Voltammetry of adsorbed monolayers: computer simulation and experiment

Facile and accurate determination of both kinetic and thermodynamic electrochemical parameters from simple cyclic voltammograms of adsorbed species has been achieved using a new computer based theoretical model. This removes, for the most part, a major deficiency in cyclic voltammetric analysis. This model incorporates an integrated approach to simulation in cyclic voltammetry involving a combination of Marcus electron transfer theory and a simplex fitting algorithm. The model uses a modem electron transfer theory in a unique way and is demonstrated to be an important and useful diagnostic tool for the electrochemist. With this model, the effect of the electrode material on the electrochemical response of adsorbed osmium complexes has been investigated and it has been found that the non-adiabatic rate of heterogeneous electron transfer does not depend simply on the density o f states within the electrode. In contrast, it is found that the non-adiabatic rate of heterogeneous electron transfer depends on the density of states modulated by the square of the coupling. Studies on the effect o f bond conjugation within bridging ligands in adsorbed monolayers using the electron transfer model have been carried out. Surprisingly, the presence of bond conjugation gives a lower rate constant. Analogous experiments were carried out on complexes in solution. The model has been comprehensively tested using both theoretical and experimental data and has proven to be highly sensitive to the heterogeneous electron transfer rate constant, k°, and to a lesser extent, the reorganisation energy, X. This electron transfer model will enable future studies of adsorbed monolayers where distributions of formal potentials and / or distributions of heterogeneous electron transfer rate constants exist

Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) ( ). CDVA exhibited no change between baseline and exit visits ( and , resp.). Measures of visual function that did exhibit statistically significant improvements ( for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition

Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro.

OBJECTIVE: Staphylococcus aureus is the most frequent causative organism of infective endocarditis (IE) and is characterized by thrombus formation on a cardiac valve that can embolize to a distant site. Previously, we showed that S. aureus clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) can stimulate rapid platelet aggregation. METHODS AND RESULTS: In this study we investigate their relative roles in mediating aggregate formation under physiological shear conditions. Platelets failed to interact with immobilized wild-type S. aureus (Newman) at shear rates \u3c500\u3es(-1) but rapidly formed an aggregate at shear rates \u3e800 s(-1). Inactivation of the ClfA gene eliminated aggregate formation at any shear rate. Using surrogate hosts that do not interact with platelets bacteria overexpressing ClfA supported rapid aggregate formation under high shear with a similar profile to Newman whereas bacteria overexpressing FnBPA did not. Fibrinogen binding to ClfA was found to be essential for aggregate formation although fibrinogen-coated surfaces only allowed single-platelets to adhere under all shear conditions. Blockade of the platelet immunoglobulin receptor Fc gammaRIIa inhibited aggregate formation. CONCLUSIONS: Thus, fibrinogen and IgG binding to ClfA is essential for aggregate formation under arterial shear conditions and may explain why S. aureus is the major cause of IE

Elucidating the role of Staphylococcus epidermidis serine-aspartate repeat protein G in platelet activation.

BACKGROUND: Staphylococcus epidermidis is a commensal of the human skin that has been implicated in infective endocarditis and infections involving implanted medical devices. S. epidermidis induces platelet aggregation by an unknown mechanism. The fibrinogen-binding protein serine-aspartate repeat protein G (SdrG) is present in 67-91% of clinical strains. OBJECTIVES: To determine whether SdrG plays a role in platelet activation, and if so to investigate the role of fibrinogen in this mechanism. METHODS: SdrG was expressed in a surrogate host, Lactococcus lactis, in order to investigate its role in the absence of other staphylococcal components. Platelet adhesion and platelet aggregation assays were employed. RESULTS: L. lactis expressing SdrG stimulated platelet aggregation (lag time: 2.9 +/- 0.5 min), whereas the L. lactis control did not. L. lactis SdrG-induced aggregation was inhibited by alpha(IIb)beta3 antagonists and aspirin. Aggregation was dependent on both fibrinogen and IgG, and the platelet IgG receptor FcgammaRIIa. Preincubation of the bacteria with Bbeta-chain fibrinopeptide inhibited aggregation (delaying the lag time six-fold), suggesting that fibrinogen acts as a bridging molecule. Platelets adhered to L. lactis SdrG in the absence of fibrinogen. Adhesion was inhibited by alpha(IIb)beta3 antagonists, suggesting that this direct interaction involves alpha(IIb)beta3. Investigation using purified fragments of SdrG revealed a direct interaction with the B-domains. Adhesion to the A-domain involved both a fibrinogen and an IgG bridge. CONCLUSION: SdrG alone is sufficient to support platelet adhesion and aggregation through both direct and indirect mechanisms

Impact of computer experience on the viability and repeatability of the Moorfields Motion Displacement Test (MMDT) in a developing and underserved African setting.

Background: The current study was designed to explore the effect of computer experience on the viability and testretest repeatability of the Moorfields Motion Displacement Test (MMDT), a novel computer-driven glaucoma screening device, in an African community setting. Methods: 164 healthy subjects were recruited from a semi-rural Mozambican environment, and stratified according to computer experience (computer naïve: n=85, computer familiar: n=79). A suprathreshold screening test algorithm was employed, and the global probability of true damage (GPTD), testing time (TT) and false positive (FP) response rate were recorded. The visual field test was conducted twice on the same eye, and results compared to determine intra-sessional repeatability. Results: No inter-group differences in GPTD or TT (p\u3e0.05) were observed between computer subgroups, although FP response rate was significantly higher among computer naïve subjects (p=0.00 for both tests). No inter-sessional differences were observed for GPTD, TT and FP (p\u3e0.05 for all) for either subgroup. A statistically significant positive correlation was found between repeat GPTD, TT and FP measures for all subgroups (

Sequence diversity in the A domain of Staphylococcus aureus fibronectin-binding protein A

<p>Abstract</p> <p>Background</p> <p>Fibronectin-binding protein A (FnBPA) mediates adhesion of <it>Staphylococcus aureus </it>to fibronectin, fibrinogen and elastin. We previously reported that <it>S. aureus </it>strain P1 encodes an FnBPA protein where the fibrinogen/elastin-binding domain (A domain) is substantially divergent in amino acid sequence from the archetypal FnBPA of <it>S. aureus </it>NCTC8325, and that these variations created differences in antigenicity. In this study strains from multilocus sequence types (MLST) that spanned the genetic diversity of <it>S.aureus </it>were examined to determine the extent of FnBPA A domain variation within the <it>S. aureus </it>population and its effect on ligand binding and immuno-crossreactivity.</p> <p>Results</p> <p>Seven different isotype forms (I – VII) of the FnBPA A domain were identified which were between 66 to 76% identical in amino acid sequence in any pair-wise alignment. The <it>fnbA </it>allelic variants in strains of different multilocus sequence type were identified by DNA hybridization using probes specific for sequences encoding the highly divergent N3 sub-domain of different isotypes. Several isotypes were not restricted to specific clones or clonal complexes but were more widely distributed. It is highly likely that certain <it>fnbA </it>genes have been transferred horizontally. Residues lining the putative ligand-binding trench were conserved, which is consistent with the ability of each A domain isotype to bind immobilized fibrinogen and elastin by the dock-latch-lock mechanism. Variant amino acid residues were mapped on a three-dimensional model of the FnBPA A domain and were predicted to be surface-exposed. Polyclonal antibodies raised against the recombinant isotype I A domain bound that protein with a 4 – 7 fold higher apparent affinity compared to the A domains of isotypes II – VII, while some monoclonal antibodies generated against the isotype I A domain showed reduced or no binding to the other isotypes.</p> <p>Conclusion</p> <p>The FnBPA A domain occurs in at least 7 different isotypes which differ antigenically and exhibit limited immuno-crossreactivity, yet retain their ligand-binding functions. Antigenic variation of the FnBPA A domain may aid <it>S. aureus </it>to evade the host's immune responses. These findings have implications for the development of vaccines or immunotherapeutics that target FnBPA.</p

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats.

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours

Age-related macular degeneration patients' awareness of nutritional factors

Age-related macular degeneration (AMD) is the leading cause of visual impairment in older adults in the United Kingdom. This study sought to characterise AMD patients who seek the services of the Macular Society, and determine the level and source of their dietary knowledge. A questionnaire was designed, validated, and administered to 158 participants. The questions covered demographic data and knowledge of nutrition and supplementation. The mean age of participants was 79 years; 61% of them were female, and 27% were registered visually impaired. Only 55% of the participants thought diet was important for eye health, 63% felt that they had not received enough information about AMD. The participants reported that their information mainly came from non-professional support groups. Most participants identified healthy food, but could not say why, and were not able to identify carotenoid rich foods. The results of the study will inform design of education and dissemination methods regarding dietary information