The ability of land plants to synthesize glucuronoxylans predates the evolution of tracheophytes

Glucuronoxylans with a backbone of 1,4-linked β-D-xylosyl residues are ubiquitous in the secondary walls of gymnosperms and angiosperms. Xylans have been reported to be present in hornwort cell walls, but their structures have not been determined. In contrast, the presence of xylans in the cell walls of mosses and liverworts remains a subject of debate. Here we present data that unequivocally establishes that the cell walls of leafy tissue and axillary hair cells of the moss Physcomitrella patens contain a glucuronoxylan that is structurally similar to glucuronoxylans in the secondary cell walls of vascular plants. Some of the 1,4-linked β-D-xylopyranosyl residues in the backbone of this glucuronoxylan bear an α-D-glucosyluronic acid (GlcpA) sidechain at O-2. In contrast, the lycopodiophyte Selaginella kraussiana synthesizes a glucuronoxylan substituted with 4-O-Me-α-D-GlcpA sidechains, as do many hardwood species. The monilophyte Equisetum hyemale produces a glucuronoxylan with both 4-O-Me-α-D-GlcpA and α-D-GlcpA sidechains, as does Arabidopsis. The seedless plant glucuronoxylans contain no discernible amounts of the reducing-end sequence that is characteristic of gymnosperm and eudicot xylans. Phylogenetic studies showed that the P. patens genome contains genes with high sequence similarity to Arabidopsis CAZy family GT8, GT43 and GT47 glycosyltransferases that are likely involved in xylan synthesis. We conclude that mosses synthesize glucuronoxylan that is structurally similar to the glucuronoxylans present in the secondary cell walls of lycopodiophytes, monilophytes, and many seed-bearing plants, and that several of the glycosyltransferases required for glucuronoxylan synthesis evolved before the evolution of tracheophytes.     

Lead optimisation of pyrazoles as novel FPR1 antagonists

Optimisation of a series of pyrazole inhibitors of the human FPR1 receptor has been achieved. The use of an in vitro media loss assay was utilised to identify sub-series with more robust DMPK profiles. These were subsequently improved to generate analogues with attractive overall profiles.     

Synthesis and SAR of selective small molecule neuropeptide Y Y2 receptor antagonists

Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC(50) values of 19 nM and 12 nM respectively.     

Chilling-induced ultrastructural changes to mesophyll cells of Arabidopsis grown under short days are almost completely reversible by plant re-warming

Exposure of plants to chilling (low temperatures above freezing) limits growth and development in all environments outside the lowest latitudes. Cell ultrastructure and morphometric studies may allow associations to be made between chilling-induced changes at the ultrastructural level, molecular events and their physiological consequences. We examined changes in the shape, size and membrane organization of the organelles of mesophyll cells in Arabidopsis thaliana (Col 0), a cold-resistant species, after subjecting 6-week-old plants grown at normal growth temperatures to chilling (2.5–4°C; 14-h dark/10-h light cycle) for 6, 24 and 72 h and after a re-warming period of 50 h. No ultrastructural differences were seen in the first 6 h of chilling but after 24 h we observed swollen and rounded chloroplasts with larger starch grains and dilated thylakoids compared to control plants. By 72 h, chilling had resulted in a large accumulation of starch in chloroplasts, an apparent crowding of the cytosol and a lower abundance of peripheral reticulum than in the controls. The average area per chloroplast in cell sections increased after 72-h chilling while the number of chloroplasts remained the same. Ring-shaped and other morphologically aberrant mitochondria were present in significantly higher abundance in plants given 72 h chilling than in the controls. Plant re-warming for 50 h reduced chloroplast size to those of the controls and returned mitochondria to standard morphology, but peripheral reticulum remained less abundant than in plants never given a cold treatment. The near full return to normal ultrastructure upon plant re-warming indicates that the morphological changes may be part of acclimation to cold.     

New ages for Middle and Later Stone Age deposits at Mumba rockshelter, Tanzania: optically stimulated luminescence dating of quartz and feldspar grains

The archaeological deposits at Mumba rockshelter, northern Tanzania, have been excavated for more than 70 years, starting with Margit and Ludwig Köhl-Larsen in the 1930s. The assemblages of Middle Stone Age (MSA) and Later Stone Age (LSA) artefacts collected from this site constitute the type sequences for these cultural phases in East Africa. Despite its archaeological importance, however, the chronology of the site is poorly constrained, despite the application since the 1980s of several dating methods (radiocarbon, uranium-series and amino acid racemisation) to a variety of materials recovered from the deposits. Here, we review these previous chronologies for Mumba and report new ages obtained from optically stimulated luminescence (OSL) and infrared stimulated luminescence (IRSL) measurements on single grains of quartz and multi-grain aliquots of potassium (K) feldspar from the MSA and LSA deposits. Measurements of single grains of quartz allowed the rejection of unrepresentative grains and the application of appropriate statistical models to obtain the most reliable age estimates, while measurements of K-feldspars allowed the chronology to be extended to older deposits. The seven quartz ages and four K-feldspar ages provide improved temporal constraints on the archaeological sequence at Mumba. The deposits associated with the latest Kisele Industry (Bed VI-A) and the earliest Mumba Industry (Bed V) are dated to 63.4 ± 5.7 and 56.9 ± 4.8 ka (thousands of years ago), respectively, thus constraining the time of transition between these two archaeological phases to ∼60 ka. An age of 49.1 ± 4.3 ka has been obtained for the latest deposits associated with the Mumba Industry, which show no evidence for post-depositional mixing and contain ostrich eggshell (OES) beads and abundant microlithics. The Nasera Industry deposits (Bed III) contain large quantities of OES beads and date to 36.8 ± 3.4 ka. We compare the luminescence ages with the previous chronologies for Mumba, and briefly discuss how the revised chronology fits in the context of existing archaeological records and palaeoclimatic reconstructions for East Africa.     

Relationship satisfaction and outcome in women who meet their partner while using oral contraception

Hormonal variation over the menstrual cycle alters women's preferences for phenotypic indicators of men's genetic or parental quality. Hormonal contraceptives suppress these shifts, inducing different mate preference patterns among users and non-users. This raises the possibility that women using oral contraception (OC) choose different partners than they would do otherwise but, to date, we know neither whether these laboratory-measured effects are sufficient to exert real-world consequences, nor what these consequences would be. Here, we test for differences in relationship quality and survival between women who were using or not using OC when they chose the partner who fathered their first child. Women who used OC scored lower on measures of sexual satisfaction and partner attraction, experienced increasing sexual dissatisfaction during the relationship, and were more likely to be the one to initiate an eventual separation if it occurred. However, the same women were more satisfied with their partner's paternal provision, and thus had longer relationships and were less likely to separate. These effects are congruent with evolutionary predictions based on cyclical preference shifts. Our results demonstrate that widespread use of hormonal contraception may contribute to relationship outcome, with implications for human reproductive behaviour, family cohesion and quality of life.     

Muscle power attenuation by tendon during energy dissipation

An important function of skeletal muscle is deceleration via active muscle fascicle lengthening, which dissipates movement energy. The mechanical interplay between muscle contraction and tendon elasticity is critical when muscles produce energy. However, the role of tendon elasticity during muscular energy dissipation remains unknown. We tested the hypothesis that tendon elasticity functions as a mechanical buffer, preventing high (and probably damaging) velocities and powers during active muscle fascicle lengthening. We directly measured lateral gastrocnemius muscle force and length in wild turkeys during controlled landings requiring rapid energy dissipation. Muscle-tendon unit (MTU) strain was measured via video kinematics, independent of muscle fascicle strain (measured via sonomicrometry). We found that rapid MTU lengthening immediately following impact involved little or no muscle fascicle lengthening. Therefore, joint flexion had to be accommodated by tendon stretch. After the early contact period, muscle fascicles lengthened and absorbed energy. This late lengthening occurred after most of the joint flexion, and was thus mainly driven by tendon recoil. Temporary tendon energy storage led to a significant reduction in muscle fascicle lengthening velocity and the rate of energy absorption. We conclude that tendons function as power attenuators that probably protect muscles against damage from rapid and forceful lengthening during energy dissipation.     

Using metalloproteomics to investigate the cellular physiology of copper in hepatocytes

Proteomics is a systems biology approach for examining proteins and their function in a given specified system. Metalloproteomics narrows the focus of proteomics to those proteins which bind a metal or are metalloproteins. An important system where metalloproteomics can be applied is the hepatocyte, the liver's parenchymal cell engaged in protein synthesis, nutrient deployment, and drug biotransformation. Hepatocellular metalloproteomics is an exciting new scientific discipline which has already advanced our understanding of certain genetic and neoplastic liver disorders. It has the potential to elucidate the action of numerous metals in hepatocytes and generate new diagnostic parameters, namely, novel biomarkers.