Whiter, brighter, and more stable cellulose paper coated with antibacterial carboxymethyl starch stabilized ZnO nanoparticles

Small, carboxymethyl-starch-stabilised zinc oxide nanoparticles with a defined shape, size and morphology were prepared in situ in water at relatively low reaction temperatures using soluble carboxymethyl starch (CMS) as a combined crystallising, stabilising and solubilising agent and triethanolamine as the reducing agent. Aqueous colloidal solutions of these CMS-stabilised ZnO nanoparticles were used to deposit a coating of ZnO nanoparticles on cellulose paper by a wet-chemistry, polyelectrolyte, layer-by-layer approach using water as the only solvent. Such cellulose paper samples, coated with these CMS-stabilised ZnO nanoparticles, show higher brightness and whiteness than that of blank reference paper and are more stable to UV-radiation than the paper reference as well as demonstrating good antibacterial activity against MRSA and A. baumannii

Antifungal synergy of theaflavin and epicatechin combinations against Candida albicans

New antifungal agents are required to compensate for the increase in resistance to standard antifungal agents of Candida albicans, which is an important opportunistic fungal pathogen that causes minor infections in many individuals but very serious infections in those who are immune-compromised. In this study, combinations of theaflavin and epicatechin are investigated as potential antifungal agents and also to establish whether antifungal synergy exists between these two readily accessible and cost-effective polyphenols isolated from black and green tea. The results of disc diffusion assays showed stronger antibacterial activity of theaflavin:epicatechin combinations against C. albicans NCTC 3255 and NCTC 3179, than that of theaflavin alone. Minimum inhibitory concentrations (MICs) of 1,024 μg/ml with theaflavin and 128-256 μg/ml with theaflavin:epicatechin combinations were found. The fractional inhibitory concentration indexes were calculated, and the synergy between theaflavin and epicatechin against both isolates of C. albicans was confirmed. Theaflavin:epicatechin combinations show real potential for future use as a treatment for infections caused by C. albicans

Synergistic antibacterial effects of theaflavin in combination with ampicillin against hospital isolates of Stenotrophomonas Maltophilia

Stenotrophomonas maltophilia is an important opportunistic nosocomial pathogen that shows intrinsic resistance to many antibiotics. This often limits treatment options and can cause lengthy hospital stays. Combination treatments are often used to combat resistance and using natural compounds such as polyphenols could give increased treatment options and even the reuse of antibiotics to which high levels of resistance have been observed. A checkerboard assay was used to determine if any synergy exists between ampicillin and the polyphenol theaflavin against 9 clinical isolates and one control isolate (NCTC 13014) of S. maltophilia. It was discovered that significant synergy (P 0.05) does exist between theaflavin and ampicillin, reducing the mean MIC of ampicillin from 12.5-22.9 µg/mL, in liquid culture, to 3.125-6.25 µg/mL. The FIC index was calculated to be 0.22-0.35 confirming synergy. From these results, significant potential for medical applications can be seen and further investigation is recommended

In Vitro Antibacterial Activity of Curcumin-Polymyxin B Combinations against Multidrug-Resistant Bacteria Associated with Traumatic Wound Infections

Bacterial infections resulting from nonsurgical traumatic wounds can be life threatening, especially those caused by multidrug-resistant (MDR) bacteria with limited therapeutic options. The antimicrobial activity of polymyxin B (1) and curcumin (2) alone and in combination was determined versus MDR bacterial isolates associated with traumatic wound infections. Cytotoxicity assays for 1 and 2 were undertaken in keratinocyte cell lines. Minimum inhibitory concentrations of 1 were significantly reduced in the presence of 2 (3- to 10-fold reduction), with synergy observed. Time− kill assays showed the combinations produced bactericidal activity. Cytotoxicity assays indicate the toxicity of 2 was reduced in the presence of 1

A structural basis for prion strain diversity

Recent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML prion strains revealed a similar, parallel in-register intermolecular β-sheet (PIRIBS) amyloid architecture. Rungs of the fibrils are composed of individual prion protein (PrP) monomers that fold to create distinct N-terminal and C-terminal lobes. However, disparity in the hamster/mouse PrP sequence precludes understanding of how divergent prion strains emerge from an identical PrP substrate. In this study, we determined the near-atomic resolution cryo-EM structure of infectious, ex vivo mouse prion fibrils from the ME7 prion strain and compared this with the RML fibril structure. This structural comparison of two biologically distinct mouse-adapted prion strains suggests defined folding subdomains of PrP rungs and the way in which they are interrelated, providing a structural definition of intra-species prion strain-specific conformations

Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle

Nuclear reprogramming requires the removal of epigenetic modifications imposed on the chromatin during cellular differentiation and division. The mammalian oocyte can reverse these alterations to a state of totipotency, allowing the production of viable cloned offspring from somatic cell nuclei. To determine whether nuclear reprogramming is complete in cloned animals, we assessed the telomerase activity and telomere length status in cloned embryos, fetuses, and newborn offspring derived from somatic cell nuclear transfer. In this report, we show that telomerase activity was significantly (P < 0.05) diminished in bovine fibroblast donor cells compared with embryonic stem-like cells, and surprisingly was 16-fold higher in fetal fibroblasts compared with adult fibroblasts (P < 0.05). Cell passaging and culture periods under serum starvation conditions significantly decreased telomerase activity by approximately 30–50% compared with nontreated early passage cells (P < 0.05). Telomere shortening was observed during in vitro culture of bovine fetal fibroblasts and in very late passages of embryonic stem-like cells. Reprogramming of telomerase activity was apparent by the blastocyst stage of postcloning embryonic development, and telomere lengths were longer (15–23 kb) in cloned fetuses and offspring than the relatively short mean terminal restriction fragment lengths (14–18 kb) observed in adult donor cells. Overall, telomere lengths of cloned fetuses and newborn calves (≈20 kb) were not significantly different from those of age-matched control animals (P > 0.05). These results demonstrate that cloned embryos inherit genomic modifications acquired during the donor nuclei's in vivo and in vitro period but are subsequently reversed during development of the cloned animal

Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES–DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention

Humoral and Cell-Mediated Immunity to Pandemic H1N1 Influenza in a Canadian Cohort One Year Post-Pandemic: Implications for Vaccination

We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity

Depauperate Avifauna in Plantations Compared to Forests and Exurban Areas

Native forests are shrinking worldwide, causing a loss of biological diversity. Our ability to prioritize forest conservation actions is hampered by a lack of information about the relative impacts of different types of forest loss on biodiversity. In particular, we lack rigorous comparisons of the effects of clearing forests for tree plantations and for human settlements, two leading causes of deforestation worldwide. We compared avian diversity in forests, plantations and exurban areas on the Cumberland Plateau, USA, an area of global importance for biodiversity. By combining field surveys with digital habitat databases, and then analyzing diversity at multiple scales, we found that plantations had lower diversity and fewer conservation priority species than did other habitats. Exurban areas had higher diversity than did native forests, but native forests outscored exurban areas for some measures of conservation priority. Overall therefore, pine plantations had impoverished avian communities relative to both native forests and to exurban areas. Thus, reports on the status of forests give misleading signals about biological diversity when they include plantations in their estimates of forest cover but exclude forested areas in which humans live. Likewise, forest conservation programs should downgrade incentives for plantations and should include settled areas within their purview

No Excuses Charter Schools: A Meta-Analysis of the Experimental Evidence on Student Achievement

While charter schools differ widely in philosophy and pedagogical views, the United States’s most famous urban charter schools typically use the No Excuses approach. Enrolling mainly poor and minority students, these schools feature high academic standards, strict disciplinary codes, extended instructional time, and targeted supports for low-performing students. The strenuous and regimented style is controversial amongst some scholars, but others contend that the No Excuses approach is needed to rapidly close the achievement gap. We conduct the first meta-analysis of the achievement impacts of No Excuses charter schools. Focusing on experimental studies, we find that No Excuses charter schools significantly improve math scores and reading scores. We estimate gains of 0.25 and 0.16 standard deviations on math and literacy achievement, respectively, as the effect of attending a No Excuses charter school for one year. Though the effect is large and meaningful, we offer some caveats to this finding and discuss policy implications for the United States as well as other countries