Amino acid racemization reveals differential protein turnover in osteoarthritic articular and meniscal cartilages

INTRODUCTION: Certain amino acids within proteins have been reported to change from the L form to the D form over time. This process is known as racemization and is most likely to occur in long-lived low-turnover tissues such as normal cartilage. We hypothesized that diseased tissue, as found in an osteoarthritic (OA) joint, would have increased turnover reflected by a decrease in the racemized amino acid content. METHODS: Using high-performance liquid chromatography methods, we quantified the L and D forms of amino acids reported to racemize in vivo on a biological timescale: alanine, aspartate (Asp), asparagine (Asn), glutamate, glutamine, isoleucine, leucine (Leu), and serine (Ser). Furthermore, using a metabolically inactive control material (tooth dentin) and a control material with normal metabolism (normal articular cartilage), we developed an age adjustment in order to make inferences about the state of protein turnover in cartilage and meniscus. RESULTS: In the metabolically inactive control material (n = 25, ages 13 to 80 years) and the normal metabolizing control material (n = 19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu showed a significant change (increase) in racemization with age (P < 0.01). The age-adjusted proportions of racemized to total amino acid (D/D+L expressed as a percentage of the control material) for Asx, Ser, and Leu when compared with the normal articular cartilage control were 97%, 74%, and 73% in OA meniscal cartilage and 97%, 70%, and 78% in OA articular cartilage. We also observed lower amino acid content in OA articular and meniscal cartilages compared with normal articular cartilage as well as a loss of total amino acids with age in the OA meniscal but not the OA articular cartilage. CONCLUSIONS: These data demonstrate comparable anabolic responses for non-lesioned OA articular cartilage and OA meniscal cartilage but an excess of catabolism over anabolism for the meniscal cartilage

A matter of taste: the adverse effect of pollen compounds on the pre-ingestive gustatory experience of sugar solutions for honeybees

This is the final version. Available from the publisher via the DOI in this record.The online version of this article (https://doi.org/10.1007/s00359-019-01347-z) contains supplementary material, which is available to authorized users.In addition to sugars, nectar contains multiple nutrient compounds in varying concentrations yet little is known of their effect on the reward properties of nectar and the resulting implications for insect behaviour. We examined the pre-ingestive responses of honeybees to sucrose solutions containing a mix of pollen compounds, the amino acids proline or phenylalanine, or known distasteful substances, quinine and salt. We predicted that in taste and learning assays, bees would respond positively to the presence of nutrient compounds in a sucrose solution. However, bees’ proboscis extension responses decreased when their antennae were stimulated with pollen- or amino-acid supplemented sucrose solutions. Compared to pure sucrose, bees exhibited worse acquisition when conditioned to an odour with pollen-supplemented sucrose as the unconditioned stimulus. Such learning impairment was also observed with quinine-containing sucrose solutions. Our results suggest that bees can use their antennae to detect pollen compounds in floral nectars. Depending on the type and concentrations of compounds present, this may result in nectar being perceived as distasteful by bees, making it less effective in reinforcing the learning of floral cues. Such reward devaluation might be adaptive in cases where plants benefit from regulating the frequency of bee visitation.UKIERI (British Council)Biotechnology and Biological Sciences Research Council (BBSRC) (SWBiosciences DTP

Geometric representations for minimalist grammars

We reformulate minimalist grammars as partial functions on term algebras for strings and trees. Using filler/role bindings and tensor product representations, we construct homomorphisms for these data structures into geometric vector spaces. We prove that the structure-building functions as well as simple processors for minimalist languages can be realized by piecewise linear operators in representation space. We also propose harmony, i.e. the distance of an intermediate processing step from the final well-formed state in representation space, as a measure of processing complexity. Finally, we illustrate our findings by means of two particular arithmetic and fractal representations.Comment: 43 pages, 4 figure

Interference in Exclusive Vector Meson Production in Heavy Ion Collisions

Photons emitted from the electromagnetic fields of relativistic heavy ions can fluctuate into quark anti-quark pairs and scatter from a target nucleus, emerging as vector mesons. These coherent interactions are identifiable by final states consisting of the two nuclei and a vector meson with a small transverse momentum. The emitters and targets can switch roles, and the two possibilities are indistinguishable, so interference may occur. Vector mesons are negative parity so the amplitudes have opposite signs. When the meson transverse wavelength is larger than the impact parameter, the interference is large and destructive. The short-lived vector mesons decay before amplitudes from the two sources can overlap, and so cannot interfere directly. However, the decay products are emitted in an entangled state, and the interference depends on observing the complete final state. The non-local wave function is an example of the Einstein-Podolsky-Rosen paradox.Comment: 13 pages with 3 figures; submitted to Physical Review Letter

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Infection of hamsters with the UK Clostridium difficile ribotype 027 outbreak strain R20291

Clostridium difficile is the main cause of antibiotic-associated disease, a disease of high socio-economical importance that has recently been compounded by the global spread of the 027 (BI/NAP1/027) ribotype. C. difficile cases attributed to ribotype 027 strains have high recurrence rates (up to 36 %) and increased disease severity. The hamster model of infection is widely accepted as an appropriate model for studying aspects of C. difficile host–pathogen interactions. Using this model we characterized the infection kinetics of the UK 2006 outbreak strain, R20291. Hamsters were orally given a dose of clindamycin, followed 5 days later with 10 000 C. difficile spores. All 100 % of the hamsters succumbed to infection with a mean time to the clinical end point of 46.7 h. Colonization of the caecum and colon were observed 12 h post-infection reaching a maximum of approximately 3×104 c.f.u. per organ, but spores were not detected until 24 h post-infection. At 36 h post-infection C. difficile numbers increased significantly to approximately 6×107 c.f.u. per organ where numbers remained high until the clinical end point. Increasing levels of in vivo toxin production coincided with increases in C. difficile numbers in organs reaching a maximum at 36 h post-infection in the caecum. Epithelial destruction and polymorphonuclear leukocyte (PMN) recruitment occurred early on during infection (24 h) accumulating as gross microvilli damage, luminal PMN influx, and blood associated with mucosal muscle and microvilli. These data describe the fatal infection kinetics of the clinical UK epidemic C. difficile strain R20291 in the hamster infection model

Impact of the Mk VI SkinSuit on skin microbiota of terrestrial volunteers and an International Space Station-bound astronaut

Microgravity induces physiological deconditioning due to the absence of gravity loading, resulting in bone mineral density loss, atrophy of lower limb skeletal and postural muscles, and lengthening of the spine. SkinSuit is a lightweight compression suit designed to provide head-to-foot (axial) loading to counteract spinal elongation during spaceflight. As synthetic garments may impact negatively on the skin microbiome, we used 16S ribosomal RNA (rRNA) gene amplicon procedures to define bacterial skin communities at sebaceous and moist body sites of five healthy male volunteers undergoing SkinSuit evaluation. Each volunteer displayed a diverse, distinct bacterial population at each skin site. Short (8 h) periods of dry hyper-buoyancy flotation wearing either gym kit or SkinSuit elicited changes in the composition of the skin microbiota at the genus level but had little or no impact on community structure at the phylum level or the richness and diversity of the bacterial population. We also determined the composition of the skin microbiota of an astronaut during pre-flight training, during an 8-day visit to the International Space Station involving two 6–7 h periods of SkinSuit wear, and for 1 month after return. Changes in composition of bacterial skin communities at five body sites were strongly linked to changes in geographical location. A distinct ISS bacterial microbiota signature was found which reversed to a pre-flight profile on return. No changes in microbiome complexity or diversity were noted, with little evidence for colonisation by potentially pathogenic bacteria; we conclude that short periods of SkinSuit wear induce changes to the composition of the skin microbiota but these are unlikely to compromise the healthy skin microbiome