ZipA Binds to FtsZ with High Affinity and Enhances the Stability of FtsZ Protofilaments

A bacterial membrane protein ZipA that tethers FtsZ to the membrane is known to promote FtsZ assembly. In this study, the binding of ZipA to FtsZ was monitored using fluorescence spectroscopy. ZipA was found to bind to FtsZ with high affinities at three different (6.0, 6.8 and 8.0) pHs, albeit the binding affinity decreased with increasing pH. Further, thick bundles of FtsZ protofilaments were observed in the presence of ZipA under the pH conditions used in this study indicating that ZipA can promote FtsZ assembly and stabilize FtsZ polymers under unfavorable conditions. Bis-ANS, a hydrophobic probe, decreased the interaction of FtsZ and ZipA indicating that the interaction between FtsZ and ZipA is hydrophobic in nature. ZipA prevented the dilution induced disassembly of FtsZ polymers suggesting that it stabilizes FtsZ protofilaments. Fluorescein isothiocyanate-labeled ZipA was found to be uniformly distributed along the length of the FtsZ protofilaments indicating that ZipA stabilizes FtsZ protofilaments by cross-linking them

An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles

BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano), and showed further increase in dimension (75-95 etam) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver. CONCLUSIONS: The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney

Revealing and capitalising on young children’s mathematical potential

With ongoing concerns about environments that push teachers toward increasingly structured assessments, thus reducing opportunities to observe young learners’ mathematical capabilities, the publication of this special issue on formative assessment is especially significant and timely. The articles illustrate how we cannot rely solely on standardized achievement tests to determine learners’ actual mathematical competencies, nor to determine their learning potential, nor to fully identify possible areas in need of further development. In this commentary I first consider some of the important issues examined in the articles and then turn to Ginsburg’s general principles listed in his opening article. These principles are particularly helpful in not only guiding early assessment but also in providing quality mathematics education to young children. Building on ideas featured in this issue, I offer suggestions for how we might reveal and capitalise on young children’s mathematical talents. Examples from analogical and mathematical reasoning, spatial and numerical relations, numerical problem solving and posing, and combinatorial reasoning are presented

FTIR spectral analysis of bituminous binders: reproducibility and impact of ageing temperature

This RILEM round robin study with nine participating laboratories investigated bitumen ageing, its effect on chemical properties and its reproducibility. The impact of temperature used for short-term (RTFOT) binder ageing on the combined short- and long-term (PAV) aged samples was investigated; thereby the effect of reduced mixing temperature such as those relevant for warm mix asphalt technologies on long term ageing was examined. Four 70/100 penetration graded bituminous binders from different sources were selected. In addition to the standard RTFOT temperature of 163 °C, two additional temperatures, 143 and 123 °C were used. The Fourier transform infrared spectroscopy (FTIR) analysis was carried out using an integration method which considers the area below the absorbance spectrum around a band maximum using baseline and tangential approaches. A statistical investigation into the reproducibility of FTIR spectra analysis based on the accumulated data was done. To assess the reproducibility, the coefficient of variation (CV) was taken as a benchmark parameter. Carbonyl and sulfoxide indices were calculated using different baseline correction methods and tangential and baseline integration, respectively. It was shown that the tangential method was not influenced by the applied baseline correction. However, in all considered cases, the tangential method led to significantly worse reproducibility (CVs ranging from 20 to 120%) compared to the baseline method. The sulfoxide indices calculated by both methods were not affected by the baseline correction method used. Impacts of changes in the short-term ageing temperature on short- or long-term aged samples could not be found whereas differences between different binder sources could be detected. RTFOT temperature and therefore mix production temperature had a stronger impact on the formation of sulfoxide structures than for carbonyl structures. The findings from this study show the most reproducible of all considered methods when more than one laboratory is providing FTIR data.Max Kade Foundatio

The academic environment: the students’ perspective

Dental education is regarded as a complex, demanding and often stressful pedagogical procedure. Undergraduates, while enrolled in programmes of 4-6 years duration, are required to attain a unique and diverse collection of competences. Despite the major differences in educational systems, philosophies, methods and resources available worldwide, dental students' views regarding their education appear to be relatively convergent. This paper summarizes dental students' standpoint of their studies, showcases their experiences in different educational settings and discusses the characteristics of a positive academic environment. It is a consensus opinion that the 'students' perspective' should be taken into consideration in all discussions and decisions regarding dental education. Moreover, it is suggested that the set of recommendations proposed can improve students' quality of life and well-being, enhance their total educational experience and positively influence their future careers as oral health physicians. The 'ideal' academic environment may be defined as one that best prepares students for their future professional life and contributes towards their personal development, psychosomatic and social well-being. A number of diverse factors significantly influence the way students perceive and experience their education. These range from 'class size', 'leisure time' and 'assessment procedures' to 'relations with peers and faculty', 'ethical climate' and 'extra-curricular opportunities'. Research has revealed that stress symptoms, including psychological and psychosomatic manifestations, are prevalent among dental students. Apparently some stressors are inherent in dental studies. Nevertheless, suggested strategies and preventive interventions can reduce or eliminate many sources of stress and appropriate support services should be readily available. A key point for the Working Group has been the discrimination between 'teaching' and 'learning'. It is suggested that the educational content should be made available to students through a variety of methods, because individual learning styles and preferences vary considerably. Regardless of the educational philosophy adopted, students should be placed at the centre of the process. Moreover, it is critical that they are encouraged to take responsibility for their own learning. Other improvements suggested include increased formative assessment and self-assessment opportunities, reflective portfolios, collaborative learning, familiarization with and increased implementation of information and communication technology applications, early clinical exposure, greater emphasis on qualitative criteria in clinical education, community placements, and other extracurricular experiences such as international exchanges and awareness of minority and global health issues. The establishment of a global network in dental education is firmly supported but to be effective it will need active student representation and involvement