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As multidrug-resistant bacteria represent a concerning burden, experts insist on the need for a dramatic rethinking on antibiotic use and development in order to avoid a post-antibiotic era. New and rapidly developable strategies for antimicrobial substances, in particular substances highly potent against multidrug-resistant bacteria, are urgently required. Some of the treatment options currently available for multidrug-resistant bacteria are considerably limited by side effects and unfavorable pharmacokinetics. The glycopeptide vancomycin is considered an antibiotic of last resort. Its use is challenged by bacterial strains exhibiting various types of resistance. Therefore, in this study, highly active polycationic peptide-vancomycin conjugates with varying linker characteristics or the addition of PEG moieties were synthesized to optimize pharmacokinetics while retaining or even increasing antimicrobial activity in comparison to vancomycin. The antimicrobial activity of the novel conjugates was determined by microdilution assays on susceptible and vancomycin-resistant bacterial strains. VAN1 and VAN2, the most promising linker-modified derivatives, were further characterized in vivo with molecular imaging and biodistribution studies in rodents, showing that the linker moiety influences both antimicrobial activity and pharmacokinetics. Encouragingly, VAN2 was able to undercut the resistance breakpoint in microdilution assays on vanB and vanC vancomycin-resistant enterococci. Out of all PEGylated derivatives, VAN:PEG1 and VAN:PEG3 were able to overcome vanC resistance. Biodistribution studies of the novel derivatives revealed significant changes in pharmacokinetics when compared with vancomycin. In conclusion, linker modification of vancomycin-polycationic peptide conjugates represents a promising strategy for the modulation of pharmacokinetic behavior while providing potent antimicrobial activity.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

Superabsorbent polymers (SAPs) can be added to a concrete mixture to provide internal curing and reduce the risk for early-age shrinkage cracking. Hence, they can help to increase the overall durability of concrete structures. The type, swelling characteristics, kinetics of water release, amount and particle size of the SAPs will dictate their effectiveness for this purpose. In this paper, SAPs with different cross-linking degrees, particle sizes and amount of solubles are investigated. By varying these parameters, insight can be gained on the influence of each of these parameters on SAP properties such as the swelling capacity. In a next step, the SAPs can be implemented in mortar to assess their influence on mortar properties like workability, compressive strength or hydration kinetics. Based on these results, the ‘ideal’ SAP with tunable properties for a specific concrete application can be selected. For this purpose, an anionic SAP was synthesized with varying amounts of cross-linker and ground to particle sizes with d50 varying between 10 and 100 µm. The swelling capacity in demineralised water of 40 µm SAP particles increased with a decreasing degree of cross-linker from 66 g/g SAP with 1 mol% cross-linker to 270 g/g SAP in case of 0.15 mol% cross-linker, and was about three to four times larger than the swelling capacity in the prepared cement filtrate. The SAPs were tested for their effect on mortar workability, cement hydration kinetics and mechanical properties of the hardened mortar. With proper compensation for the absorbed water by the SAPs, the mortar workability was not negatively affected and the reduction in flow over the first two hours remained limited. The SAPs with the lowest swelling capacity, resulting in the smallest total amount of macro pores formed, showed the smallest negative effect on mortar compressive strength (a reduction of 23% compared to the reference after 28 days for an addition of 0.5 m% SAP) and a negligible effect on cement hydration. The difference in strength with the reference decreased as a function of mortar age. When using SAPs with particle sizes in the range of 10–100 µm, no significant differences between the studied particle sizes were found concerning the mortar properties. With the ease of upscaling in mind, the need to purify the SAPs and to remove the non-cross-linked soluble fraction was further investigated. It was shown that the solubles had no effect on the mortar properties, except for increasing the setting time with almost 100%.

Spatially isolated plant populations in agricultural landscapes exhibit genetic responses not only to habitat fragmentation per se but also to the composition of the landscape matrix between habitat patches. These responses can only be understood by examining how the landscape matrix influences among‐habitat movements of pollinators and seed vectors, which act as genetic linkers among populations. We studied the forest herb Polygonatum multiflorum and its associated pollinator and genetic linker, the bumblebee Bombus pascuorum, in three European agricultural landscapes. We aimed to identify which landscape features affect the movement activity of B. pascuorum between forest patches and to assess the relative importance of these features in explaining the forest herb's population genetic structure. We applied microsatellite markers to estimate the movement activity of the bumblebee as well as the population genetic structure of the forest herb. We modelled the movement activity as a function of various landscape metrics. Those metrics found to explain the movement activity best were then used to explain the population genetic structure of the forest herb. The bumblebee movement activity was affected by the cover of maize fields and semi‐natural grasslands on a larger spatial scale and by landscape heterogeneity on a smaller spatial scale. For some measures of the forest herb's population genetic structure, that is, allelic richness, observed heterozygosity and the F‐value, the combinations of landscape metrics, which explained the linker movement activity best, yielded lower AICc values than 95% of the models including all possible combinations of landscape metrics. Synthesis: The genetic linker, B. pascuorum, mediates landscape effects on the population genetic structure of the forest herb P. multiflorum. Our study indicates, that the movement of the genetic linker among forest patches, and thus the pollen driven gene flow of the herb, depends on the relative value of floral resources in the specific landscape setting. Noteworthy, the population genetic structure of the long‐lived, clonal forest herb species correlated with recent land‐use types such as maize, which have been existing for not more than a few decades within these landscapes. This underscores the short time in which land‐use changes can influence the evolutionary potential of long‐lived wild plants. Bumblebees can connect isolated populations of forest herbs within agricultural landscapes by moving between forest patches. These movements are influenced by specific aspects of the landscape. These same landscape aspects also partly explain the population genetic structure of a forest herb species associated with bumblebees as pollinators.

After all, how many times did you threaten her with remarks such as, ''If I ever learn that you slept with that guy, don't bother to come home again,'' or ''If you ever get pregnant, I swear I'll kill you both.'' THIS letter is fictitious, but hundreds of teen-age girls right here on Long Island, and thousands nationwide, find themselves in a situation similar to [Jane]'s each year. Along with drug abuse and suicide, pregnancy is one of the most serious problems facing teen-agers today. Accordingly, the question of abortion is no longer a private matter but rather a national political issue, with ''right to life'' and ''freedom to choose'' groups vilifying each other and unfortunately forgetting the root of the problem. A recent study by the National School Boards Association determined that teen- age pregnancy has reached ''epidemic proportions,'' that ''pregnant students just seem to disappear,'' that ''pregnancy remains the main reason why teens drop out of school'' and that, while ''gifted and talented students and the learning-disabled have advocacy groups, teen-age mothers are the forgotten many,'' a tragic loss of human potential to our society.