SciCombinator

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Concept: Aggregate

202

Bed bugs have shown a recent and rapid global expansion that has been suggested to be caused by cheap air travel. How a small, flightless and anachoretic insect that hides within its host’s sleeping area manages to travel long distances is not yet clear. Bed bugs are attracted to the odour of sleeping humans and we suggest that soiled clothing may present a similarly attractive cue, allowing bed bugs to ‘hitch-hike’ around the world after aggregating in the laundry bags of travellers. We show that (1) soiled clothing is significantly more attractive than clean clothing to active bed bugs moving within a bedroom sized arena and (2) elevation of CO2 to a level that simulates human occupancy in the same arena appears to initiate search behaviour rather than direct it. Our results show, for the first time, how leaving worn clothing exposed in sleeping areas when travelling can be exploited by bed bugs to facilitate passive dispersal.

Concepts: Human, Aggregate, Hemiptera, Suggestion, Travel, Traveler, Active, Bedbug

169

The identities of toxic aggregate species in Huntington’s disease pathogenesis remain ambiguous. While polyQ-expanded huntingtin (Htt) is known to accumulate in compact inclusion bodies inside neurons, this is widely thought to be a protective coping response that sequesters misfolded conformations or aggregated states of the mutated protein. To define the spatial distributions of fluorescently-labeled Htt-exon1 species in the cell model PC12m, we employed highly sensitive single-molecule super-resolution fluorescence imaging. In addition to inclusion bodies and the diffuse pool of monomers and oligomers, fibrillar aggregates ~100 nm in diameter and up to ~1-2 µm in length were observed for pathogenic polyQ tracts (46 and 97 repeats) after targeted photo-bleaching of the inclusion bodies. These short structures bear a striking resemblance to fibers described in vitro. Definition of the diverse Htt structures in cells will provide an avenue to link the impact of therapeutic agents to aggregate populations and morphologies.

Concepts: DNA, Protein, Gene, Aggregate, Oligomer, Huntington's disease, Huntingtin, Trinucleotide repeat disorder

166

Aggregation of TAR DNA-binding protein 43 (TDP-43) is a pathological signature of amyotrophic lateral sclerosis (ALS). Although accumulating evidence suggests the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy, it remains unclear how native TDP-43 is converted to pathogenic forms. To elucidate the role of homeostasis of RRM1 structure in ALS pathogenesis, conformations of RRM1 under high pressure were monitored by NMR. We first found that RRM1 was prone to aggregation and had three regions showing stable chemical shifts during misfolding. Moreover, mass-spectrometric analysis of aggregated RRM1 revealed that one of the regions was located on protease-resistant β-strands containing two cysteines (C173 and C175), indicating that this region served as a core assembly interface in RRM1 aggregation. Although a fraction of RRM1 aggregates comprised disulfide-bonded oligomers, the substitution of cysteine(s) to serine(s) (C/S) resulted in unexpected acceleration of amyloid fibrils of RRM1 and disulfide-independent aggregate formation of full-length TDP-43. Notably, TDP-43 aggregates with RRM1-C/S required C-terminus, and replicated cytopathologies of ALS, including mislocalization, impaired RNA splicing, ubiquitination, phosphorylation, and motor neuron toxicity. Furthermore, RRM1-C/S accentuated inclusions of familial ALS-linked TDP-43 mutants in C-terminus. The relevance of RRM1-C/S-induced TDP-43 aggregates in ALS pathogenesis was verified by immunolabeling of inclusions of ALS patients and cultured cells overexpressing the RRM1-C/S TDP-43 with antibody targeting a misfolding-relevant regions. Our results indicate that cysteines in RRM1 crucially govern the conformation of TDP-43, and aberrant self-assembly of RRM1 at amyloidogenic regions contributes to pathogenic conversion of TDP-43 in ALS.

Concepts: DNA, Protein, Amyloid, Amyotrophic lateral sclerosis, Aggregate, Aggregate data, RNA splicing, Proteopathy

83

Objective: In contrast to proposals that physical activity (PA) can be a substitute for alcohol use, people who engage in greater overall PA generally consume more alcohol on average than less-active peers. Acknowledging that both PA and alcohol use vary considerably from day-to-day, this study evaluated whether established associations reflect daily behavioral coupling within-person, are an artifact of procedures that aggregate behavior over time, or both. Methods: A life span sample of 150 adults (aged 19-89 years) completed three 21-day measurement bursts of a daily diary study. At the end of each day, they reported on their PA and alcohol consumption. Data were analyzed in a negative binomial multilevel regression. Results: As expected, both behaviors exhibited limited between-person variation. After controlling for age, gender, and seasonal and social calendar influences, daily deviations in PA were significantly associated with daily total alcohol use. Once the within-person process linking PA and alcohol use was controlled, usual PA and total alcohol use were not associated. Conclusions: The established between-person association linking PA and alcohol use reflects the aggregation of a daily process that unfolds within-people over time. Further work is needed to identify mediators of this daily association and to evaluate causality, as well as to investigate these relations in high-risk samples. (PsycINFO Database Record © 2014 APA, all rights reserved).

Concepts: Psychology, Aggregate, Behavior, Human behavior, Control, Wine, All rights reserved, Life span

40

Our society is increasingly relying on the digitized, aggregated opinions of others to make decisions. We therefore designed and analyzed a large-scale randomized experiment on a social news aggregation Web site to investigate whether knowledge of such aggregates distorts decision-making. Prior ratings created significant bias in individual rating behavior, and positive and negative social influences created asymmetric herding effects. Whereas negative social influence inspired users to correct manipulated ratings, positive social influence increased the likelihood of positive ratings by 32% and created accumulating positive herding that increased final ratings by 25% on average. This positive herding was topic-dependent and affected by whether individuals were viewing the opinions of friends or enemies. A mixture of changing opinion and greater turnout under both manipulations together with a natural tendency to up-vote on the site combined to create the herding effects. Such findings will help interpret collective judgment accurately and avoid social influence bias in collective intelligence in the future.

Concepts: Critical thinking, Future, Sociology, Aggregate, Mixture, Individual, Social influence, Opinion

39

Tactoids are nuclei of an orientationally ordered nematic phase that emerge upon cooling the isotropic phase. In addition to providing a natural setting for exploring chromonics under confinement, we show that tactoids can also serve as optical probes to delineate the role of temperature and concentration in the aggregation behavior of chromonics. For high concentrations, we observe the commonly reported elongated bipolar tactoids. As the concentration is lowered, breaking of achiral symmetry in the director configuration is observed with a predominance of twisted bipolar tactoids. On further reduction of concentration, a remarkable transformation of the director configuration occurs, wherein it conforms to a unique splay-minimizing configuration. Based on a simple model, we arrive at an interesting result that lower concentrations have longer aggregates at the same reduced temperature. Hence, the splay deformation that scales linearly with the aggregate length becomes prohibitive for lower concentrations and is relieved via twist and bend deformations in this unique configuration. Raman scattering measurements of the order parameters independently verify the trend in aggregate lengths and provide a physical picture of the nematic-biphasic transition.

Concepts: Fundamental physics concepts, Electrochemistry, Scattering, Aggregate, Aggregate data, Raman scattering, Liquid crystal, Phase diagram

37

The aggregation of amyloid-Aβ (Aβ) on lipid bilayers has been implicated as a mechanism by which Aβ exerts its toxicity in Alzheimer’s disease (AD). Lipid bilayer thinning has been observed during both oxidative stress and protein aggregation in AD, but whether these pathological modifications of the bilayer correlate with Aβ misfolding is unclear. Here, we studied peptide-lipid interactions in synthetic bilayers of the short-chain lipid dilauroyl phosphatidylcholine (DLPC) as a simplified model for diseased bilayers to determine their impact on Aβ aggregate, protofibril, and fibril formation. Aβ aggregation and fibril formation in membranes composed of dioleoyl phosphatidylcholine (DOPC) or 1- palmitoyl-2-oleoyl phosphatidylcholine (POPC) mimicking normal bilayers served as controls. Differences in aggregate formation and stability were monitored by a combination of thioflavin-T fluorescence, circular dichroism, AFM, TEM, and NMR. Despite the ability of all three lipid bilayers to catalyze aggregation, DLPC accelerates aggregation at much lower concentrations uniquely ablates the fibrillation of Aβ at low μM concentrations. DLPC stabilized globular, membrane-associated oligomers which could disrupt the bilayer integrity. DLPC bilayers also remodeled preformed amyloid fibrils into a pseudo-unfolded, molten globule state which resembled on-pathway, protofibrillar aggregates. While the stabilized, membrane-associated oligomers were found to be nontoxic, the remodeled species displayed toxicity similar to that of conventionally prepared aggregates. These results provide mechanistic insights into the roles that pathologically thin bilayers may play in Aβ aggregation on neuronal bilayers and pathological lipid oxidation may contribute to Aβ misfolding.

Concepts: Protein, Redox, Electrochemistry, Aggregate, Aggregate data, Lipid, Toxicity, Lipid bilayer

28

The time-evolutions of nanoparticle hydrodynamic radius and aggregate fractal dimension during the aggregation of fullerene (C(60)) nanoparticles (FNPs) were measured via simultaneous multiangle static and dynamic light scattering. The FNP aggregation behavior was determined as a function of monovalent (NaCl) and divalent (CaCl(2)) electrolyte concentration, and the impact of addition of dissolved natural organic matter (humic acid) to the solution was also investigated. In the absence of humic acid, the fractal dimension decreased over time with monovalent and divalent salts, suggesting that aggregates become slightly more open and less compact as they grow. Although the aggregates become slightly more open, the magnitude of the fractal dimension suggests intermediate aggregation between the diffusion- and reaction-limited regimes. We observed different aggregation behavior with monovalent and divalent salts upon the addition of humic acid to the solution. For NaCl-induced aggregation, the introduction of humic acid significantly suppressed the aggregation rate of FNPs at NaCl concentrations lower than 150mM. In this case, the aggregation was intermediate or reaction-limited even at NaCl concentrations as high as 500mM, giving rise to aggregates with a fractal dimension of 2.0. For CaCl(2)-induced aggregation, the introduction of humic acid enhanced the aggregation of FNPs at CaCl(2) concentrations greater than about 5mM due to calcium complexation and bridging effects. Humic acid also had an impact on the FNP aggregate structure in the presence of CaCl(2), resulting in a fractal dimension of 1.6 for the diffusion-limited aggregation regime. Our results with CaCl(2) indicate that in the presence of humic acid, FNP aggregates have a more open and loose structure than in the absence of humic acid. The aggregation results presented in this paper have important implications for the transport, chemical reactivity, and toxicity of engineered nanoparticles in aquatic environments.

Concepts: Chemistry, Soil, Aggregate, Aggregate data, Light scattering, Humus, Natural organic matter, Fractal

27

Abstract In this study, the effect of ZnO nanoparticles and ZnCl2 on growth, reproduction and accumulation of zinc in Daphnia magna was determined in a 21 day chronic toxicity test. A variety of techniques were used to distinguish the free zinc ion, dissolved, nanoparticle and aggregated zinc fraction in the daphnia test medium. The results showed similar chronic effects on growth, reproduction and accumulation for the ZnO nanoparticles (EC10, 20, 50 reproduction: 0.030, 0.049, 0.112 mg Zn/l) and the ZnCl2 (EC10, 20, 50 reproduction: 0.014, 0.027, 0.082 mg Zn/l). A large fraction of the nanoparticles rapidly dissolved after introduction in the exposure medium. Aggregation of nanoparticles was also observed but within 48 hours of exposure most of these ZnO aggregates were dissolved. Based on the combined dissolution kinetics and toxicity results it can be concluded that the toxicological effects of ZnO nanoparticles at the chronic level can be largely attributed to the dissolved fraction rather than the nanoparticles or initially formed aggregates.

Concepts: Ultraviolet, Aggregate, Toxicology, Zinc, Zinc oxide, Brass, Dr. Dre, Zinc chloride

26

The 5-phosphoinositide phosphatase Sac3, whose loss-of-function mutations are linked to neurodegenerative disorders, forms a stable cytosolic complex with the scaffolding protein ArPIKfyve. The ArPIKfyve-Sac3 heterodimer interacts with the phosphoinositide 5-kinase PIKfyve in a ubiquitous ternary complex that couples PtdIns(3,5)P(2) synthesis with turnover at endosomal membranes, thereby regulating the housekeeping endocytic transport in eukaryotes. Neuron-specific associations of the ArPIKfyve-Sac3 heterodimer, which may shed light on neuropathological mechanisms triggered by Sac3 dysfunction, are unknown. Here we conducted mass spectrometry analysis for brain-derived interactors of ArPIKfyve-Sac3 and unraveled the α-synuclein-interacting protein Synphilin-1 (Sph1) as a new component of the ArPIKfyve-Sac3 complex. Sph1, a predominantly neuronal protein that facilitates aggregation of α-synuclein, is a major component of Lewy body inclusions in neurodegenerative α-synucleinopathies. Modulations in ArPIKfyve/Sac3 protein levels by RNA silencing or overexpression in several mammalian cell lines, including human neuronal SH-SY5Y or primary mouse cortical neurons, revealed that the ArPIKfyve-Sac3 complex specifically altered aggregation properties of Sph1-GFP. This effect required an active Sac3 phosphatase and proceeded through mechanisms that involved increased Sph1-GFP partitioning into the cytosol and removal of Sph1-GFP aggregates by basal autophagy but not by the proteasomal system. If uncoupled from ArPIKfyve elevation, overexpressed Sac3 readily aggregated, markedly enhancing the aggregation potential of Sph1-GFP. These data identify a novel role of the ArPIKfyve-Sac3 complex in the mechanisms controlling aggregate formation of Sph1 and suggest that Sac3 protein deficiency or overproduction may facilitate aggregation of aggregation-prone proteins, thereby precipitating the onset of multiple neuronal disorders.

Concepts: Cell nucleus, Cell, Mutation, Cell membrane, Ribosome, Cerebral cortex, Aggregate, Aggregate data