A coil-globule transition of a semiflexible polymer driven by the addition of spherical particles

The phase behaviour of a single large semiflexible polymer immersed in a suspension of spherical particles is studied. All interactions are simple excluded volume interactions and the diameter of the spherical particles is an order of magnitude larger than the diameter of the polymer. The spherical particles induce a quite long ranged depletion attraction between the segments of the polymer and this induces a continuous coil-globule transition in the polymer. This behaviour gives an indication of the condensing effect of macromolecular crowding on DNA.Comment: 12 pages, 4 figure

Attention mechanisms in the CHREST cognitive architecture

In this paper, we describe the attention mechanisms in CHREST, a computational architecture of human visual expertise. CHREST organises information acquired by direct experience from the world in the form of chunks. These chunks are searched for, and verified, by a unique set of heuristics, comprising the attention mechanism. We explain how the attention mechanism combines bottom-up and top-down heuristics from internal and external sources of information. We describe some experimental evidence demonstrating the correspondence of CHREST’s perceptual mechanisms with those of human subjects. Finally, we discuss how visual attention can play an important role in actions carried out by human experts in domains such as chess

Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine

A biosustainable production route for 3-hydroxypropionic acid (3HP), an important platform chemical, would allow 3HP to be produced without using fossil fuels. We are interested in investigating a potential biochemical route to 3HP from pyruvate through b -alanine and, in this paper, we develop and solve a mathematical model for the reaction kinetics of the metabolites involved in this pathway. We consider two limiting cases, one where the levels of pyruvate are never replenished, the other where the levels of pyruvate are continuously replenished and thus kept constant. We exploit the natural separation of both the time scales and the metabolite concentrations to make significant asymptotic progress in understanding the system without resorting to computationally expensive parameter sweeps. Using our asymptotic results, we are able to predict the most important reactions to maximize the production of 3HP in this system while reducing the maximum amount of the toxic intermediate compound malonic semialdehyde present at any one time, and thus we are able to recommend which enzymes experimentalists should focus on manipulating

Detailed Investigation of the Role of Common and Low-Frequency WFS1 Variants in Type 2 Diabetes Risk

OBJECTIVE: Wolfram syndrome 1 (WFS1) single nucleotide polymorphisms (SNPs) are associated with risk of type 2 diabetes. In this study we aimed to refine this association and investigate the role of low-frequency WFS1 variants in type 2 diabetes risk. RESEARCH DESIGN AND METHODS: For fine-mapping, we sequenced WFS1 exons, splice junctions, and conserved noncoding sequences in samples from 24 type 2 diabetic case and 68 control subjects, selected tagging SNPs, and genotyped these in 959 U.K. type 2 diabetic case and 1,386 control subjects. The same genomic regions were sequenced in samples from 1,235 type 2 diabetic case and 1,668 control subjects to compare the frequency of rarer variants between case and control subjects. RESULTS: Of 31 tagging SNPs, the strongest associated was the previously untested 3' untranslated region rs1046320 (P = 0.008); odds ratio 0.84 and P = 6.59 x 10(-7) on further replication in 3,753 case and 4,198 control subjects. High correlation between rs1046320 and the original strongest SNP (rs10010131) (r2 = 0.92) meant that we could not differentiate between their effects in our samples. There was no difference in the cumulative frequency of 82 rare (minor allele frequency [MAF] 100,000) or studies in ethnically diverse populations. Low frequency variants in WFS1 are unlikely to have a large impact on type 2 diabetes risk in white U.K. populations, highlighting the complexities of undertaking association studies with low-frequency variants identified by resequencing

Rapid population decline in migratory shorebirds relying on Yellow Sea tidal mudflats as stopover sites

Migratory animals are threatened by human-induced global change. However, little is known about how stopover habitat, essential for refuelling during migration, affects the population dynamics of migratory species. Using 20 years of continent-wide citizen science data, we assess population trends of ten shorebird taxa that refuel on Yellow Sea tidal mudflats, a threatened ecosystem that has shrunk by >65% in recent decades. Seven of the taxa declined at rates of up to 8% per year. Taxa with the greatest reliance on the Yellow Sea as a stopover site showed the greatest declines, whereas those that stop primarily in other regions had slowly declining or stable populations. Decline rate was unaffected by shared evolutionary history among taxa and was not predicted by migration distance, breeding range size, non-breeding location, generation time or body size. These results suggest that changes in stopover habitat can severely limit migratory populations

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation

Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed “macromolecular crowding”. Here, we studied a model peptide that can fold to a stable monomeric β-hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric β-hairpin conformation was stabilized with respect to the unfolded state. Stabilization free energy was linear with cosolute concentration, and grew with molecular volume, as would also be predicted by crowding models. After initiating the aggregation process with a pH jump, fibrillation in the presence and absence of cosolutes was followed by ThT fluorescence, transmission electron microscopy, and CD spectroscopy. Polyols (glycerol and sorbitol) increased the lag time for fibril formation and elevated the amount of aggregated peptide at equilibrium, in a cosolute size and concentration dependent manner. However, fibrillation rates remained almost unaffected by a wide range of molecular weights of soluble polyethylene glycols. Our results highlight the importance of other forces beyond the excluded volume interactions responsible for crowding that may contribute to the cosolute effects acting on amyloid formation

Proteomic Shifts in Embryonic Stem Cells with Gene Dose Modifications Suggest the Presence of Balancer Proteins in Protein Regulatory Networks

Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of “balancer” proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the “elasticity” of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions

UV and optical light transmission properties in deep ice at the South Pole

Both absorption and scattering of light at wavelengths 410 to 610 nanometers were measured in the South Pole ice at depths 0.8 to 1 kilometer with the laser calibration system of the Antarctic Muon And Neutrino Detector Array (AMANDA). At the shortest wavelengths the absorption lengths exceeded 200 meters—an order of magnitude longer than has been reported for laboratory ice. The absorption shows a strong wavelength dependence while the scattering length is found to be independent of the wavelength, consistent with the hypothesis of a residual density of air bubbles in the ice. The observed linear decrease of the inverse scattering length with depth is compatible with an earlier measurement by the AMANDA collaboration (at ∼515 nanometers)

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues