Some extensions in continuous models for immunological correlates of protection

Detail of results of case-cohort investigation. (DOCX 41 kb

Sedimentological characterization of Antarctic moraines using UAVs and Structure-from-Motion photogrammetry

In glacial environments particle-size analysis of moraines provides insights into clast origin, transport history, depositional mechanism and processes of reworking. Traditional methods for grain-size classification are labour-intensive, physically intrusive and are limited to patch-scale (1m2) observation. We develop emerging, high-resolution ground- and unmanned aerial vehicle-based ‘Structure-from-Motion’ (UAV-SfM) photogrammetry to recover grain-size information across an moraine surface in the Heritage Range, Antarctica. SfM data products were benchmarked against equivalent datasets acquired using terrestrial laser scanning, and were found to be accurate to within 1.7 and 50mm for patch- and site-scale modelling, respectively. Grain-size distributions were obtained through digital grain classification, or ‘photo-sieving’, of patch-scale SfM orthoimagery. Photo-sieved distributions were accurate to <2mm compared to control distributions derived from dry sieving. A relationship between patch-scale median grain size and the standard deviation of local surface elevations was applied to a site-scale UAV-SfM model to facilitate upscaling and the production of a spatially continuous map of the median grain size across a 0.3 km2 area of moraine. This highly automated workflow for site scale sedimentological characterization eliminates much of the subjectivity associated with traditional methods and forms a sound basis for subsequent glaciological process interpretation and analysis

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes

Genetic assimilation of ancestral plasticity during parallel adaptation to Zinc contamination in Silene uniflora

Phenotypic plasticity in ancestral populations is hypothesized to facilitate adaptation, but evidence is piecemeal and often contradictory. Further, whether ancestral plasticity increases the probability of parallel adaptive changes has not been explored. The most general finding is that ancestral responses to a new environment are reversed following adaptation (known as reversion). We investigated the contribution of ancestral plasticity to adaptive evolution of gene expression in two independently evolved lineages of zinc-tolerant Silene uniflora. We found that the general pattern of reversion is driven by the absence of a widespread stress response in zinc-adapted plants compared with zinc-sensitive plants. We show that ancestral plasticity that moves expression closer to the optimum value in the new environment influences the evolution of gene expression among genes that are likely to be involved in adaptation and increases the chance that genes are recruited repeatedly during adaptation. However, despite convergence in gene expression levels between independently adapted lineages, ancestral plasticity does not influence how similar expression values of adaptive genes become. Surprisingly, we also observed that ancestral plasticity that increases fitness often becomes genetically determined and fixed, that is, genetically assimilated. These results emphasize the important role of ancestral plasticity in parallel adaptation

MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype.

BACKGROUND: MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression. RESULTS: Here we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed. CONCLUSION: This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Corrigendum to “The million-year evolution of the glacial trimline in the southernmost Ellsworth Mountains, Antarctica” [Earth and Planetary Science Letters 469 (2017) 42–52]

No abstract available

MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype

Integrated analysis of miRNA expression and genomic changes in human breast tumors allows the classification of tumor subtypes