An accelerated buoyancy adhesion assay combined with 3-D morphometric analysis for assessing osteoblast adhesion on microgrooved substrata.

An accelerated negative buoyancy method has been developed to assess cell adhesion strength. This method has been used in conjunction with 3-D morphometric analysis to understand the effects of surface topology on cell response. Aligned micro-grooved surface topographies (with a range of groove depths) were produced on stainless steel 316L substrates by laser ablation. An investigation was carried out on the effect of the micro-grooved surface topography on cell adhesion strength, cell and nucleus volumes, cell phenotypic expression and attachment patterns. Increased hydrophobicity and anisotropic wettability was observed on surfaces with deeper grooves. A reduction was noted in cell volume, projected areas and adhesion sites for deeper grooves, linked to lower cell proliferation and differentiation rates and also to reduced adhesion strength. The results suggest that the centrifugation assay combined with three-dimensional cell morphometric analysis has considerable potential for obtaining improved understanding of the cell/substrate interface.Financial support for this work has been provided by the EPSRC (grant GR/R95364/01) and by the ERC (grant No. 240446). The authors are grateful to Dr. Tim Nunney, of Thermo-Fisher Scientific, for carrying out the XPS measurements.This is the final version of the article. It first appeared from Elsevier via https://doi.org/ /10.1016/j.jmbbm.2015.12.03

Counterfeit drugs and the online pharmaceutical trade, a threat to public safety

Counterfeit pharmaceuticals are a serious and ever-growing threat to public safety. Monitoring the trade is difficult, resulting in the precise scale of the problem being unknown, however evidence shows that it is not just lifestyle drugs that are targeted nowadays. Adverse health problems, including fatalities, have resulted from consumers self-medicating with counterfeit products. Without efforts to enhance the public's knowledge, the problem will continue to persist. The internet is facilitating the trade by providing counterfeiters with a large consumer base and limited risks. The dark net within it allows for anonymous transactions between manufacturer, distributer and consumer. While some online pharmacies are legitimate, there are a growing number of those that are unverified which sell dangerous counterfeit products. Both the packaging and medication are becoming increasingly sophisticated, making it difficult for consumers and law enforcement to identify them without chemical analysis. Counterfeit batches have also been detected in established legal trade routes whereby they are able to, if undetected, end up in high street pharmacies and hospitals. Multiple organisations have set up worldwide operations to dismantle the trade however this is a complex and evolving problem that without significant changes to legislation may never be fully

Effect of Differential Rotation on the Magnetic Braking of Low-mass and Solar-like Stars: A Proof-of-concept Study

This is the final version. Available on open access from IOP Publishing via the DOI in this recordOn the main sequence, low-mass and solar-like stars are observed to spin down over time, and magnetized stellar winds are thought to be predominantly responsible for this significant angular momentum loss. Previous studies have demonstrated that the wind torque can be predicted via formulations dependent on stellar properties, such as magnetic field strength and geometry, stellar radius and mass, wind mass-loss rate, and stellar rotation rate. Although these stars are observed to experience surface differential rotation, torque formulations so far have assumed solid-body rotation. Surface differential rotation is expected to affect the rotation of the wind and thus the angular momentum loss. To investigate how differential rotation affects the torque, we use the PLUTO code to perform 2.5D magnetohydrodynamic, axisymmetric simulations of stellar winds, using a colatitude-dependent surface differential rotation profile that is solar-like (i.e., rotation is slower at the poles than the equator). We demonstrate that the torque is determined by the average rotation rate in the wind so that the net torque is less than that predicted by assuming solid-body rotation at the equatorial rate. The magnitude of the effect is essentially proportional to the magnitude of the surface differential rotation, for example, resulting in a torque for the Sun that is 1/420% smaller than predicted by the solid-body assumption. We derive and fit a semianalytic formulation that predicts the torque as a function of the equatorial spin rate, magnitude of differential rotation, and wind magnetization (depending on the dipolar magnetic field strength and mass-loss rate, combined).European Union Horizon 2020European Research Council (ERC

Using ESTs to improve the accuracy of de novo gene prediction

BACKGROUND: ESTs are a tremendous resource for determining the exon-intron structures of genes, but even extensive EST sequencing tends to leave many exons and genes untouched. Gene prediction systems based exclusively on EST alignments miss these exons and genes, leading to poor sensitivity. De novo gene prediction systems, which ignore ESTs in favor of genomic sequence, can predict such "untouched" exons, but they are less accurate when predicting exons to which ESTs align. TWINSCAN is the most accurate de novo gene finder available for nematodes and N-SCAN is the most accurate for mammals, as measured by exact CDS gene prediction and exact exon prediction. RESULTS: TWINSCAN_EST is a new system that successfully combines EST alignments with TWINSCAN. On the whole C. elegans genome TWINSCAN_EST shows 14% improvement in sensitivity and 13% in specificity in predicting exact gene structures compared to TWINSCAN without EST alignments. Not only are the structures revealed by EST alignments predicted correctly, but these also constrain the predictions without alignments, improving their accuracy. For the human genome, we used the same approach with N-SCAN, creating N-SCAN_EST. On the whole genome, N-SCAN_EST produced a 6% improvement in sensitivity and 1% in specificity of exact gene structure predictions compared to N-SCAN. CONCLUSION: TWINSCAN_EST and N-SCAN_EST are more accurate than TWINSCAN and N-SCAN, while retaining their ability to discover novel genes to which no ESTs align. Thus, we recommend using the EST versions of these programs to annotate any genome for which EST information is available. TWINSCAN_EST and N-SCAN_EST are part of the TWINSCAN open source software package

Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

Gravito-electromagnetic analogies

We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.Comment: 60 pages, 2 figures. Improved version (compared to v2) with some re-write, notation improvements and a new figure that match the published version; expanded compared to the published version to include Secs. 2.3 and

Cross-Modal Object Recognition Is Viewpoint-Independent

BACKGROUND: Previous research suggests that visual and haptic object recognition are viewpoint-dependent both within- and cross-modally. However, this conclusion may not be generally valid as it was reached using objects oriented along their extended y-axis, resulting in differential surface processing in vision and touch. In the present study, we removed this differential by presenting objects along the z-axis, thus making all object surfaces more equally available to vision and touch. METHODOLOGY/PRINCIPAL FINDINGS: Participants studied previously unfamiliar objects, in groups of four, using either vision or touch. Subsequently, they performed a four-alternative forced-choice object identification task with the studied objects presented in both unrotated and rotated (180 degrees about the x-, y-, and z-axes) orientations. Rotation impaired within-modal recognition accuracy in both vision and touch, but not cross-modal recognition accuracy. Within-modally, visual recognition accuracy was reduced by rotation about the x- and y-axes more than the z-axis, whilst haptic recognition was equally affected by rotation about all three axes. Cross-modal (but not within-modal) accuracy correlated with spatial (but not object) imagery scores. CONCLUSIONS/SIGNIFICANCE: The viewpoint-independence of cross-modal object identification points to its mediation by a high-level abstract representation. The correlation between spatial imagery scores and cross-modal performance suggest that construction of this high-level representation is linked to the ability to perform spatial transformations. Within-modal viewpoint-dependence appears to have a different basis in vision than in touch, possibly due to surface occlusion being important in vision but not touch

Towards responsible use of cognitive-enhancing drugs by the healthy

In this article, we propose actions that will help society accept the benefits of enhancement, given appropriate research and evolved regulation. Prescription drugs are regulated as such not for their enhancing properties but primarily for considerations of safety and potential abuse. Still, cognitive enhancement has much to offer individuals and society, and a proper societal response will involve making enhancements available while managing their risks

Use of non-steroidal anti-inflammatory drugs and risk of breast cancer: The Spanish Multi-Case-control (MCC) study

Background: The relationship between non-steroidal anti-inflammatory drug (NSAID) consumption and breast cancer has been repeatedly studied, although the results remain controversial. Most case-control studies reported that NSAID consumption protected against breast cancer, while most cohort studies did not find this effect. Most studies have dealt with NSAIDs as a whole group or with specific drugs, such aspirin, ibuprofen, or others, but not with NSAID subgroups according to the Anatomical Therapeutic Chemical Classification System; moreover, scarce attention has been paid to their effect on different tumor categories (i.e.: ductal/non-ductal, stage at diagnosis or presence of hormonal receptors). Methods: In this case-control study, we report the NSAID – breast cancer relationship in 1736 breast cancer cases and 1895 healthy controls; results are reported stratifying by the women’s characteristics (i.e.: menopausal status or body mass index category) and by tumor characteristics. Results: In our study, NSAID use was associated with a 24 % reduction in breast cancer risk (Odds ratio [OR] = 0.76; 95 % Confidence Interval [CI]: 0.64–0.89), and similar results were found for acetic acid derivatives, propionic acid derivatives and COXIBs, but not for aspirin. Similar results were found in postmenopausal and premenopausal women. NSAID consumption also protected against hormone + or HER2+ cancers, but not against triple negative breast cancers. The COX-2 selectivity showed an inverse association with breast cancer (i.e. OR < 1), except in advanced clinical stage and triple negative cancers. Conclusion: Most NSAIDs, but not aspirin, showed an inverse association against breast cancer; this effect seems to be restricted to hormone + or HER2+ cancers. Keywords: Breast cancer, Non-steroidal anti-inflammatory drug, Hormone receptor positive breast cancer, HER2 positive breast cancer, Triple negative breast cance