New insights into the population biology of endoparasitic Rafflesiaceae

Parasitic plants demonstrate a diversity of growth strategies, life histories, and developmental and physiological characteristics. Most research to date has focused on a narrow range of parasitic taxa, particularly in the Orobanchaceae, while the other independent origins of parasitism have largely gone unstudied. One type of parasite that has received relatively little attention are the endophytic parasites, which have a fascinating growth strategy where the parasite is embedded within the host tissue, with the flower the only externally visibly plant part. Endophytic growth makes it challenging to understand basic aspects of species biology, such as the size of a given parasite, the number of parasites per host, and the genetic diversity of populations. Recent studies by Barkman et al. (2017) and Pelser et al. (2017) have used microsatellite genotyping to investigate the population biology of endoparasitic Rafflesiaceae species in Asia. They show the potential for extensive parasite spread within a host vine and the strong partitioning of genetic diversity by host. These species are also shown to have an outcrossing mating system. However, these studies suggest different reproductive strategies, one supporting monoecy and one suggesting dioecy. Overall, these studies partly “lift the lid” on the cryptic biology of Rafflesia and the Rafflesiaceae and open the door for future comparative studies between endophytic and free-living parasitic plants.     

The Duplexing of the Genetic Code and Sequence-Dependent DNA Geometry

It is well known that sequences of bases in DNA are translated into sequences of amino acids in cells via the genetic code. More recently, it has been discovered that the sequence of DNA bases also influences the geometry and deformability of the DNA. These two correspondences represent a naturally arising example of duplexed codes, providing two different ways of interpreting the same DNA sequence. This paper will set up the notation and basic results necessary to mathematically investigate the relationship between these two natural DNA codes. It then undertakes two very different such investigations: one graphical approach based only on expected values and another analytic approach incorporating the deformability of the DNA molecule and approximating the mutual information of the two codes. Special emphasis is paid to whether there is evidence that pressure to maximize the duplexing efficiency influenced the evolution of the genetic code. Disappointingly, the results fail to support the hypothesis that the genetic code was influenced in this way. In fact, applying both methods to samples of realistic alternative genetic codes shows that the duplexing of the genetic code found in nature is just slightly less efficient than average. The implications of this negative result are considered in the final section of the paper.     

A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

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Design,synthesis, and biological evaluation of novel selective peptide inhibitors of 11β-hydroxysteroid dehydrogenase 1

The enzyme 11β-HSD1 plays a crucial role in the tissue-specific regulation of cortisol levels and it has been associated with various diseases. Inhibition of 11β-HSD1 is an attractive intervention strategy and the discovery of novel selective 11β-HSD1 inhibitors is of high relevance. In this study, we identified and evaluated a new series of selective peptide 11β-HSD1 inhibitors with potential for skin care applications. This novel scaffold was designed with the aid of molecular modeling and two previously reported inhibitors. SAR optimization yielded highly active peptides (IC₅₀ below 400?nM) that were inactive at 1?µM concentration against structurally related enzymes (11β-HSD2, 17β-HSD1 and 17β-HSD2). The best performing peptides inhibited the conversion of cortisone into cortisol in primary human keratinocytes and the most active compound, 5d, was further shown to reverse cortisone-induced collagen damage in human ex-vivo tissue.     

Trait differentiation and adaptation of plants along elevation gradients

Studies of genetic adaptation in plant populations along elevation gradients in mountains have a long history, but there has until now been neither a synthesis of how frequently plant populations exhibit adaptation to elevation nor an evaluation of how consistent underlying trait differences across species are. We reviewed studies of adaptation along elevation gradients (i) from a meta‐analysis of phenotypic differentiation of three traits (height, biomass and phenology) from plants growing in 70 common garden experiments; (ii) by testing elevation adaptation using three fitness proxies (survival, reproductive output and biomass) from 14 reciprocal transplant experiments; (iii) by qualitatively assessing information at the molecular level, from 10 genomewide surveys and candidate gene approaches. We found that plants originating from high elevations were generally shorter and produced less biomass, but phenology did not vary consistently. We found significant evidence for elevation adaptation in terms of survival and biomass, but not for reproductive output. Variation in phenotypic and fitness responses to elevation across species was not related to life history traits or to environmental conditions. Molecular studies, which have focussed mainly on loci related to plant physiology and phenology, also provide evidence for adaptation along elevation gradients. Together, these studies indicate that genetically based trait differentiation and adaptation to elevation are widespread in plants. We conclude that a better understanding of the mechanisms underlying adaptation, not only to elevation but also to environmental change, will require more studies combining the ecological and molecular approaches.