Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

A cognitive-experiential approach to modelling web navigation

Flow experience, the degree to which a person feels involved in a particular activity, is an important influence on human–computer interaction. Building on Guo and Poole’s (2009) model of flow experience in Web navigation, and van Schaik and Ling's (in press) cognitive-experiential approach to modelling interaction experience, this research demonstrates the crucial role of the preconditions of flow experience in human–computer interaction. In an experiment, the preconditions of flow experience – but not flow experience proper – mediated the effects of artefact complexity, task complexity and intrinsic motivation (as a situation-specific trait) on both flow and task outcome. However, preconditions did not predict overall artefact evaluation. Within a staged model of flow experience, the broader implications of this work for human–computer interaction are explored.     

The right view from the wrong location: depth perception in stereoscopic multi-user virtual environments

Stereoscopic depth cues improve depth perception and increase immersion within virtual environments (VEs). However, improper display of these cues can distort perceived distances and directions. Consider a multi-user VE, where all users view identical stereoscopic images regardless of physical location. In this scenario, cues are typically customized for one "leader" equipped with a head-tracking device. This user stands at the center of projection (CoP) and all other users ("followers") view the scene from other locations and receive improper depth cues. This paper examines perceived depth distortion when viewing stereoscopic VEs from follower perspectives and the impact of these distortions on collaborative spatial judgments. Pairs of participants made collaborative depth judgments of virtual shapes viewed from the CoP or after displacement forward or backward. Forward and backward displacement caused perceived depth compression and expansion, respectively, with greater compression than expansion. Furthermore, distortion was less than predicted by a ray-intersection model of stereo geometry. Collaboration times were significantly longer when participants stood at different locations compared to the same location, and increased with greater perceived depth discrepancy between the two viewing locations. These findings advance our understanding of spatial distortions in multi-user VEs, and suggest a strategy for reducing distortion.     

Posterior representation with a multi‐modal likelihood using the gaussian sum filter for localization in a known map

A Gaussian sum filter (GSF) with component extended Kalman filters (EKF) is proposed as an approach to localizing an autonomous vehicle in an urban environment with limited GPS availability. The GSF uses vehicle‐relative vision‐based measurements of known map features coupled with inertial navigation solutions to accomplish localization in the absence of GPS. The vision‐based measurements have multimodal measurement likelihood functions that are well represented as weighted sums of Gaussian densities. The GSF is used because of its ability to represent the posterior distribution of the vehicle pose with better efficiency (fewer terms, less computational complexity) than a corresponding bootstrap particle filter with various numbers of particles because of the interaction with measurement hypothesis tests. The expectation‐maximization algorithm is used off line to determine the representational efficiency of the particle filter in terms of an effective number of Gaussian densities. In comparison, the GSF, which uses an iterative condensation procedure after each iteration of the filter to maintain real‐time capabilities, is shown through a series of in‐depth empirical studies to more accurately maintain a representation of the posterior distribution than the particle filter using 37 min of recorded data from Cornell University's autonomous vehicle driven in an urban environment, including a 32 min GPS blackout. © 2012 Wiley Periodicals, Inc.     

Scale-up and control of droplet production in coupled microfluidic flow-focusing geometries

A single microfluidic chip consisting of six microfluidic flow-focusing devices operating in parallel was developed to investigate the feasibility of scaling microfluidic droplet generation up to production rates of hundreds of milliliters per hour. The design utilizes a single inlet channel for both the dispersed aqueous phase and the continuous oil phase from which the fluids were distributed to all six flow-focusing devices. The exit tubing for each of the six flow-focusing devices is separate and individually plumbed to each device. Within each flow-focusing device, the droplet size was monodisperse, but some droplet size variations were observed across devices. We show that by modifying the flow resistance in the outlet channel of an individual flow-focusing device it is possible to control both the droplet size and frequency of droplet production. This can be achieved through the use of valves or, as is done in this study, by changing the length of the exit tubing plumbed to the outlet of the each device. Longer exit tubing and larger flow resistance is found to lead to larger droplets and higher production frequencies. The devices can thus be individually tuned to create a monodisperse emulsion or an emulsion with a specific drop size distribution.     

Multiple Na,K-ATPase Subunits Colocalize in the Brush Border of Mouse Choroid Plexus Epithelial Cells

(1) Background: The unusual accumulation of Na,K-ATPase complexes in the brush border membrane of choroid plexus epithelial cells have intrigued researchers for decades. However, the full range of the expressed Na,K-ATPase subunits and their relation to the microvillus cytoskeleton remains unknown. (2) Methods: RT-PCR analysis, co-immunoprecipitation, native PAGE, mass spectrometry, and differential centrifugation were combined with high-resolution immunofluorescence histochemistry, proximity ligase assays, and stimulated emission depletion (STED) microscopy on mouse choroid plexus cells or tissues in order to resolve these issues. (3) Results: The choroid plexus epithelium expresses Na,K-ATPase subunits α1, α2, β1, β2, β3, and phospholemman. The α1, α2, β1, and β2, subunits are all localized to the brush border membrane, where they appear to form a complex. The ATPase complexes may stabilize in the brush border membrane via anchoring to microvillar actin indirectly through ankyrin-3 or directly via other co-precipitated proteins. Aquaporin 1 (AQP1) may form part of the proposed multi-protein complexes in contrast to another membrane protein, the Na-K-2Cl cotransporter 1 (NKCC1). NKCC1 expression seems necessary for full brush border membrane accumulation of the Na,K-ATPase in the choroid plexus. (4) Conclusion: A multitude of Na,K-ATPase subunits form molecular complexes in the choroid plexus brush border, which may bind to the cytoskeleton by various alternative actin binding proteins.     

Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.     

Quantification of secondary structure prediction improvement using multiple alignments

The use of multiple sequence alignments for secondary structurepredictions is analysed. Seven different protein families, containingonly sequences of known structure, were considered to providea range of alignment and prediction conditions. Using alignmentsobtained by spatial superposition of main chain atoms in knowntertiary protein structures allowed a mean of 8% in secondarystructure prediction accuracy, when compared to those obtainedfrom the individual sequences. Substitution of these alignmentsby those determined directly from an automated sequence alignmentalgorithm showed variations in the prediction accuracy whichcorrelated with the quality of the multiple alignments and distanceof the primary sequence. Secondary structure predictions canbe reliably improved using alignments from an automatic alignmentprocedure with a mean increase of 6.87percnt;, giving an overallprediction accuracy of 68.5%, if there is a minimum of 25% sequenceidentity between all sequences in a family.