Protein-polymer nano-machines. Towards synthetic control of biological processes

The exploitation of nature's machinery at length scales below the dimensions of a cell is an exciting challenge for biologists, chemists and physicists, while advances in our understanding of these biological motifs are now providing an opportunity to develop real single molecule devices for technological applications. Single molecule studies are already well advanced and biological molecular motors are being used to guide the design of nano-scale machines. However, controlling the specific functions of these devices in biological systems under changing conditions is difficult. In this review we describe the principles underlying the development of a molecular motor with numerous potential applications in nanotechnology and the use of specific synthetic polymers as prototypic molecular switches for control of the motor function. The molecular motor is a derivative of a TypeI Restriction-Modification (R-M) enzyme and the synthetic polymer is drawn from the class of materials that exhibit a temperature-dependent phase transition. The potential exploitation of single molecules as functional devices has been heralded as the dawn of new era in biotechnology and medicine. It is not surprising, therefore, that the efforts of numerous multidisciplinary teams [1,2]. have been focused in attempts to develop these systems. as machines capable of functioning at the low sub-micron and nanometre length-scales [3]. However, one of the obstacles for the practical application of single molecule devices is the lack of functional control methods in biological media, under changing conditions. In this review we describe the conceptual basis for a molecular motor (a derivative of a TypeI Restriction-Modification enzyme) with numerous potential applications in nanotechnology and the use of specific synthetic polymers as prototypic molecular switches for controlling the motor function [4]

Treating and Preventing Influenza in Aged Care Facilities: A Cluster Randomised Controlled Trial

PMCID: PMC3474842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)

The (Mtb) pathogen encodes an -acetylglucosamine-6-phosphate deacetylase enzyme, NagA (Rv3332), that belongs to the amidohydrolase superfamily. NagA enzymes catalyze the deacetylation of -acetylglucosamine-6-phosphate (GlcNAc6P) to glucosamine-6-phosphate (GlcN6P). NagA is a potential anti-tubercular drug target because it represents the key enzymatic step in the generation of essential amino-sugar precursors required for cell wall biosynthesis and also influences recycling of cell wall peptidoglycan fragments. Here, we report the structural and functional characterization of NagA from (MSNagA) and (MMNagA), close relatives of Using a combination of X-ray crystallography, site-directed mutagenesis, and biochemical and biophysical assays, we show that these mycobacterial NagA enzymes are selective for GlcNAc6P. Site-directed mutagenesis studies revealed crucial roles of conserved residues in the active site that underpin stereo-selective recognition, binding, and catalysis of substrates. Moreover, we report the crystal structure of MSNagA in both ligand-free form and in complex with the GlcNAc6P substrate at 2.6 Å and 2.0 Å resolutions, respectively. The GlcNAc6P-complex structure disclosed the precise mode of GlcNAc6P binding and the structural framework of the active site, including two divalent metals located in the α/β binuclear site. Furthermore, we observed a cysteine residue located on a flexible loop region that occludes the active site. This cysteine is unique to mycobacteria and may represent a unique subsite for targeting mycobacterial NagA enzymes. Our results provide critical insights into the structural and mechanistic properties of mycobacterial NagA enzymes having an essential role in amino-sugar and nucleotide metabolism in mycobacteria

Small-scale Dynamo in Cool Stars: I. Changes in stratification and near-surface convection for main-sequence spectral types

Some of the small-scale solar magnetic flux can be attributed to a small-scale dynamo (SSD) operating in the near-surface convection. The SSD fields have consequences for solar granular convection, basal flux, as well as chromospheric heating. A similar SSD mechanism is expected to be active in the near-surface convection of other cool main-sequence stars, but this has never been investigated. We aim to investigate changes in stratification and convection due to inclusion of SSD fields for F3V, G2V, K0V and M0V spectral types in the near-surface convection. 3D magnetohydrodynamic (MHD) models of the four stellar boxes, covering the subsurface convection zone up to the lower photosphere in a small cartesian box, are studied using the \textit{MURaM} radiative-MHD simulation code. The SSD runs are compared against reference hydrodynamic runs. An SSD is found to efficiently produce magnetic field with energies ranging between 5\% to 80\% of the plasma kinetic energy at different depths. This ratio tends to be larger for larger $T_{\mathrm{eff}}$. The relative change in density and gas pressure stratification for the deeper convective layers due to SSD magnetic fields is negligible, except for the F-star. For the F-star, there is a substantial reduction in convective velocities due to Lorentz force feedback from magnetic fields, which, in turn, reduces the turbulent pressure. SSD in near-surface convection for cool main-sequence stars introduces small but significant changes in thermodynamic stratification (especially for the F-star) due to reduction in convective velocities.Comment: 10 pages, 7 figures, accepted for publication in A&

One Versus Two Handedness: Directional Preference in a Silent-Failure Scenario

This study focused on the direction drivers of a self-driving car will turn to avoid a crash at a T-intersection. We hypothesized that drivers would steer differently when they drive using both hands and when they use their dominant hand only. Specifically, we hypothesized that participants would favor the direction of their dominant hand (if they use their dominant hand only) and that there with be no directional preference if driving with both hands.. To test this hypothesis, we implemented a driving simulator study. We asked the participants to use either both their hands or only their dominant hand to avoid a crash. We are currently analyzing the data. Keywords: one-handed, two-handed, automated vehicle, silent takeover, directional preferenc

The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1

Crystal structures of a membrane protein transporter in three different conformational states provide insights into the transport mechanism

Impact of Porous Silica Nanosphere Architectures on the Catalytic Performance of Supported Sulphonic Acid Sites for Fructose Dehydration to 5‐Hydroxymethylfurfural

5‐hydroxymethylfurfural represents a key chemical in the drive towards a sustainable circular economy within the chemical industry. The final step in 5‐hydroxymethylfurfural production is the acid catalysed dehydration of fructose, for which supported organoacids are excellent potential catalyst candidates. Here we report a range of solid acid catalysis based on sulphonic acid grafted onto different porous silica nanosphere architectures, as confirmed by TEM, N2 porosimetry, XPS and ATR‐IR. All four catalysts display enhanced active site normalised activity and productivity, relative to alternative silica supported equivalent systems in the literature, with in‐pore diffusion of both substrate and product key to both performance and humin formation pathway. An increase in‐pore diffusion coefficient of 5‐hydroxymethylfurfural within wormlike and stellate structures results in optimal productivity. In contrast, poor diffusion within a raspberry‐like morphology decreases rates of 5‐hydroxymethylfurfural production and increases its consumption within humin formation

Thermoresponsive magnetic colloidal gels via surface-initiated polymerisation from functional microparticles

Novel magnetothermally responsive core-shell microparticles have been synthesized. The aqueous suspensions of these particles exhibit fast thermoreversible fluid-to-gel transitions and retain good magnetic properties. Rheological measurements demonstrated that the viscoelasticity of the prepared particle gels can be tuned, enabling these gels to have the mechanical properties that should facilitate their applications as 3D cell scaffolds for in vitro expansion of cells. Also, it was found that the responsive particles could be used in repeated heating-cooling cycles without marked changes in gel elasticity. Presto Blue viability assays of 3T3 fibroblasts and human mesenchymal sem cells cultured within the colloidal gel showed that the cells remained viable and proliferated, with significant increases in cell numbers over extended culture times. Confocal microscopy images of 3T3 cells cultured within the colloidal gel demonstrated that cells adhered, spread and retained their normal morphologies during proliferation.. Furthermore, magnetic separation allowed efficient recovery of cells after their expansion in vitro without need for enzyme-mediated release steps. Trypsin-free cell passages were performed allowing multiple growth, separation and reloading of cells within the colloidal gels. Overall, the results suggest this colloidal gel has potential as a 3D scaffold for in vitro expansion of a variety of cell types and for enzyme free cell harvesting

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

The Changing Face of Water: A Dynamic Reflection of Antibiotic Resistance Across Landscapes

Little is known about the role of surface water in the propagation of antibiotic resistance (AR), or the relationship between AR and water quality declines. While healthcare and agricultural sectors are considered the main contributors to AR dissemination, few studies have been conducted in their absence. Using linear models and Bayesian kriging, we evaluate AR among Escherichia coli water isolates collected bimonthly from the Chobe River in Northern Botswana (n = 1997, n = 414 water samples; July 2011–May 2012) in relation to water quality dynamics (E. coli, fecal coliform, and total suspended solids), land use, season, and AR in wildlife and humans within this system. No commercial agricultural or large medical facilities exist within this region. Here, we identify widespread AR in surface water, with land use and season significant predicators of AR levels. Mean AR was significantly higher in the wet season than the dry season (p = 0.003), and highest in the urban landscape (2.15, SD = 0.098) than the protected landscape (1.39, SD = 0.051). In-water E. coli concentrations were significantly positively associated with mean AR in the wet season (p &lt; 0.001) but not in the dry season (p = 0.110), with TSS negatively associated with mean AR across seasons (p = 0.016 and p = 0.029), identifying temporal and spatial relationships between water quality variables and AR. Importantly, when human, water, and wildlife isolates were examined, similar AR profiles were identified (p &lt; 0.001). Our results suggest that direct human inputs are sufficient for extensive dispersal of AR into the environment, with landscape features, season, and water quality variables influencing AR dynamics. Focused and expensive efforts to minimize pollution from agricultural sources, while important, may only provide incremental benefits to the management of AR across complex landscapes. Controlling direct human AR inputs into the environment remains a critical and pressing challenge