Modulation of Phosducin-Like Protein 3 (PhLP3) Levels Promotes Cytoskeletal Remodelling in a MAPK and RhoA-Dependent Manner

Background Phosducin-like protein 3 (PhLP3) forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in ?-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of ?-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems. Methodology/Principal Findings As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO) cell lines. We show that over-expression of PhLP3 promotes an imbalance of ? and ? tubulin subunits, microtubule disassembly and cell death. In contrast, ?-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state. Conclusions Our results support the hypothesis that PhLP3 is important for the maintenance of ?-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially relevant cell lines to evolve lines more suited to suspension or adherent cell growth

Diagnostic comparison of three groups of examiners using visual and laser fluorescence methods to detect occlusal caries in vitro

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: To evaluate the accuracy of the DIAGNOdent laser device (DD) for detecting occlusal fissure caries when used by three groups of examiners. Methods: Three final-year dental students (S), three General Dental Practitioners (G), and three Academic Clinicians (A) individually examined the non-cavitated occlusal surfaces of 25 extracted permanent molars using visual inspection (VI) then DD assessments. The presence of caries was confirmed following tooth sectioning. A cut-off limit of 30 was used for the DD to avoid over-treatment in a low caries-risk situation. Results: For VI, individual examiner sensitivity (caries correctly diagnosed) ranged from 53 to 86 per cent, and specificity (sound teeth correctly diagnosed) ranged from 76 to 95 per cent, with low Kappa agreements. Group S achieved the highest sensitivity (80 per cent) and Groups G and A achieved the highest specificities (88 per cent). For DD, individual examiner sensitivity ranged from 19 to 77 per cent, and specificity from 71 to 97 per cent, with generally moderate Kappa agreements. Group A achieved the highest (67 per cent) and Group G the lowest (44 per cent) sensitivities, and Group G achieved the highest specificity (94 per cent). Conclusions: There were similar widely varying results for the two diagnostic methods and for the three groups of examiners. However, the relatively high sensitivities found with VI and specificities found with DD should avoid over-treatment in low caries-risk populations.L Fung, R Smale, H Ngo and G Moun

The effect of precursor structure on porous carbons produced by iron-catalyzed graphitization of biomass

This paper reports a systematic study into the effect of different biomass-derived precursors on the structure and porosity of carbons prepared via catalytic graphitization. Glucose, starch and cellulose are combined with iron nitrate and heated under a nitrogen atmosphere to produce Fe3C nanoparticles, which catalyze the conversion of amorphous carbon to graphitic nanostructures. The choice of organic precursor provides a means of controlling the catalyst particle size, which has a direct effect on the porosity of the material. Cellulose and glucose produce mesoporous carbons, while starch produces a mixture of micro- and mesopores under the same conditions and proceeds via a much slower graphitization step, generating a mixture of graphitic nanostructures and turbostratic carbon. Porous carbons are critical to energy applications such as batteries and electrocatalytic processes. For these applications, a simple and sustainable route to those carbons is essential. Therefore, the ability to control the precise structure of a biomass-derived carbon simply through the choice of precursor will enable the production of a new generation of energy materials

Publisher Correction: Liquid phase blending of metal-organic frameworks

The original version of this Article contained an error in Figure 1b, where the blue ‘(ZIF-4-Zn)0.5 (ZIF-62)0.5 blend’ data curve was omitted from the enthalpy response plot. This has now been corrected in both the PDF and HTML versions of the Article

An extreme firm-specific news sentiment asymmetry based trading strategy

News sentiment has been empirically observed to have impact on financial market returns. In this study, we investigate firm-specific news from the Thomson Reuters News Analytics data from 2003 to 2014 and propose an optimal trading strategy based on a sentiment shock score and a sentiment trend score which measure extreme positive and negative sentiment levels for individual stocks. The intuition behind this approach is that the impact of events that generate extreme investor sentiment changes tends to have long and lasting effects to market movement and hence provides better prediction to market returns. We document that there exists an optimal signal region for both indicators. And we also show extreme positive sentiment provides better a signal than extreme negative sentiment, which presents an asymmetric market behavior in terms of news sentiment impact. The back test results show that extreme positive sentiment generates robust and superior trading signals in all market conditions, and its risk-adjusted returns significantly outperform the S&P 500 index over the same time period

Oral diagnosis and treatment planning: Part 6. Preventive and treatment planning for periodontal disease

A high level of sustained personal plaque control is fundamental for successful treatment outcomes in patients with active periodontal disease and, hence, oral hygiene instructions are the cornerstone of periodontal treatment planning. Other risk factors for periodontal disease also should be identified and modified where possible. Many restorative dental treatments in particular require the establishment of healthy periodontal tissues for their clinical success. Failure by patients to control dental plaque because of inappropriate designs and materials for restorations and prostheses will result in the long-term failure of the restorations and the loss of supporting tissues. Periodontal treatment planning considerations are also very relevant to endodontic, orthodontic and osseointegrated dental implant conditions and proposed therapies.E. Corbet and R. Smale

Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells

Objectives: To develop a recombinant human factor IX (rFIX) formulation equivalent to commercially available products in terms of cake appearance, residual moisture, proportion of soluble aggregates and activity maintenance for 3 months at 4–8 °C. Results: NaCl and low bulking agent/cryoprotectant mass ratio had a negative impact on cake quality upon lyophilisation for a wide range of formulations tested. Particular devised formulations maintained rFIX activity after lyophilization with a similar performance when compared with the rFIX formulated using the excipients reported for a commercially available FIX formulation (Benefix). rFIX remained active after 3 months when stored at 4 °C, though this was not the case with samples stored at 40 °C. Interestingly, particular formulations had an increase in residual moisture after 3 months storage, but not above a 3% threshold. All four formulations tested were equivalent to the Benefix formulation in terms of particle size distribution and cake appearance. Conclusions: Three specific formulations, consisting of surfactant polysorbate-80, sucrose or trehalose as cryoprotectant, mannitol or glycine as bulking agent, l-histidine as buffering agent, and NaCl added in the reconstitution liquid at 0.234% (w/v) were suitable for use with a CHO cell-derived recombinant FIX

Dietary behavior and knowledge of dental erosion among Chinese adults

<p>Abstract</p> <p>Objectives</p> <p>To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong.</p> <p>Methods</p> <p>Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion.</p> <p>Results</p> <p>A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries.</p> <p>Conclusion</p> <p>Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.</p

Absence of carious lesions at margins of glass-ionomer cement and amalgam restorations: An update of systematic review evidence

<p>Abstract</p> <p>Background</p> <p>This article aims to update the existing systematic review evidence elicited by Mickenautsch et al. up to 18 January 2008 (published in the European Journal of Paediatric Dentistry in 2009) and addressing the review question of whether, in the same dentition and same cavity class, glass-ionomer cement (GIC) restored cavities show less recurrent carious lesions on cavity margins than cavities restored with amalgam.</p> <p>Methods</p> <p>The systematic literature search was extended beyond the original search date and a further hand-search and reference check was done. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets extracted from the accepted trials.</p> <p>Results</p> <p>The database search (up to 10 August 2010) identified 1 new trial, in addition to the 9 included in the original systematic review, and 11 further trials were included after a hand-search and reference check. Of these 21 trials, 11 were excluded and 10 were accepted for data extraction and quality assessment. Thirteen dichotomous datasets of primary outcomes and 4 datasets with secondary outcomes were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall results of the computed datasets suggest that GIC has a higher caries-preventive effect than amalgam for restorations in permanent teeth. No difference was found for restorations in the primary dentition.</p> <p>Conclusion</p> <p>This outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection/performance bias is high. Thus, verification of the currently available results requires further high-quality randomised control trials.</p