Search

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na1-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator- like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrateinduced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na1 and succinate. We also observe separable effects of Na1 and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na1 binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site-associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family. [ABSTRACT FROM AUTHOR]

Ostensibly hydrophilic alginates are known to foul hydrophobic membranes, under various conditions. Here, controlled experiments have been conducted at high and low pH on the fouling of a polypropylene membrane by alginate and the results suggest that the observed fouling is due to an intrinsic property of the alginate. Thus quantum chemical calculations on the M and G monomers of alginate reveal that M adopts an equilibrium geometry that is hydrophilic on one face and hydrophobic on the other, i.e. is potentially amphiphilic. Molecular dynamics simulations on short alginate chains of different sequences interacting with a modelled polypropylene surface, show that this characteristic is carried over to the polymer and results in hydrophobic patches along the chain that facilitate attractive interactions with the polypropylene surface. This concept is buttressed by an analysis of the binding characteristics of a previously reported X-ray structure of the mannuronan C-5 epimerase AlgE4 enzyme. [ABSTRACT FROM AUTHOR]

Whilst the involvement of poly-G sequences in the formation of metal-mediated alginate gels has been previously studied in some detail, investigations into the role of poly-M and poly-GM sequences has been relatively neglected. In this regard, the binding of sodium and calcium ions to poly-M and poly-GM decamers, and their influence on chain aggregation, has been modelled by conducting a series of molecular dynamics simulations. This work complements a previous analogous study carried out for the poly-G decamer, whereby up to three strands are systematically introduced into each simulation. As in the previous study, this method allows intrinsic binding modes and interchain structural motifs to be revealed, that are consistent with those observed in available AFM images of consolidated 3-D networks. It is apparent from these studies that different sequences have different structural implications for metal-mediated chain association. [ABSTRACT FROM AUTHOR]

Abstract: The binding of sodium and calcium ions to single and multiple poly-G decamer strands has been modelled by conducting a series of molecular dynamics simulations. Implications for metal mediated inter-strand interactions and gel assembly have been explored by systematically introducing up to three strands into each of these simulations. A particular emphasis has been placed on revealing intrinsic binding modes by an unbiased initial positioning of the metal ions. The results have revealed binding modes that provide a rationale for the observed gelling of alginate by calcium rather than sodium ions. A number of junction zones involving calcium ions have been identified that result in chain aggregation. This includes a distinctive perpendicular motif that appears to be ubiquitous in previously reported AFM images of open 3-D alginate networks. The coordination geometries of the metal ions have been characterised and the metal-mediated junctions between associated strands are described in detail. [Copyright &y& Elsevier]

Abstract: The formation of aggregates of sodium alginate and bovine serum albumin (BSA) (as representative biopolymers) with humic acid were detected by Liquid Chromatography (LC) UV254 response in the biopolymer region for mixture solutions. BSA interaction with humic acid showed that aggregation occurred both in the presence and absence of calcium, suggesting that multivalent ions did not play a part in the aggregation process. Similar analyses of the alginate interaction with humic acid also showed a positive interaction, but only in the presence of calcium ions. The fouling characteristics for the BSA–humic acid mixture appeared to be significantly greater than the fouling characteristics of the individual solutions, while for the sodium alginate–humic acid mixture, the fouling rate was similar to that of the sodium alginate alone. The effectiveness of hydraulic backwashing, 10–15% reversibility, was observed for the BSA-humic acid mixture, while the % reversibility was 20–40% for the sodium alginate–humic acid mixture. Increased humic acid and DOC rejection were observed for both BSA–humic acid and sodium alginate–humic acid solutions compared to the individual solutions, indicating that the biopolymer filter cakes were able to retain humic acids. When compared with BSA–humic acid mixture solution, greater removal of humic acid was observed for alginate–humic mixture, suggesting that sodium alginate may have a greater capacity for associations with humic acid when in the presence of calcium than BSA. Complementary molecular dynamics simulations were designed to provide insights into the specific mechanisms of interaction between BSA and humic acid, as well as between alginate and humic acid. For the BSA–humic acid system; electrostatic, hydrophobic and hydrogen bonding were the dominant types of interactions predicted, whilst divalent ion-mediated bonding was not identified in the simulations, which supported the LC-results. Similarly for the alginate–humic acid system, the interactions predicted were divalent ion-mediated interactions only and this was also supported the LC results. This work suggests that LC-UV254 might be used to identify aggregated biopolymers, and that combined with current characterisation techniques, be used to better explain performance variations between water sources. [Copyright &y& Elsevier]

Abstract: This paper investigates the role of microtopographical features on the cytomorphology, alignment, proliferation and gene expression of tenocytes. We made use of simple microfabrication approaches to create surfaces patterned with topographical features suitable for in vitro studies of tenocytes. These surfaces were composed of glass substrates patterned with polymeric ridges spaced from 50 to 250μm apart. Our studies demonstrate that the microgrooves differentially impact tenocyte shape, alignment and matrix organization along the direction of grooves. Groove widths significantly influenced cellular alignment, with 50μm grooved patterns affecting alignment most substantially. Polarized light microscopy demonstrated that mature collagen fibers were denser and more oriented within 50μm patterns. None of the patterns had a significant effect on the expression of genes linked to proliferation or extracellular matrix synthesis, although time in culture profoundly influenced both gene groups. COMP mRNA expression was moderately increased in tenocytes seeded onto 250μm grooves, but there was no overall beneficial phenotypic effect of aligned growth. The results of this study indicate that microtopography affects cell density and alignment of tenocytes and leads to the deposition of an aligned collagen matrix, but does not significantly impact matrix gene expression or cell phenotype. These outcomes provide insights into the biology of tendon regeneration, thus providing guidance in the design of clinical procedures for tendon repair. [Copyright &y& Elsevier]

Summary: Warm-up and stretching are widely used as techniques in preparation for intense physical activity, yet there is little information available to compare their effectiveness in relation to athletic performance. Fourteen elite Under-19 year old rugby league footballers undertook each of four preparation protocols (no preparation, stretching only, warm-up only, warm-up and stretching) in four successive testing sessions. Protocols were randomly allocated to players in a counterbalanced design so that each type of preparation occurred equally on each day of testing. During each session, athletes performed three solo sprint trials at maximum speed. Sprints were of 40-m distance and were electronically timed with wind speed and direction recorded. Preparation involving warm-up resulted in significantly faster sprint times compared to preparations having no warm-up, with a diminishing effect over the three trials. On the first trial, warm-up resulted in a mean advantage of 0.97m over 40m. Stretching resulted in a mean disadvantage of 0.18m on the first trial, and no significant effect overall despite significant wind assistance. Warm-up was effective at improving immediate sprint performance, whereas an equivalent duration of lower limb stretching had no effect. [Copyright &y& Elsevier]

Article Title and Bibliographic Information The success of stainless steel crowns placed with the Hall technique: a retrospective study. Ludwig KH, Fontana M, Vinson LA, Platt JA, Dean JA. J Am Dent Assoc 2014;145(12):1248–53. Reviewers Nicola P. T. Innes, PhD, BDS (Hons), BSc, BMSc (Hons), Matthew Stewart, BDS Purpose/Question Are stainless steel crowns placed using the Hall Technique as clinically and radiographically successful as crowns placed using the traditional method, when used to manage caries lesions in primary molars in children in a private practice setting? Source of Funding Information not available Type of Study/Design Retrospective cohort study Level of Evidence Level 2: Limited-quality, patient-oriented evidence Strength of Recommendation Level Not applicable [ABSTRACT FROM AUTHOR]

• Practical considerations for using ionized gas as a barometer. • Modeling of non-linear effects due to ion recombination. • Modeling of non-linear effects due to ionizing radiation emission pattern. • Experimentally verified ionized gas barometer model. A model has been developed and experimentally verified to determine the feasibility of ionizing a gas to measure barometric pressure. Alpha particles emitted from an americium 241 source ionize the gas. The number of ions created depends directly on the number of alpha particle-gas molecule interactions which is proportional to gas pressure. An electric field applied to the ionized gas causes current proportional to the ion count and therefore gas pressure. Several nonlinear effects have been identified and modeled including gas chamber geometry, alpha particle source emission pattern and ion recombination. The lack of any moving components or dependence on material strain leads to resistance to shock and strain. With suitable low power amplification electronics, overall power level of a few μW can be achieved. The cm scale of the sensing element would be the driving factor in the size of a final device. [ABSTRACT FROM AUTHOR]

Large vestibular aqueduct syndrome (LVAS) is a congenital inner ear malformation that commonly results in progressive sensorineural hearing loss (SNHL) and cochlear implantation (CI). Though LVAS accounts for approximately 15% of pediatric SNHL, little is known regarding the rate and severity of SNHL in these patients. We sought to characterize the timing of SNHL progression to CI in patients with LVAS. We performed a retrospective chart review at our institution from 2000 to 2018 using ICD-10 "large vestibular aqueduct syndrome," and through identifying patients with CI who had LVAS. Demographic, surgical, and audiometric data were collected. Theoretical CI candidacy was approximated using a pure tone average (PTA) HL threshold of 70 dB. Of 103 patients, 96 had bilateral LVAS, and 7 had unilateral LVAS. Forty-one patients had bilateral implants, 52 had unilateral implants, and 10 were not implanted. The mean age at first implant was 8.62 years old [95%CI = 6.75,10.49], the mean age at second implant was 12.24 years old [95%CI = 8.33,16.15], and the mean time between implants was 4.37 years [95%CI = 3.02,5.73]. LVAS patients reached HL threshold of 70 dB at a mean age of 5.16 years old (SD = 3.04) for the "worse ear" and 9.08 years old (SD = 4.96) for the "better ear." LVAS patients are a heterogenous population of patients, in which some may undergo progression of HL and some may not. Further, there may be a discrepancy in the timing between patients' theoretical CI candidacy and when they undergo CI. In order to optimize timing of CI, individual monitoring and close observation of LVAS patients is recommended. [ABSTRACT FROM AUTHOR]

Abstract Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds (EDCs) are frequently detected in drinking water sources. This raises concerns about the formation of potentially more toxic transformation products (TPs) after drinking water disinfection. This study applied a combination of computational and experimental methods to investigate the biological activity of eight EDCs and PPCPs commonly detected in source waters (acetaminophen, bisphenol A, carbamazepine, estrone, 17α-ethinylestradiol, gemfibrozil, naproxen and triclosan) before and after disinfection. Using a Stepped Forced Molecular Dynamics (SFMD) method, we detected 911 unique TPs, 36% of which have been previously reported in the scientific literature. We calculated the likelihood that TPs would cause damage to biomolecules or DNA relative to the parent compound based on lipophilicity and the occurrence of structural alerts, and applied two Quantitative Structure-Activity Relationship (QSAR) tools to predict toxicity via receptor-mediated effects. In parallel, batch experiments were performed with three disinfectants, chlorine, chlorine dioxide and chloramine. After solid-phase extraction, the resulting TP mixtures were analyzed by chemical analysis and a battery of eleven in vitro bioassays covering a variety of endpoints. The laboratory results were in good agreement with the predictions. Overall, the combination of computational and experimental chemistry and toxicity methods used in this study suggest that disinfection of the studied EDCs and PPCPs will produce a large number of TPs, which are unlikely to increase specific toxicity (e.g., endocrine activity), but may result in increased reactive and non-specific toxicity. Graphical abstract Unlabelled Image Highlights • Endocrine disrupting compounds (EDCs) frequently detected in drinking water sources • Raises concern that disinfection of drinking water could produce more potent EDCs • This study applied a combination of computational and experimental methods. • Chlorination decreased specific, but increased reactive & non-specific toxicity. • Toxicity less than that produced from reaction of chlorine with organic matter [ABSTRACT FROM AUTHOR]

The objective of this research was to establish effects of selected process parameters (component ratio, pH, shear) on the properties of alginate (Alg)/beta lactoglobulin (βlg) mixtures. Effects were assessed by measuring apparent viscosity, particle size, ζ-potential, hydrophobicity and conformational changes (FTIR). Intrinsic viscosity and critical concentrations were also investigated. Intrinsic viscosity of individual Alg and βlg solutions increased with pH. Shearing of Alg/βlg mixtures resulted in greater apparent viscosity at pH 3 which declined proportional to increase in pH. Particle size and surface hydrophobicity were higher at pH 3 and directly related to Alg concentration. Shear induced changes were observed in the secondary structure of βlg in the βlg/Alg mixtures associated with β-sheet conformations shifting from 1635.64 to 1633.71/cm and occurred only at pH 5. Under certain conditions, application of shear could manipulate and create different structures from these two biopolymers. [ABSTRACT FROM AUTHOR]

The impact of secondary effluent wastewater from the Eastern Treatment Plant (ETP), Melbourne, Australia, before and after ion exchange (IX) treatment and polyaluminium chlorohydrate (PACl) coagulation, on hydrophobic polypropylene (PP) and hydrophilic polyvinylidene fluoride (PVDF) membrane fouling was studied. Laboratory fouling tests were operated over 3–5 days with regular, intermittent backwash. During the filtration with PP membranes, organic rejection data indicated that humic adsorption on hydrophobic PP membrane occurred during the first 24 h of filtration and contributed to fouling for both raw wastewater and pre-treated wastewaters. However, after the first 24 h of filtration the contribution of humic substances to fouling diminished and biopolymers that contribute to cake layer development became more prominent in their contribution to the fouling rate. For PVDF membranes, the per cent removal of humic substances from both raw wastewater and pre-treated wastewaters was very small as indicated by no change in UV 254 from the feed to the permeate over the filtration period, even during the early stages of filtration. This suggested that the hydrophobic PP membrane adsorbed humic substances while the hydrophilic PVDF membrane did not. The highest mass of biopolymer removal by each PVDF membrane was from ETP water followed by PACl and IX treated water respectively. This was possibly due to differences in the backwashing efficiency linked to the filter cake contributed by biopolymers. Hydraulic backwashing was more effective during the later stages of filtration for the ETP water compared to IX and PACl treated waters, indicating that the filter cake contributed by ETP biopolymers was more extensively removed by hydraulic backwashing. It was proposed that humic substances may act to stabilise biopolymers in solution and that removing humics substances by coagulation or IX results in greater adhesive forces between the biopolymers and membrane/filter cake. Extended laboratory filtration is required to understand fouling of low pressure membranes as it relates to commercial applications, as the initial rate of fouling for new membranes can include pore constriction mechanisms from humic substances which diminish in significance as filtration continues. Filtration for >24 h was required before the HIFI values became constant. [ABSTRACT FROM AUTHOR]

Abstract: The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA) and fluorescence spectroscopy (Method A), and UV254, organic carbon and organic nitrogen detectors (Method B), was undertaken on wastewater before and after magnetic IX treatment. Results showed partial removal of the biopolymer fraction at high IX doses. With increasing concentration of IX, evidence for nitrogen-containing compounds such as proteins and amino acids disappeared from the LC-OND chromatogram, complementary to the fluorescence response. A greater fluorescence response of tryptophan-like proteins (278 nm/343 nm) for low IX concentrations was consistent with aggregation of tryptophan-like compounds into larger aggregates, either by self-aggregation or with polysaccharides. Recycling of IX resin through multiple adsorption steps without regeneration maintained the high level of humics removal but there was no continued removal of biopolymer. Subsequent membrane filtration of the IX treated waters resulted in complex fouling trends. Filtration tests with either polypropylene (PP) or polyvinylidene fluoride (PVDF) membranes showed higher rates of initial fouling following treatment with high IX doses (10 mL/L) compared to filtration of untreated water, while treatment with lower IX doses resulted in decreased fouling rates relative to the untreated water. However, at longer filtration times the rate of fouling of IX treated waters was lower than untreated water and the relative fouling rates corresponded to the amount of biopolymer material in the feed. It was proposed that the mode of fouling changed from pore constriction during the initial filtration period to filter cake build up at longer filtration times. The organic composition strongly influenced the rate of fouling during the initial filtration period due to competitive adsorption processes, while at longer filtration times the rate of fouling appeared to depend upon the amount of biopolymer material in the feed water. [Copyright &y& Elsevier]

Abstract: Extensive organic characterisation of a wastewater using liquid chromatography with a photodiode array and fluorescence spectroscopy (Method A), and UV254 and organic carbon detector (Method B) was undertaken, as well as with fluorescence excitation emission spectroscopy (EEM). Characterisation was performed on the wastewater before and after ion exchange (IX) treatment and polyaluminium chlorohydrate (PACl) coagulation, and following microfiltration of the wastewater and pre-treated wastewaters. Characterisation by EEM was unable to detect biopolymers within the humic rich wastewaters and was not subsequently used to characterise the MF permeates. IX treatment preferentially removed low molecular weight (MW) organic acids and neutrals, and moderate amounts of biopolymers in contrast to a previous report of no biopolymer removal with IX. PACl preferentially removed moderate MW humic and fulvic acids, and large amounts of biopolymers. PACl showed a great preference for removal of proteins from the biopolymer component in comparison to IX. An increase in the fluorescence response of tryptophan-like compounds in the biopolymer fraction following IX treatment suggests that low MW neutrals may influence the structure and/or inhibit aggregation of organic compounds. Fouling rates for IX and PACl treated wastewaters had high initial fouling rates that reduced to lower fouling rates with time, while the untreated Eastern Treatment Plant (ETP) wastewater displayed a consistent, high rate of fouling. The results for the IX and PACl treated wastewaters were consistent with the long-term fouling rate being determined by cake filtration while both pore constriction and cake filtration contributed to the higher initial fouling rates. Higher rejection of biopolymers was observed for PACl and IX waters compared to the untreated ETP water, suggesting increased adhesion of biopolymers to the membrane or cake layer may lead to the higher rejection. [Copyright &y& Elsevier]

Abstract: Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization procedures and affect osseointegration. The goals of this study were to develop a murine model of osseointegration in order to determine whether removing surface contaminants enhances osseointegration. To develop the murine model, titanium alloy implants were implanted into a unicortical pilot hole in the mid-diaphysis of the femur and osseointegration was measured over a five week time course. Histology, backscatter scanning electron microscopy and X-ray energy dispersive spectroscopy showed areas of bone in intimate physical contact with the implant, confirming osseointegration. Histomorphometric quantification of bone-to-implant contact and peri-implant bone and biomechanical pullout quantification of ultimate force, stiffness and work to failure increased significantly over time, also demonstrating successful osseointegration. We also found that a rigorous cleaning procedure significantly enhances bone-to-implant contact and biomechanical pullout measures by two-fold compared with implants that were autoclaved, as recommended by the manufacturer. The most likely interpretation of these results is that surface contaminants inhibit osseointegration. The results of this study justify the need for the development of better detection and removal techniques for contaminants on orthopedic implants and other medical devices. [Copyright &y& Elsevier]

• Miura Ori cellular structure investigated as a potential protective material. • Taguchi methodology enabled efficient investigation of mulitple parameters. • Linear impacts at 3 velocities performed to simulate American football collisions. • Novel approach to defining performance via single outcome measure. • Final structure more efficient than helmet-derived foam across 3 impact velocities. American football has a comparatively high rate of sports-related concussions, despite mitigating strategies including the use of protective helmets. The traditional energy absorbing component, elastomeric foam pads, have limited scope for leveraging any further protection. Alternative structures and materials that exhibit novel deformation mechanics have been proposed as a route to increased energy absorption capacity. This study investigated a metamaterial based on the Miura Ori folding pattern. Eighty-one potential structural variations were conceptualised and evaluated via the Taguchi method. Twenty-seven geometries were then additively manufactured using commercially available thermoplastic polyurethane, before being impacted at multiple velocities. Experimental data were then extrapolated to predict the impact behaviour across all 81 variants. An optimised geometry was then proposed, which reduced linear accelerations across the test conditions and performed favourably when compared to current, elastomeric foam solutions. This work provides a promising foundation for future investigation. [ABSTRACT FROM AUTHOR]