures. Loss of activity at higher temperature and low pH resulted primarily from protein denaturation and subsequent irreversible aggregation. By contrast, high pH resulted in the formation of a native-like state that was only partially inactive. The apo-TK enzyme structure content also increased at pH 9 to converge on that of the holo-TK. While cofactor dissociation was previously proposed for high pH deactivation, the observed structural changes in apo-TK but not holo-TK indicate a more complex mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

Functionalized Carbon Nanotubes in Modified Plant Oil Composites.

NASA Astrophysics Data System (ADS)

McAninch, Ian M.; Wool, Richard P.

2007-03-01

Carbon nanotubes (CNTs) with their impressive mechanical properties are ideal reinforcement material. Acrylated epoxidized soy oil (AESO) has been previously shown to have favorable interactions with carbon nanotubes; however a mixture of aggregates and dispersed tubes were found even at low CNT concentrations. In order to prevent re-aggregation, the CNTs were functionalized with a 10 carbon long aliphatic chain. These aliphatic chains are similar to the fatty acids that make up soy oil. Functionalization was verified using XPS and IR spectroscopy. These functionalized CNTs were dispersed by mechanical shear mixing into AESO both with and without styrene as a comonomer. No large aggregates were observed in the liquid, uncured, samples or in the final cured composites. Dispersion in the solid composites was verified using optical and electron microscopy. Better dispersion also resulted in improved mechanical properties.

Charging of Aggregate Grains in Astrophysical Environments

NASA Astrophysics Data System (ADS)

Ma, Qianyu; Matthews, Lorin S.; Land, Victor; Hyde, Truell W.

2013-02-01

The charging of dust grains in astrophysical environments has been investigated with the assumption that these grains are homogeneous spheres. However, there is evidence which suggests that many grains in astrophysical environments are irregularly shaped aggregates. Recent studies have shown that aggregates acquire higher charge-to-mass ratios due to their complex structures, which in turn may alter their subsequent dynamics and evolution. In this paper, the charging of aggregates is examined including secondary electron emission and photoemission in addition to primary plasma currents. The results show that the equilibrium charge on aggregates can differ markedly from spherical grains with the same mass, but that the charge can be estimated for a given environment based on structural characteristics of the grain. The "small particle effect" due to secondary electron emission is also important for de terming the charge of micron-sized aggregates consisting of nano-sized particles.

Real-time monitoring of quorum sensing in 3D-printed bacterial aggregates using scanning electrochemical microscopy.

PubMed

Connell, Jodi L; Kim, Jiyeon; Shear, Jason B; Bard, Allen J; Whiteley, Marvin

2014-12-23

Microbes frequently live in nature as small, densely packed aggregates containing ∼10(1)-10(5) cells. These aggregates not only display distinct phenotypes, including resistance to antibiotics, but also, serve as building blocks for larger biofilm communities. Aggregates within these larger communities display nonrandom spatial organization, and recent evidence indicates that this spatial organization is critical for fitness. Studying single aggregates as well as spatially organized aggregates remains challenging because of the technical difficulties associated with manipulating small populations. Micro-3D printing is a lithographic technique capable of creating aggregates in situ by printing protein-based walls around individual cells or small populations. This 3D-printing strategy can organize bacteria in complex arrangements to investigate how spatial and environmental parameters influence social behaviors. Here, we combined micro-3D printing and scanning electrochemical microscopy (SECM) to probe quorum sensing (QS)-mediated communication in the bacterium Pseudomonas aeruginosa. Our results reveal that QS-dependent behaviors are observed within aggregates as small as 500 cells; however, aggregates larger than 2,000 bacteria are required to stimulate QS in neighboring aggregates positioned 8 μm away. These studies provide a powerful system to analyze the impact of spatial organization and aggregate size on microbial behaviors.

Involvement of cell surface TG2 in the aggregation of K562 cells triggered by gluten.

PubMed

Feriotto, G; Calza, R; Bergamini, C M; Griffin, M; Wang, Z; Beninati, S; Ferretti, V; Marzola, E; Guerrini, R; Pagnoni, A; Cavazzini, A; Casciano, F; Mischiati, C

2017-03-01

Gluten-induced aggregation of K562 cells represents an in vitro model reproducing the early steps occurring in the small bowel of celiac patients exposed to gliadin. Despite the clear involvement of TG2 in the activation of the antigen-presenting cells, it is not yet clear in which compartment it occurs. Herein we study the calcium-dependent aggregation of these cells, using either cell-permeable or cell-impermeable TG2 inhibitors. Gluten induces efficient aggregation when calcium is absent in the extracellular environment, while TG2 inhibitors do not restore the full aggregating potential of gluten in the presence of calcium. These findings suggest that TG2 activity is not essential in the cellular aggregation mechanism. We demonstrate that gluten contacts the cells and provokes their aggregation through a mechanism involving the A-gliadin peptide 31-43. This peptide also activates the cell surface associated extracellular TG2 in the absence of calcium. Using a bioinformatics approach, we identify the possible docking sites of this peptide on the open and closed TG2 structures. Peptide docks with the closed TG2 structure near to the GTP/GDP site, by establishing molecular interactions with the same amino acids involved in stabilization of GTP binding. We suggest that it may occur through the displacement of GTP, switching the TG2 structure from the closed to the active open conformation. Furthermore, docking analysis shows peptide binding with the β-sandwich domain of the closed TG2 structure, suggesting that this region could be responsible for the different aggregating effects of gluten shown in the presence or absence of calcium. We deduce from these data a possible mechanism of action by which gluten makes contact with the cell surface, which could have possible implications in the celiac disease onset.

Stable J-aggregation enabled dual photoacoustic and fluorescence nanoparticles for intraoperative cancer imaging

NASA Astrophysics Data System (ADS)

Shakiba, Mojdeh; Ng, Kenneth K.; Huynh, Elizabeth; Chan, Harley; Charron, Danielle M.; Chen, Juan; Muhanna, Nidal; Foster, F. Stuart; Wilson, Brian C.; Zheng, Gang

2016-06-01

J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications.J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/C5NR08165C

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

PubMed Central

Specht, Sebastian; Miller, Stephanie B.M.

2011-01-01

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID:22065637

HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE'S EXPOSURE FACTORS DATABASE FOR AGGREGATE AND CUMULATIVE RISK ASSESSMENT

EPA Science Inventory

In recent years, the risk analysis community has broadened its use of complex aggregate and cumulative residential exposure models (e.g., to meet the requirements of the 1996 Food Quality Protection Act). The value of these models is their ability to incorporate a range of input...

Regularized learning of linear ordered-statistic constant false alarm rate filters (Conference Presentation)

NASA Astrophysics Data System (ADS)

Havens, Timothy C.; Cummings, Ian; Botts, Jonathan; Summers, Jason E.

2017-05-01

The linear ordered statistic (LOS) is a parameterized ordered statistic (OS) that is a weighted average of a rank-ordered sample. LOS operators are useful generalizations of aggregation as they can represent any linear aggregation, from minimum to maximum, including conventional aggregations, such as mean and median. In the fuzzy logic field, these aggregations are called ordered weighted averages (OWAs). Here, we present a method for learning LOS operators from training data, viz., data for which you know the output of the desired LOS. We then extend the learning process with regularization, such that a lower complexity or sparse LOS can be learned. Hence, we discuss what 'lower complexity' means in this context and how to represent that in the optimization procedure. Finally, we apply our learning methods to the well-known constant-false-alarm-rate (CFAR) detection problem, specifically for the case of background levels modeled by long-tailed distributions, such as the K-distribution. These backgrounds arise in several pertinent imaging problems, including the modeling of clutter in synthetic aperture radar and sonar (SAR and SAS) and in wireless communications.

The Tim9p–Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier

PubMed Central

Curran, Sean P.; Leuenberger, Danielle; Oppliger, Wolfgang; Koehler, Carla M.

2002-01-01

The soluble Tim9p–Tim10p (Tim, translocase of inner membrane) complex of the mitochondrial intermembrane space mediates the import of the carrier proteins and is a component of the TIM22 import system. The mechanism by which the Tim9p–Tim10p complex assembles and binds the carriers is not well understood, but previous studies have proposed that the conserved cysteine residues in the ‘twin CX3C’ motif coordinate zinc and potentially generate a zinc-finger-like structure that binds to the matrix loops of the carrier proteins. Here we have purified the native and recombinant Tim9p–Tim10p complex, and show that both complexes resemble each other and consist of three Tim9p and three Tim10p. Results from inductively coupled plasma–mass spectrometry studies failed to detect zinc in the Tim9p–Tim10p complex. Instead, the cysteine residues seemingly formed disulfide linkages. The Tim9p–Tim10p complex bound specifically to the transmembrane domains of the ADP/ATP carrier, but had no affinity for Tim23p, an inner membrane protein that is inserted via the TIM22 complex. The chaperone-like Tim9p–Tim10p complex thus may prevent aggregation of the unfolded carrier proteins in the aqueous intermembrane space. PMID:11867522

Microwave-induced formation of oligomeric amyloid aggregates.

PubMed

Lee, Wonseok; Choi, Yeseong; Lee, Sang Won; Kim, Insu; Lee, Dongtak; Hong, Yoochan; Lee, Gyudo; Yoon, Dae Sung

2018-08-24

Amyloid aggregates have emerged as a significant hallmark of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Although it has been recently reported that microwave heating induces amyloid aggregation compared with conventional heating methods, the mechanism of amyloid aggregate induction has remained unclear. In this study, we investigated the formation of oligomeric amyloid aggregates (OAAs) by microwave irradiation at microscale volumes of solution. Microwave irradiation of protein monomer solution triggered rapid formation of OAAs within 7 min. We characterized the formation of OAAs using atomic force microscopy, thioflavin T fluorescent assay and circular dichroism. In the microwave system, we also investigated the inhibitory effect on the formation of amyloid aggregates by L-ascorbic acid as well as enhanced amyloid aggregation by silver nanomaterials such as nanoparticles and nanowires. We believe that microwave technology has the potential to facilitate the study of amyloid aggregation in the presence of chemical agents or nanomaterials.

Feasibility Study on Manufacturing Lightweight Aggregates from Water Purification Sludge

NASA Astrophysics Data System (ADS)

Peng, Ching-Fang; Chen, How-Ji

2018-02-01

This study mainly discussed the feasibility of manufacturing lightweight aggregates from water purification sludge in Taiwan. They were analysed for the physical and chemical composition before the sintering test for lightweight aggregates in a laboratory. Then the physical and mechanical properties of the synthesized aggregates were assessed. The result showed that the chemical composition of sludge in the water purification plants was within the appropriate range for manufacturing lightweight aggregate as proposed in the literature. The sintering test demonstrated that the particle density of aggregates from the ten types of water purification sludge were mostly less than 1.8 g/cm3. In addition, the dry unit weight, the organic impurity, the ignition loss, and other characteristics of synthesized aggregates met the requirement of CNS standards, while its water absorption and crushing strength also fulfilled the general commercial specifications. Therefore, reclamation of water purification sludge for production of lightweight aggregate is indeed feasible.

TOPICAL REVIEW: The physics of chromatin

NASA Astrophysics Data System (ADS)

Schiessel, Helmut

2003-05-01

Recent progress has been made in the understanding of the physical properties of chromatin - the dense complex of DNA and histone proteins that occupies the nuclei of plant and animal cells. Here I will focus on the two lowest levels of the hierarchy of DNA folding into the chromatin complex. (i) The nucleosome, the chromatin repeating unit consisting of a globular aggregate of eight histone proteins with the DNA wrapped around it: its overcharging, the DNA unwrapping transition, the 'sliding' of the octamer along the DNA. (ii) The 30 nm chromatin fibre, the necklace-like structure of nucleosomes connected via linker DNA: its geometry, its mechanical properties under stretching and its response to changing ionic conditions. I will stress that chromatin combines two seemingly contradictory features: (1) high compaction of DNA within the nuclear envelope and, at the same time, (2) accessibility to genes, promoter regions and gene regulatory sequences.

Structural basis for the antifolding activity of a molecular chaperone

NASA Astrophysics Data System (ADS)

Huang, Chengdong; Rossi, Paolo; Saio, Tomohide; Kalodimos, Charalampos G.

2016-09-01

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.

Constitutive Models Based on Compressible Plastic Flows

NASA Technical Reports Server (NTRS)

Rajendran, A. M.

1983-01-01

The need for describing materials under time or cycle dependent loading conditions has been emphasized in recent years by several investigators. In response to the need, various constitutive models describing the nonlinear behavior of materials under creep, fatigue, or other complex loading conditions were developed. The developed models for describing the fully dense (non-porous) materials were mostly based on uncoupled plasticity theory. The improved characterization of materials provides a better understanding of the structual response under complex loading conditions. The pesent studies demonstrate that the rate or time dependency of the response of a porous aggregate can be incorporated into the nonlinear constitutive behavior of a porous solid by appropriately modeling the incompressible matrix behavior. It is also sown that the yield function which wads determined by a continuum mechanics approach must be verified by appropriate experiments on void containing sintered materials in order to obtain meaningful numbers for the constants that appear in the yield function.

Application of Data Provenance in Healthcare Analytics Software: Information Visualisation of User Activities

PubMed Central

Xu, Shen; Rogers, Toby; Fairweather, Elliot; Glenn, Anthony; Curran, James; Curcin, Vasa

2018-01-01

Data provenance is a technique that describes the history of digital objects. In health data settings, it can be used to deliver auditability and transparency, and to achieve trust in a software system. However, implementing data provenance in analytics software at an enterprise level presents a different set of challenges from the research environments where data provenance was originally devised. In this paper, the challenges of reporting provenance information to the user is presented. Provenance captured from analytics software can be large and complex and visualizing a series of tasks over a long period can be overwhelming even for a domain expert, requiring visual aggregation mechanisms that fit with complex human cognitive activities involved in the process. This research studied how provenance-based reporting can be integrated into a health data analytics software, using the example of Atmolytics visual reporting tool. PMID:29888084

Protein aggregates as depots for the release of biologically active compounds.

PubMed

Artemova, Natalya V; Kasakov, Alexei S; Bumagina, Zoya M; Lyutova, Elena M; Gurvits, Bella Ya

2008-12-12

Protein misfolding and aggregation is one of the most serious problems in cell biology, molecular medicine, and biotechnology. Misfolded proteins interact with each other or with other proteins in non-productive or damaging ways. However, a new paradigm arises that protein aggregation may be exploited by nature to perform specific functions in different biological contexts. From this consideration, acceleration of stress-induced protein aggregation triggered by any factor resulting in the formation of soluble aggregates may have paradoxical positive consequences. Here, we suggest that amorphous aggregates can act as a source for the release of biologically active proteins after removal of stress conditions. To address this concept, we investigated the kinetics of thermal aggregation in vitro of yeast alcohol dehydrogenase (ADH) as a model substrate in the presence of two amphiphilic peptides: Arg-Phe or Ala-Phe-Lys. Using dynamic light scattering (DLS) and turbidimetry, we have demonstrated that under mild stress conditions the concentration-dependent acceleration of ADH aggregation by these peptides results in formation of large but soluble complexes of proteins prone to refolding.

An overview of aggregate resources in the United States

USGS Publications Warehouse

Langer, William H.; Scott, P.W.; Bristow, C.M.

2002-01-01

In 2000 the USA produced about 2.7 billion tonnes of aggregate worth about $13.7 billion. Both crushed stone and sand and gravel are produced in virtually every State, although limited quantities are available in the Gulf Coastal Plain, the Colorado Plateau , the Wyoming Basin and the Great Plains. Prices vary depending on the product and location. Most aggregates are transported by road, and minor amounts by railroad, barge on navigable inland channels, and through the Great Lake ports. Imports and exports of aggregates are very minor. A major amount f crushed stone aggregates is consumed by concrete aggregate. Recycled aggregates account for about 8% of total demand, although the amount recycled is thought to be increasing. Current issues facing the inductry unclude the differences in quality specifications between States, adjusting to the increasing concern for the impact of aggregate mining on the environmentm, health issues from particulate matter and crystalline silica, and the complexity of obtaining permits for extraction. Redcustion in the number od companies extracting aggregrates is likely to occur through acquisitions.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering.

PubMed

Ho, Tuan Anh; Greathouse, Jeffery A; Wang, Yifeng; Criscenti, Louise J

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of the aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering

DOE PAGES

Ho, Tuan Anh; Greathouse, Jeffery A.; Wang, Yifeng; ...

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of themore » aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.« less

A simple system for the identification of fluorescent dyes capable of reporting differences in secondary structure and hydrophobicity among amyloidogenic protein oligomers

NASA Astrophysics Data System (ADS)

Yates, Emma

2012-02-01

Thioflavin T and Congo Red are fluorescent dyes that are commonly used to identify the presence of amyloid structures, ordered protein aggregates. Despite the ubiquity of their use, little is known about their mechanism of interaction with amyloid fibrils, or whether other dyes, whose photophysics indicate that they may be more responsive to differences in macromolecular secondary structure and hydrophobicity, would be better suited to the identification of pathologically relevant oligomeric species in amyloid diseases. In order to systematically address this question, we have designed a strategy that discretely introduces differences in secondary structure and hydrophobicity amidst otherwise identical polyamino acids. This strategy will enable us to quantify and compare the affinities of Thioflavin T, Congo Red, and other, incompletely explored, fluorescent dyes for different secondary structural elements and hydrophobic motifs. With this information, we will identify dyes that give the most robust and quantitative information about structural differences among the complex population of oligomeric species present along an aggregation pathway between soluble monomers and amyloid fibrils, and correlate the resulting structural information with differential oligomeric toxicity.

The making of a productivity hotspot in the coastal ocean.

PubMed

Wingfield, Dana K; Peckham, S Hoyt; Foley, David G; Palacios, Daniel M; Lavaniegos, Bertha E; Durazo, Reginaldo; Nichols, Wallace J; Croll, Donald A; Bograd, Steven J

2011-01-01

Highly productive hotspots in the ocean often occur where complex physical forcing mechanisms lead to aggregation of primary and secondary producers. Understanding how hotspots persist, however, requires combining knowledge of the spatio-temporal linkages between geomorphology, physical forcing, and biological responses with the physiological requirements and movement of top predators. Here we integrate remotely sensed oceanography, ship surveys, and satellite telemetry to show how local geomorphology interacts with physical forcing to create a region with locally enhanced upwelling and an adjacent upwelling shadow that promotes retentive circulation, enhanced year-round primary production, and prey aggregation. These conditions provide an area within the upwelling shadow where physiologically optimal water temperatures can be found adjacent to a region of enhanced prey availability, resulting in a foraging hotspot for loggerhead sea turtles (Caretta caretta) off the Baja California peninsula, Mexico. We have identified the set of conditions that lead to a persistent top predator hotspot, which increases our understanding of how highly migratory species exploit productive regions of the ocean. These results will aid in the development of spatially and environmentally explicit management strategies for marine species of conservation concern.

Molecular dynamics simulation studies of caffeine aggregation in aqueous solution.

PubMed

Tavagnacco, Letizia; Schnupf, Udo; Mason, Philip E; Saboungi, Marie-Louise; Cesàro, Attilio; Brady, John W

2011-09-22

Molecular dynamics simulations were carried out on a system of eight independent caffeine molecules in a periodic box of water at 300 K, representing a solution near the solubility limit for caffeine at room temperature, using a newly developed CHARMM-type force field for caffeine in water. Simulations were also conducted for single caffeine molecules in water using two different water models (TIP3P and TIP4P). Water was found to structure in a complex fashion around the planar caffeine molecules, which was not sensitive to the water model used. As expected, extensive aggregation of the caffeine molecules was observed, with the molecules stacking their flat faces against one another like coins, with their methylene groups staggered to avoid steric clashes. A dynamic equilibrum was observed between large n-mers, including stacks with all eight solute molecules, and smaller clusters, with the calculated osmotic coefficient being in acceptable agreement with the experimental value. The insensitivity of the results to water model and the congruence with experimental thermodynamic data suggest that the observed stacking interactions are a realistic representation of the actual association mechanism in aqueous caffeine solutions.

Persistence of soil organic matter in eroding versus depositional landform positions

USGS Publications Warehouse

Berhe, Asmeret Asefaw; Harden, Jennifer W.; Torn, Margaret S.; Kleber, Markus; Burton, Sarah D.; Harte, John

2012-01-01

Soil organic matter (SOM) processes in dynamic landscapes are strongly influenced by soil erosion and sedimentation. We determined the contribution of physical isolation of organic matter (OM) inside aggregates, chemical interaction of OM with soil minerals, and molecular structure of SOM in controlling storage and persistence of SOM in different types of eroding and depositional landform positions. By combining density fractionation with elemental and spectroscopic analyses, we showed that SOM in depositional settings is less transformed and better preserved than SOM in eroding landform positions. However, which environmental factors exert primary control on storage and persistence of SOM depended on the nature of the landform position considered. In an annual grassland watershed, protection of SOM by physical isolation inside aggregates and chemical association of organic matter (complexation) with soil minerals, as assessed by correlation with radiocarbon concentration, were more effective in the poorly drained, lowest-lying depositional landform positions, compared to well-drained landform positions in the upper parts of the watershed. Results of this study demonstrated that processes of soil erosion and deposition are important mechanisms of long-term OM stabilization.

Temperature and carbon assimilation regulate the chlorosome biogenesis in green sulfur bacteria.

PubMed

Tang, Joseph Kuo-Hsiang; Saikin, Semion K; Pingali, Sai Venkatesh; Enriquez, Miriam M; Huh, Joonsuk; Frank, Harry A; Urban, Volker S; Aspuru-Guzik, Alán

2013-09-17

Green photosynthetic bacteria adjust the structure and functionality of the chlorosome-the light-absorbing antenna complex-in response to environmental stress factors. The chlorosome is a natural self-assembled aggregate of bacteriochlorophyll (BChl) molecules. In this study, we report the regulation of the biogenesis of the Chlorobaculum tepidum chlorosome by carbon assimilation in conjunction with temperature changes. Our studies indicate that the carbon source and thermal stress culture of C. tepidum grows slower and incorporates fewer BChl c in the chlorosome. Compared with the chlorosome from other cultural conditions we investigated, the chlorosome from the carbon source and thermal stress culture displays (a) smaller cross-sectional radius and overall size, (b) simplified BChl c homologs with smaller side chains, (c) blue-shifted Qy absorption maxima, and (d) a sigmoid-shaped circular dichroism spectra. Using a theoretical model, we analyze how the observed spectral modifications can be associated with structural changes of BChl aggregates inside the chlorosome. Our report suggests a mechanism of metabolic regulation for chlorosome biogenesis. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effects of pulpotomy using mineral trioxide aggregate on prostaglandin transporter and receptors in rat molars.

PubMed

Ohkura, Naoto; Edanami, Naoki; Takeuchi, Ryosuke; Tohma, Aiko; Ohkura, Mariko; Yoshiba, Nagako; Yoshiba, Kunihiko; Ida-Yonemochi, Hiroko; Ohshima, Hayato; Okiji, Takashi; Noiri, Yuichiro

2017-07-31

Mineral trioxide aggregate (MTA) is a commonly used dental pulp-capping material with known effects in promoting reparative dentinogenesis. However, the mechanism by which MTA induces dentine repair remains unclear. The aim of the present study was to investigate the role of prostaglandin E 2 (PGE 2 ) in dentine repair by examining the localisation and mRNA expression levels of its transporter (Pgt) and two of its receptors (Ep2 and Ep4) in a rat model of pulpotomy with MTA capping. Ep2 expression was detected in odontoblasts, endothelial cells, and nerve fibres in normal and pulpotomised tissues, whereas Pgt and Ep4 were immunolocalised only in the odontoblasts. Moreover, mRNA expression of Slco2a1 (encoding Pgt), Ptger2 (encoding Ep2), and Ptger4 (encoding Ep4) was significantly upregulated in pulpotomised dental pulp and trigeminal ganglia after MTA capping. Our results provide insights into the functions of PGE 2 via Pgt and Ep receptors in the healing dentine/pulp complex and may be helpful in developing new therapeutic targets for dental disease.

Effect of Graphene Oxide on Mechanical Properties of Recycled Mortar

NASA Astrophysics Data System (ADS)

Fang, Changle; Long, Wujian; Wei, Jingjie; Xiao, Bingxu; Yan, Chen

2017-12-01

The use of recycled aggregate as replacement of natural aggregate has increased in recent years in order to reduce the high consumption of natural resources in construction industry. This paper presents an experimental investigation on the effect of graphene oxide (GO) on the mechanical properties of recycled mortar. It is showed that the recycled mortar with GO has a better mechanical properties than the recycled mortar without GO. Microstructural analysis of the recycled mortar with GO showed to have much denser and better crystallization of hydration product.

Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression.

PubMed

Erlejman, Alejandra G; Lagadari, Mariana; Toneatto, Judith; Piwien-Pilipuk, Graciela; Galigniana, Mario D

2014-02-01

The term molecular chaperone was first used to describe the ability of nucleoplasmin to prevent the aggregation of histones with DNA during the assembly of nucleosomes. Subsequently, the name was extended to proteins that mediate the post-translational assembly of oligomeric complexes protecting them from denaturation and/or aggregation. Hsp90 is a 90-kDa molecular chaperone that represents the major soluble protein of the cell. In contrast to most conventional chaperones, Hsp90 functions as a refined sensor of protein function and its principal role in the cell is to facilitate biological activity to properly folded client proteins that already have a preserved tertiary structure. Consequently, Hsp90 is related to basic cell functions such as cytoplasmic transport of soluble proteins, translocation of client proteins to organelles, and regulation of the biological activity of key signaling factors such as protein kinases, ubiquitin ligases, steroid receptors, cell cycle regulators, and transcription factors. A growing amount of evidence links the protective action of this molecular chaperone to mechanisms related to posttranslational modifications of soluble nuclear factors as well as histones. In this article, we discuss some aspects of the regulatory action of Hsp90 on transcriptional regulation and how this effect could have impacted genetic assimilation mechanism in some organisms. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanisms of Ricin Toxin Neutralization Revealed through Engineered Homodimeric and Heterodimeric Camelid Antibodies.

PubMed

Herrera, Cristina; Tremblay, Jacqueline M; Shoemaker, Charles B; Mantis, Nicholas J

2015-11-13

Novel antibody constructs consisting of two or more different camelid heavy-chain only antibodies (VHHs) joined via peptide linkers have proven to have potent toxin-neutralizing activity in vivo against Shiga, botulinum, Clostridium difficile, anthrax, and ricin toxins. However, the mechanisms by which these so-called bispecific VHH heterodimers promote toxin neutralization remain poorly understood. In the current study we produced a new collection of ricin-specific VHH heterodimers, as well as VHH homodimers, and characterized them for their ability neutralize ricin in vitro and in vivo. We demonstrate that the VHH heterodimers, but not homodimers were able to completely protect mice against ricin challenge, even though the two classes of antibodies (heterodimers and homodimers) had virtually identical affinities for ricin holotoxin and similar IC50 values in a Vero cell cytotoxicity assay. The VHH heterodimers did differ from the homodimers in their ability to promote toxin aggregation in solution, as revealed through analytical ultracentrifugation. Moreover, the VHH heterodimers that were most effective at promoting ricin aggregation in solution were also the most effective at blocking ricin attachment to cell surfaces. Collectively, these data suggest that heterodimeric VHH-based neutralizing agents may function through the formation of antibody-toxin complexes that are impaired in their ability to access host cell receptors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Modes of Diffusion of Cholera Toxin Bound to GM1 on Live Cell Membrane by Image Mean Square Displacement Analysis

PubMed Central

Moens, Pierre D.J.; Digman, Michelle A.; Gratton, Enrico

2015-01-01

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. PMID:25809257

Modes of diffusion of cholera toxin bound to GM1 on live cell membrane by image mean square displacement analysis.

PubMed

Moens, Pierre D J; Digman, Michelle A; Gratton, Enrico

2015-03-24

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Evaluating load transfer restoration, districts 1 and 3

DOT National Transportation Integrated Search

2002-07-01

Since 1950, concrete pavements in California have been constructed without dowel bars in the transverse joints, Consequently, aggregate interlock has been the primary mechanism for load transfer across adjacent slabs. As the pavements age, the aggreg...

Influence of Aggregate Coated with Modified Sulfur on the Properties of Cement Concrete

PubMed Central

Lee, Swoo-Heon; Hong, Ki-Nam; Park, Jae-Kyu; Ko, Jung

2014-01-01

This paper proposes the mixing design of concrete having modified sulfur-coated aggregate (MSCA) to enhance the durability of Portland cement concrete. The mechanical properties and durability of the proposed MSCA concrete were evaluated experimentally. Melting-modified sulfur was mixed with aggregate in order to coat the aggregate surface at a speed of 20 rpm for 120 s. The MSCA with modified sulfur corresponding to 5% of the cement weight did not significantly affect the flexural strength in a prism concrete beam specimen, regardless of the water-cement ratio (W/C). However, a dosage of more than 7.5% decreased the flexural strength. On the other hand, the MSCA considerably improved the resistance to the sulfuric acid and the freezing-thawing, regardless of the sulfur dosage in the MSCA. The coating modified sulfur of 5% dosage consequently led to good results for the mechanical properties and durability of MSCA concrete. PMID:28788703

Realignment of Nanocrystal Aggregates into Single Crystals as a Result of Inherent Surface Stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Zhaoming; Pan, Haihua; Zhu, Genxing

2016-07-19

Assembly of nanoparticles building blocks during single crystal growth is widely observed in both natural and synthetic environments. Although this form of non-classical crystallization is generally described by oriented attachment, random aggregation of building blocks leading to single crystal products is also observed, but the mechanism of crystallographic realignment is unknown. We herein reveal that random attachment during aggregation-based growth initially produces a non-oriented growth front. Subsequent evolution of the orientation is driven by the inherent surface stress applied by the disordered surface layer and results in single crystal formation via grain boundary migration. This mechanism is corroborated by measurementsmore » of orientation rate vs external stress, demonstrating a predictive relationship between the two. These findings advance our understanding of aggregation-based growth of natural minerals by nanocrystals, and suggest an approach to material synthesis that takes advantage of stress induced co-alignment.« less

Ballistic aggregation in systems of inelastic particles: Cluster growth, structure, and aging

NASA Astrophysics Data System (ADS)

Paul, Subhajit; Das, Subir K.

2017-07-01

We study far-from-equilibrium dynamics in models of freely cooling granular gas and ballistically aggregating compact clusters. For both the cases, from event-driven molecular dynamics simulations, we have presented detailed results on structure and dynamics in space dimensions d =1 and 2. Via appropriate analyses it has been confirmed that the ballistic aggregation mechanism applies in d =1 granular gases as well. Aging phenomena for this mechanism, in both the dimensions, have been studied via the two-time density autocorrelation function. This quantity is demonstrated to exhibit scaling property similar to that in the standard phase transition kinetics. The corresponding functional forms have been quantified and the outcomes have been discussed in connection with the structural properties. Our results on aging establish a more complete equivalence between the granular gas and the ballistic aggregation models in d =1 .

Molecular aggregation of humic substances

USGS Publications Warehouse

Wershaw, R. L.

1999-01-01

Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

Mechanical and Physical Properties of Polyester Polymer Concrete Using Recycled Aggregates from Concrete Sleepers

PubMed Central

Carrión, Francisco; Montalbán, Laura; Real, Julia I.

2014-01-01

Currently, reuse of solid waste from disused infrastructures is an important environmental issue to study. In this research, polymer concrete was developed by mixing orthophthalic unsaturated polyester resin, artificial microfillers (calcium carbonate), and waste aggregates (basalt and limestone) coming from the recycling process of concrete sleepers. The variation of the mechanical and physical properties of the polymer concrete (compressive strength, flexural strength, modulus of elasticity, density, and water absorption) was analyzed based on the modification of different variables: nature of the recycled aggregates, resin contents (11 wt%, 12 wt%, and 13 wt%), and particle-size distributions of microfillers used. The results show the influence of these variables on mechanical performance of polymer concrete. Compressive and flexural strength of recycled polymer concrete were improved by increasing amount of polyester resin and by optimizing the particle-size distribution of the microfillers. Besides, the results show the feasibility of developing a polymer concrete with excellent mechanical behavior. PMID:25243213

Mechanical and physical properties of polyester polymer concrete using recycled aggregates from concrete sleepers.

PubMed

Carrión, Francisco; Montalbán, Laura; Real, Julia I; Real, Teresa

2014-01-01

Currently, reuse of solid waste from disused infrastructures is an important environmental issue to study. In this research, polymer concrete was developed by mixing orthophthalic unsaturated polyester resin, artificial microfillers (calcium carbonate), and waste aggregates (basalt and limestone) coming from the recycling process of concrete sleepers. The variation of the mechanical and physical properties of the polymer concrete (compressive strength, flexural strength, modulus of elasticity, density, and water absorption) was analyzed based on the modification of different variables: nature of the recycled aggregates, resin contents (11 wt%, 12 wt%, and 13 wt%), and particle-size distributions of microfillers used. The results show the influence of these variables on mechanical performance of polymer concrete. Compressive and flexural strength of recycled polymer concrete were improved by increasing amount of polyester resin and by optimizing the particle-size distribution of the microfillers. Besides, the results show the feasibility of developing a polymer concrete with excellent mechanical behavior.

Reversible Self-Assembly of Water-Soluble Gold(I) Complexes.

PubMed

Aguiló, Elisabet; Moro, Artur J; Gavara, Raquel; Alfonso, Ignacio; Pérez, Yolanda; Zaccaria, Francesco; Guerra, Célia Fonseca; Malfois, Marc; Baucells, Clara; Ferrer, Montserrat; Lima, João Carlos; Rodríguez, Laura

2018-02-05

The reaction of the gold polymers containing bipyridyl and terpyridyl units, [Au(C≡CC 15 H 10 N 3 )] n and [Au(C≡CC 10 H 7 N 2 )] n , with the water-soluble phosphines 1,3,5-triaza-7-phosphatricyclo[3.3.1.13.7]decane and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane gives rise to the formation of four gold(I) alkynyl complexes that self-assemble in water (H 2 O) and dimethyl sulfoxide (DMSO), through different intermolecular interactions, with an impact on the observed luminescence displayed by the supramolecular assemblies. A detailed analysis carried out by NMR studies performed in different DMSO/deuterated H 2 O mixtures indicates the presence of two different assembly modes in the aggregates: (i) chain assemblies, which are based mainly on aurophilic interactions, and (ii) stacked assemblies, which are based on Au···π and π···π interactions. These different supramolecular environments can also be detected by their intrinsic optical properties (differences in absorption and emission spectra) and are predicted by the changes in the relative binding energy from density functional theory calculations carried out in DMSO and H 2 O. Small-angle X-ray scattering (SAXS) experiments performed in the same mixture of solvents are in agreement with the formation of aggregates in all cases. The aromatic units chosen, bipyridine and terpyridine, allow the use of external stimuli to reversibly change the aggregation state of the supramolecular assemblies. Interaction with the Zn 2+ cation is observed to disassemble the aggregates, while encapsulating agents competing for Zn 2+ complexation revert the process to the aggregation stage, as verified by SAXS and NMR. The adaptive nature of the supramolecular assemblies to the metal-ion content is accompanied by significant changes in the absorption and emission spectra, signaling the aggregation state and also the content on Zn 2+ .

Synchrotron-based micro and nanotomographic investigations of soil aggregate microbial and pore structure

NASA Astrophysics Data System (ADS)

Kemner, K. M.; O'Brien, S.; Whiteside, M. D.; Sholto-Douglas, D.; Antipova, O.; Bailey, V.; Boyanov, M.; Dohnalkova, A.; Gursoy, D.; Kovarik, L.; Lai, B.; Roehrig, C.; Vogt, S.

2017-12-01

Soil is a highly complex network of pore spaces, minerals, and organic matter (e.g., roots, fungi, and bacteria), making it physically heterogeneous over nano- to macro-scales. Such complexity arises from feedbacks between physical processes and biological activity that generate a dynamic, self-organizing 3D complex. Since we first demonstrated the utility of synchrotron-based transmission tomography to image internal soil aggregate structure [Kemner et al., 1998], we and many other researchers have made use of and have advanced the application of this technique. However, our understanding of how microbes and microbial metabolism are distributed throughout soil aggregates is limited, because no technique is available to image the soil pore network and the life that inhabits it. X-ray transmission microtomography can provide highly detailed 3D renderings of soil structure but cannot distinguish cells from other electron-light material such as air or water. However, the use of CdSe quantum dots (QDs) as a reporter of bacterial presence enables us to overcome this constraint, instilling bacterial cells with enough contrast to detect them and their metabolic functions in their opaque soil habitat, with hard x-rays capable of penetrating 3D soil structures at high resolution. Previous transmission tomographic imaging of soil aggregates with high energy synchrotron x-rays has demonstrated 700 nm3 voxel spatial resolution. These and recent results from nanotomographic x-ray transmission imaging of soil aggregates with 30 nm3 voxel resolution will be presented. In addition, results of submicron voxel-sized x-ray fluorescence 3D imaging to determine microbial distributions within soil aggregates and the critical role to be played by the upgrade of the Advanced Photon Source for 100-1000X increases in hard x-ray brilliance will also be presented. *Kemner, et al., SPIE 3449, 45-53, 1998

Minimal Model of Quantum Kinetic Clusters for the Energy-Transfer Network of a Light-Harvesting Protein Complex.

PubMed

Wu, Jianlan; Tang, Zhoufei; Gong, Zhihao; Cao, Jianshu; Mukamel, Shaul

2015-04-02

The energy absorbed in a light-harvesting protein complex is often transferred collectively through aggregated chromophore clusters. For population evolution of chromophores, the time-integrated effective rate matrix allows us to construct quantum kinetic clusters quantitatively and determine the reduced cluster-cluster transfer rates systematically, thus defining a minimal model of energy-transfer kinetics. For Fenna-Matthews-Olson (FMO) and light-havrvesting complex II (LCHII) monomers, quantum Markovian kinetics of clusters can accurately reproduce the overall energy-transfer process in the long-time scale. The dominant energy-transfer pathways are identified in the picture of aggregated clusters. The chromophores distributed extensively in various clusters can assist a fast and long-range energy transfer.

Granule Formation Mechanisms within an Aerobic Wastewater System for Phosphorus Removal▿ †

PubMed Central

Barr, Jeremy J.; Cook, Andrew E.; Bond, Phillip L.

2010-01-01

Granular sludge is a novel alternative for the treatment of wastewater and offers numerous operational and economic advantages over conventional floccular-sludge systems. The majority of research on granular sludge has focused on optimization of engineering aspects relating to reactor operation with little emphasis on the fundamental microbiology. In this study, we hypothesize two novel mechanisms for granule formation as observed in three laboratory scale sequencing batch reactors operating for biological phosphorus removal and treating two different types of wastewater. During the initial stages of granulation, two distinct granule types (white and yellow) were distinguished within the mixed microbial population. White granules appeared as compact, smooth, dense aggregates dominated by 97.5% “Candidatus Accumulibacter phosphatis,” and yellow granules appeared as loose, rough, irregular aggregates with a mixed microbial population of 12.3% “Candidatus Accumulibacter phosphatis” and 57.9% “Candidatus Competibacter phosphatis,” among other bacteria. Microscopy showed white granules as homogeneous microbial aggregates and yellow granules as segregated, microcolony-like aggregates, with phylogenetic analysis suggesting that the granule types are likely not a result of strain-associated differences. The microbial community composition and arrangement suggest different formation mechanisms occur for each granule type. White granules are hypothesized to form by outgrowth from a single microcolony into a granule dominated by one bacterial type, while yellow granules are hypothesized to form via multiple microcolony aggregation into a microcolony-segregated granule with a mixed microbial population. Further understanding and application of these mechanisms and the associated microbial ecology may provide conceptual information benefiting start-up procedures for full-scale granular-sludge reactors. PMID:20851963

Amyloid fibril formation by the chain B subunit of monellin occurs by a nucleation-dependent polymerization mechanism.

PubMed

Sabareesan, A T; Udgaonkar, Jayant B

2014-02-25

Proteins possessing very different structures, or even no structure, form amyloid fibrils that are very similar in internal structure. This suggests that the mechanisms by which amyloid fibrils form might be very similar, irrespective of whether the fibrils are associated with disease or with normal cellular function, or even if they have no physiological importance. In this context, it is important to have a model protein system whose amyloid fibril formation is robust in its reproducibility, which can reveal the fundamentals of the amyloid fibril reaction that may be applicable to all proteins. In this study, the aggregation mechanism of amyloid fibril formation by chain B of the heterodimeric protein monellin has been elucidated in detail. It is shown that the aggregation reaction meets all the stringent kinetic criteria of a homogeneous nucleation-dependent polymerization mechanism, which is valid over a wide range of protein concentrations. Quantitative analyses of the kinetic data using one approach based on features of the entire kinetic curve, and another based on only the initial rate of aggregation, indicate that the thermodynamic nucleus is a dimer. Spherical oligomers are observed by atomic force microscopy to form transiently early during fibril formation but are off-pathway to the direct fibril formation pathway. It is shown that amyloid fibril formation can be prevented by the addition of chain A of monellin at early stages of chain B aggregation: the two free chains combine to form native monellin, which leads to the dissociation of early aggregates.

Operational Plasticity Enables Hsp104 to Disaggregate Diverse Amyloid and Non-Amyloid Clients

PubMed Central

DeSantis, Morgan E.; Leung, Eunice H.; Sweeny, Elizabeth A.; Jackrel, Meredith E.; Cushman-Nick, Mimi; Neuhaus-Follini, Alexandra; Vashist, Shilpa; Sochor, Matthew A.; Knight, M. Noelle; Shorter, James

2012-01-01

Summary It is not understood how Hsp104, a hexameric AAA+ ATPase from yeast, disaggregates diverse structures including stress-induced aggregates, prions, and α-synuclein conformers connected to Parkinson disease. Here, we establish that Hsp104 hexamers adapt different mechanisms of intersubunit collaboration to disaggregate stress-induced aggregates versus amyloid. To resolve disordered aggregates, Hsp104 subunits collaborate non-co-operatively via probabilistic substrate binding and ATP hydrolysis. To disaggregate amyloid, several subunits co-operatively engage substrate and hydrolyze ATP. Importantly, Hsp104 variants with impaired intersubunit communication dissolve disordered aggregates but not amyloid. Unexpectedly, prokaryotic ClpB subunits collaborate differently than Hsp104 and couple probabilistic substrate binding to cooperative ATP hydrolysis, which enhances disordered aggregate dissolution but sensitizes ClpB to inhibition and diminishes amyloid disaggregation. Finally, we establish that Hsp104 hexamers deploy more subunits to disaggregate Sup35 prion strains with more stable ‘cross-β’ cores. Thus, operational plasticity enables Hsp104 to robustly dissolve amyloid and non-amyloid clients, which impose distinct mechanical demands. PMID:23141537

Is It Possible To Fabricate a Nanocomposite with Excellent Mechanical Property Using Unmodified Inorganic Nanoparticles Directly?

PubMed

Zhang, Chunhua; Xia, Liangjun; Lyu, Pei; Wang, Yun; Li, Chen; Xiao, Xingfang; Dai, Fangyin; Xu, Weilin; Liu, Xin; Deng, Bo

2018-05-09

Unmodified ZrO 2 nanoparticles (ZDNPs) are used for the enhancement of polyurethane (PU) films. Optimized strain and toughness of PU/ZDNP nanocomposite at 9.09 wt % ZDNPs are up to 2714.6%, and 280.8 MJ m -3 , respectively. The unique bimodal ZDNP aggregate size distribution which exploits both interfacial positively and negatively toughening mechanisms accounts mainly for the excellent mechanical property of PU/ZDNP nanocomposite. The dependence of different toughening mechanisms on three sizes of ZDNP aggregates is summarized. These findings provide a new avenue for the industrial production of nanocomposites at low cost without surface modification of inorganic nanoparticles.

Flocculation of colloidal clay by bacterial polysaccharides: effect of macromolecule charge and structure.

PubMed

Labille, J; Thomas, F; Milas, M; Vanhaverbeke, C

2005-04-01

The molecular mechanism of montmorillonite flocculation by bacterial polysaccharides was investigated, with special emphasis on the effect of carboxylic charges in the macromolecules on the mechanisms of interaction with the clay surface. An indirect way to quantify the energy of interaction was used, by comparing the flocculation ability of variously acidic polysaccharides. Data on tensile strength of aggregates in diluted suspension were collected by timed size measurements in the domain 0.1-600 microm, using laser diffraction. The flow behavior of settled aggregates was studied by rheology measurements. Flocculation of colloidal clay suspension by polysaccharides requires cancelling of the electrostatic repulsions by salts, which allows approach of clay surfaces close enough to be bridged by adsorbing macromolecules. The amount of acidic charges of the polysaccharides, and especially their location in the molecular structure, governs the bridging mechanism and the resulting tensile strength of the aggregates. The exposure of carboxylate groups located on side chains strongly promotes flocculation. In turn, charges located on the backbone of the polysaccharide are less accessible to interaction, and the flocculation ability of such polysaccharides is lowered. Measurements at different pH indicate that adsorption of acidic polysaccharides occurs via electrostatic interactions on the amphoteric edge surface of clay platelets, whereas neutral polysaccharides rather adsorb via weak interactions. Increased tensile strength in diluted aggregates due to strong surface interactions results in proportionally increased viscosity of the concentrated aggregates.

Feedbacks Between Soil Structure and Microbial Activities in Soil

NASA Astrophysics Data System (ADS)

Bailey, V. L.; Smith, A. P.; Fansler, S.; Varga, T.; Kemner, K. M.; McCue, L. A.

2017-12-01

Soil structure provides the physical framework for soil microbial habitats. The connectivity and size distribution of soil pores controls the microbial access to nutrient resources for growth and metabolism. Thus, a crucial component of soil research is how a soil's three-dimensional structure and organization influences its biological potential on a multitude of spatial and temporal scales. In an effort to understand microbial processes at scale more consistent with a microbial community, we have used soil aggregates as discrete units of soil microbial habitats. Our research has shown that mean pore diameter (x-ray computed tomography) of soil aggregates varies with the aggregate diameter itself. Analyzing both the bacterial composition (16S) and enzyme activities of individual aggregates showed significant differences in the relative abundances of key members the microbial communities associated with high enzyme activities compared to those with low activities, even though we observed no differences in the size of the biomass, nor in the overall richness or diversity of these communities. We hypothesize that resources and substrates have stimulated key populations in the aggregates identified as highly active, and as such, we conducted further research that explored how such key populations (i.e. fungal or bacterial dominated populations) alter pathways of C accumulation in aggregate size domains and microbial C utilization. Fungi support and stabilize soil structure through both physical and chemical effects of their hyphal networks. In contrast, bacterial-dominated communities are purported to facilitate micro- and fine aggregate stabilization. Here we quantify the direct effects fungal versus bacterial dominated communities on aggregate formation (both the rate of aggregation and the quality, quantity and distribution of SOC contained within aggregates). A quantitative understanding of the different mechanisms through which fungi or bacteria shape aggregate formation could alter how we currently treat our predictions of soil biogeochemistry. Current predictions are largely site- or biome-specific; quantitative mechanisms could underpin "rules" that operate at the pore-scale leading to more robust, mechanistic models.

Supramolecular aggregates of metallo-organic acids with stilbazoles. Formation of columnar mesophases and Langmuir films.

PubMed

Domínguez, Cristina; Donnio, Bertrand; Coco, Silverio; Espinet, Pablo

2013-11-28

Supramolecular metal complexes formed through hydrogen bonding between tris(3,4,5-decyloxy)stilbazole and several metallo-organic acids of the type [Au(R)(CNC6H4CO2H)] (R = C6F5, C6F4OC10H21), [cis-[MCl2(CNC6H4COOH)2] and [trans-[MI2(CNC6H4COOH)2] (M = Pd, Pt) have been synthesized. All the supramolecular palladium and platinum polycatenar aggregates display a hexagonal columnar mesophase at temperatures close to room temperature. Most of the supramolecular trisalkoxystilbazole complexes exhibit luminescent behaviour. Aggregates of [Au(C6F4OC10H21)(CNC6H4CO2H)] and [trans-[MI2(CNC6H4COOH)2] (M = Pd, Pt) form stable Langmuir films at the air-water interface.

Colorimetric As (V) detection based on S-layer functionalized gold nanoparticles.

PubMed

Lakatos, Mathias; Matys, Sabine; Raff, Johannes; Pompe, Wolfgang

2015-11-01

Herein, we present simple and rapid colorimetric and UV/VIS spectroscopic methods for detecting anionic arsenic (V) complexes in aqueous media. The methods exploit the aggregation of S-layer-functionalized spherical gold nanoparticles of sizes between 20 and 50 nm in the presence of arsenic species. The gold nanoparticles were functionalized with oligomers of the S-layer protein of Lysinibacillus sphaericus JG-A12. The aggregation of the nanoparticles results in a color change from burgundy-red for widely dispersed nanoparticles to blue for aggregated nanoparticles. A detailed signal analysis was achieved by measuring the shift of the particle plasmon resonance signal with UV/VIS spectroscopy. To further improve signal sensitivity, the influence of larger nanoparticles was tested. In the case of 50 nm gold nanoparticles, a concentration of the anionic arsenic (V) complex lower than 24 ppb was detectable. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of multivalency in the association kinetics of patchy particle complexes.

PubMed

Newton, Arthur C; Groenewold, Jan; Kegel, Willem K; Bolhuis, Peter G

2017-06-21

Association and dissociation of particles are elementary steps in many natural and technological relevant processes. For many such processes, the presence of multiple binding sites is essential. For instance, protein complexes and regular structures such as virus shells are formed from elementary building blocks with multiple binding sites. Here we address a fundamental question concerning the role of multivalency of binding sites in the association kinetics of such complexes. Using single replica transition interface sampling simulations, we investigate the influence of the multivalency on the binding kinetics and the association mechanism of patchy particles that form polyhedral clusters. When the individual bond strength is fixed, the kinetics naturally is very dependent on the multivalency, with dissociation rate constants exponentially decreasing with the number of bonds. In contrast, we find that when the total bond energy per particle is kept constant, association and dissociation rate constants turn out rather independent of multivalency, although of course still very dependent on the total energy. The association and dissociation mechanisms, however, depend on the presence and nature of the intermediate states. For instance, pathways that visit intermediate states are less prevalent for particles with five binding sites compared to the case of particles with only three bonds. The presence of intermediate states can lead to kinetic trapping and malformed aggregates. We discuss implications for natural forming complexes such as virus shells and for the design of artificial colloidal patchy particles.

The role of multivalency in the association kinetics of patchy particle complexes

NASA Astrophysics Data System (ADS)

Newton, Arthur C.; Groenewold, Jan; Kegel, Willem K.; Bolhuis, Peter G.

2017-06-01

Association and dissociation of particles are elementary steps in many natural and technological relevant processes. For many such processes, the presence of multiple binding sites is essential. For instance, protein complexes and regular structures such as virus shells are formed from elementary building blocks with multiple binding sites. Here we address a fundamental question concerning the role of multivalency of binding sites in the association kinetics of such complexes. Using single replica transition interface sampling simulations, we investigate the influence of the multivalency on the binding kinetics and the association mechanism of patchy particles that form polyhedral clusters. When the individual bond strength is fixed, the kinetics naturally is very dependent on the multivalency, with dissociation rate constants exponentially decreasing with the number of bonds. In contrast, we find that when the total bond energy per particle is kept constant, association and dissociation rate constants turn out rather independent of multivalency, although of course still very dependent on the total energy. The association and dissociation mechanisms, however, depend on the presence and nature of the intermediate states. For instance, pathways that visit intermediate states are less prevalent for particles with five binding sites compared to the case of particles with only three bonds. The presence of intermediate states can lead to kinetic trapping and malformed aggregates. We discuss implications for natural forming complexes such as virus shells and for the design of artificial colloidal patchy particles.

Environmental Variability, Bowhead Whale Distributions, and Inupiat Subsistence Whaling in the Coastal Arctic Ocean

NASA Astrophysics Data System (ADS)

Ashjian, C. J.; Campbell, R. G.; George, J. C.; Moore, S. E.; Okkonen, S. R.; Sherr, B. F.; Sherr, E. B.

2006-12-01

The annual migration of bowhead whales (Balaena mysticetus) past Barrow, Alaska has provided subsistence hunting opportunities to Native whalers for centuries. Bowheads regularly feed along the Arctic coast near Barrow in autumn, presumably to utilize recurrent aggregations of their zooplankton prey (e.g., copepods, euphausiids). Oceanographic field-sampling on the narrow continental shelf near Barrow and in Elson Lagoon was conducted during mid-August to mid-September of 2005 and 2006 to describe the different water mass types and plankton communities, to identify exchange of water and material between the shelf and lagoon and offshore, and to identify biological and physical mechanisms of plankton aggregation. High spatial resolution profiles of temperature, salinity, fluorescence, optical backscatter, and C-DOM were collected using an Acrobat undulating towed vehicle in the lagoon and across the shelf from near-shore to the ~150 m isobath. Discrete sampling for nutrients, chlorophyll a, and phytoplankton, and microzooplankton and mesozooplankton abundance and composition was conducted in distinct water types and across frontal boundaries identified from the high-resolution data. The distributions of bowhead whales were documented using aerial surveys. Inter-annual and shorter-term (days to weeks) variability in the distribution of water masses and intrinsic biological properties was observed. Distinct hydrographic and biological-chemical regions were located across the shelf that may contribute to the formation of bowhead whale prey aggregations. The lagoon system is an important interface between the ocean and land and may be critical to the formation of nearshore bowhead whale prey aggregations. Results from the field sampling will be coupled to biological-physical modeling and retrospective analyses to understand the response of this complex environment-whale-human system to climate variability.

Ultra-Fine Scale Spatially-Integrated Mapping of Habitat and Occupancy Using Structure-From-Motion

PubMed Central

McDowall, Philip; Lynch, Heather J.

2017-01-01

Organisms respond to and often simultaneously modify their environment. While these interactions are apparent at the landscape extent, the driving mechanisms often occur at very fine spatial scales. Structure-from-Motion (SfM), a computer vision technique, allows the simultaneous mapping of organisms and fine scale habitat, and will greatly improve our understanding of habitat suitability, ecophysiology, and the bi-directional relationship between geomorphology and habitat use. SfM can be used to create high-resolution (centimeter-scale) three-dimensional (3D) habitat models at low cost. These models can capture the abiotic conditions formed by terrain and simultaneously record the position of individual organisms within that terrain. While coloniality is common in seabird species, we have a poor understanding of the extent to which dense breeding aggregations are driven by fine-scale active aggregation or limited suitable habitat. We demonstrate the use of SfM for fine-scale habitat suitability by reconstructing the locations of nests in a gentoo penguin colony and fitting models that explicitly account for conspecific attraction. The resulting digital elevation models (DEMs) are used as covariates in an inhomogeneous hybrid point process model. We find that gentoo penguin nest site selection is a function of the topography of the landscape, but that nests are far more aggregated than would be expected based on terrain alone, suggesting a strong role of behavioral aggregation in driving coloniality in this species. This integrated mapping of organisms and fine scale habitat will greatly improve our understanding of fine-scale habitat suitability, ecophysiology, and the complex bi-directional relationship between geomorphology and habitat use. PMID:28076351

Structure–Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders

PubMed Central

Rahimi, F.; Shanmugam, A.; Bitan, G.

2010-01-01

Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other organ-specific diseases, such as dialysis-related amyloidosis and type-2 diabetes mellitus, also are characterized by deposition of aberrantly folded, insoluble proteins. It is debated whether the hallmark pathologic lesions are causative. Substantial evidence suggests that these aggregates are the end state of aberrant protein folding whereas the actual culprits likely are transient, pre-fibrillar assemblies preceding the aggregates. In the context of neurodegenerative amyloidoses, the proteinaceous aggregates may eventuate as potentially neuroprotective sinks for the neurotoxic, oligomeric protein assemblies. The pre-fibrillar, oligomeric assemblies are believed to initiate the pathogenic mechanisms that lead to synaptic dysfunction, neuronal loss, and disease-specific regional brain atrophy. The amyloid β-protein (Aβ), which is believed to cause Alzheimer's disease (AD), is considered an archetypal amyloidogenic protein. Intense studies have led to nominal, functional, and structural descriptions of oligomeric Aβ assemblies. However, the dynamic and metastable nature of Aβ oligomers renders their study difficult. Different results generated using different methodologies under different experimental settings further complicate this complex area of research and identification of the exact pathogenic assemblies in vivo seems daunting. Here we review structural, functional, and biological experiments used to produce and study pre-fibrillar Aβ assemblies, and highlight similar studies of proteins involved in related diseases. We discuss challenges that contemporary researchers are facing and future research prospects in this demanding yet highly important field. PMID:18537546

Understanding curcumin-induced modulation of protein aggregation.

PubMed

Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

2017-07-01

Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

Counter effect of sucrose on ethanol-induced aggregation of protein.

PubMed

Yadav, Jay Kant; Chandani, N; Pande Prajakt, P R; Chauhan, Jyoti Bala

2010-12-01

The present paper is an attempt to study the mechanism of ethanol induced aggregation of chicken egg albumin and to stabilize the protein against ethanol induced aggregation. The protein aggregation was determined by monitoring the light scattering of protein aggregates spectrophotometrically. The protein undergoes certain structural changes in water-ethanol solution and the degree of aggregation was found to be linearly depending upon the concentration of alcohol used. The intrinsic fluorescence study showed a large blue shift in the λ(max) (16 nm) in the presence of 50% ethanol. The ANS fluorescence intensity was found to be gradually increasing with increasing concentration of ethanol. This indicates an increase in the hydrophobic cluster on the protein surface and as a result the hydrophobic interaction is the major driving force for the aggregate formation. Addition of sucrose significantly reduced the ethanol-induced protein aggregation. In presence of 50% sucrose the ethanol the aggregation was reduced to 5%. The study reveals that addition of sucrose brings out changes in the solvent distribution and prevents the structural changes in protein which lead the aggregation.

Use of wastes derived from earthquakes for the production of concrete masonry partition wall blocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao Zhao; Faculty of Architecture, Civil Engineering and Environment Engineering and Mechanics, Sichuan University; Ling, Tung-Chai

2011-08-15

Highlights: > Solved the scientific and technological challenges impeding use of waste rubble derived from earthquake, by providing an alternative solution of recycling the waste in moulded concrete block products. > Significant requirements for optimum integration on the utilization of the waste aggregates in the production of concrete blocks are investigated. > A thorough understanding of the mechanical properties of concrete blocks made with waste derived from earthquake is reported. - Abstract: Utilization of construction and demolition (C and D) wastes as recycled aggregates in the production of concrete and concrete products have attracted much attention in recent years. However,more » the presence of large quantities of crushed clay brick in some the C and D waste streams (e.g. waste derived collapsed masonry buildings after an earthquake) renders the recycled aggregates unsuitable for high grade use. One possibility is to make use of the low grade recycled aggregates for concrete block production. In this paper, we report the results of a comprehensive study to assess the feasibility of using crushed clay brick as coarse and fine aggregates in concrete masonry block production. The effects of the content of crushed coarse and fine clay brick aggregates (CBA) on the mechanical properties of non-structural concrete block were quantified. From the experimental test results, it was observed that incorporating the crushed clay brick aggregates had a significant influence on the properties of blocks. The hardened density and drying shrinkage of the block specimens decreased with an increase in CBA content. The use of CBA increased the water absorption of block specimens. The results suggested that the amount of crushed clay brick to be used in concrete masonry blocks should be controlled at less than 25% (coarse aggregate) and within 50-75% for fine aggregates.« less