Modelling fixed plant and algal dynamics in rivers: an application to the River Frome

The development of eutrophication in river systems is poorly understood given the complex relationship between fixed plants, algae, hydrodynamics, water chemistry and solar radiation. However there is a pressing need to understand the relationship between the ecological status of rivers and the controlling environmental factors to help the reasoned implementation of the Water Framework Directive and Catchment Sensitive Farming in the UK. This research aims to create a dynamic, process-based, mathematical in-stream model to simulate the growth and competition of different vegetation types (macrophytes, phytoplankton and benthic algae) in rivers. The model, applied to the River Frome (Dorset, UK), captured well the seasonality of simulated vegetation types (suspended algae, macrophytes, epiphytes, sediment biofilm). Macrophyte results showed that local knowledge is important for explaining unusual changes in biomass. Fixed algae simulations indicated the need for the more detailed representation of various herbivorous grazer groups, however this would increase the model complexity, the number of model parameters and the required observation data to better define the model. The model results also highlighted that simulating only phytoplankton is insufficient in river systems, because the majority of the suspended algae have benthic origin in short retention time rivers. Therefore, there is a need for modelling tools that link the benthic and free-floating habitats

Second-harmonic generation microscopy analysis reveals proteoglycan decorin is necessary for proper collagen organization in prostate.

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn  -    /    -  ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to the SHG coherence length, and found more disordered fibril organization in the Dcn  -    /    -  . We have also used image analysis readouts based on entropy, multifractal dimension, and wavelet transforms to compare the collagen fibril/fiber architecture in the two models, where all these showed that the Dcn  -    /    -   prostate comprised smaller and more disorganized collagen structures. All these SHG metrics are consistent with decreased SHG phase matching in the Dcn  -    /    -   and are further consistent with ultrastructural analysis of collagen in this model in other tissues, which show a more random distribution of fibril sizes and their packing into fibers. As Dcn is a known tumor suppressor, this work forms the basis for future studies of collagen remodeling in both malignant and benign prostate disease

The Transcription Factors Snail and Slug Activate the Transforming Growth Factor-Beta Signaling Pathway in Breast Cancer

The transcriptional repressors Snail and Slug are situated at the core of several signaling pathways proposed to mediate epithelial to mesenchymal transition or EMT, which has been implicated in tumor metastasis. EMT involves an alteration from an organized, epithelial cell structure to a mesenchymal, invasive and migratory phenotype. In order to obtain a global view of the impact of Snail and Slug expression, we performed a microarray experiment using the MCF-7 breast cancer cell line, which does not express detectable levels of Snail or Slug. MCF-7 cells were infected with Snail, Slug or control adenovirus, and RNA samples isolated at various time points were analyzed across all transcripts. Our analyses indicated that Snail and Slug regulate many genes in common, but also have distinct sets of gene targets. Gene set enrichment analyses indicated that Snail and Slug directed the transcriptome of MCF-7 cells from a luminal towards a more complex pattern that includes many features of the claudin-low breast cancer signature. Of particular interest, genes involved in the TGF-beta signaling pathway are upregulated, while genes responsible for a differentiated morphology are downregulated following Snail or Slug expression. Further we noticed increased histone acetylation at the promoter region of the transforming growth factor beta-receptor II (TGFBR2) gene following Snail or Slug expression. Inhibition of the TGF-beta signaling pathway using selective small-molecule inhibitors following Snail or Slug addition resulted in decreased cell migration with no impact on the repression of cell junction molecules by Snail and Slug. We propose that there are two regulatory modules embedded within EMT: one that involves repression of cell junction molecules, and the other involving cell migration via TGF-beta and/or other pathways

The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties

The methyl-CpG binding domain (MBD) family of proteins was defined based on sequence similarity in their DNA binding domains. In light of their high degree of conservation, it is of inherent interest to determine the genomic distribution of these proteins, and their associated co-repressor complexes. One potential determinant of specificity resides in differences in the intrinsic DNA binding properties of the various MBD proteins. In this report, we use a capillary electrophoretic mobility shift assay (CEMSA) with laser-induced fluorescence (LIF) and neutral capillaries to calculate MBD-DNA binding affinities. MBD proteins were assayed on pairs of methylated and unmethylated duplex oligos corresponding to the promoter regions of the BRCA1, MLH1, GSTP1 and p16(INK4a) genes, and binding affinities for each case were calculated by Scatchard analyses. With the exception of mammalian MBD3 and Xenopus MBD3 LF, all the MBD proteins showed higher affinity for methylated DNA (in the nanomolar range) than for unmethylated DNA (in the micromolar range). Significant differences between MBD proteins in the affinity for methylated DNA were observed, ranging within two orders of magnitude. By mutational analysis of MBD3 and using CEMSA, we demonstrate the critical role of specific residues within the MBD in conferring selectivity for methylated DNA. Interestingly, the binding affinity of specific MBD proteins for methylated DNA fragments from naturally occurring sequences are affected by local methyl-CpG spacing

Pelvic Positioning in the Supine Position Leads to More Consistent Cup Orientation after Total Hip Arthroplasty

Aims: This study aims to 1) Determine the difference in pelvic position that occurs between surgery and radiographic, supine, post-operative assessment; 2) Examine how the difference in pelvic position influences subsequent cup orientation and 3) Establish whether pelvic position, and thereafter cup orientation differences exist between THAs performed in the supine versus the lateral decubitus positions. Materials and Methods: 321 THAs who had intra-operative, post-cup impaction, AP pelvic radiograph, in the operative position were studied; 167 were performed with patient supine (anterior approach), whilst 154 were performed in lateral decubitus (posterior approach). Cup inclination/anteversion was measured from intra- and post-operative radiographs and difference (Δ) was determined. The target zone was inclination/anteversion of 40/20°±10°. Change in pelvic position (tilt, rotation, obliquity) between surgery and post-operatively was calculated from Δinclination/anteversion using the Levenberg-Marquardt algorithm. Results: The post-operative inclination/anteversion was 40°±8/23°±9. 74 had Δinclination and/or Δanteversion>±10° (21%). Intra-operatively (compared to post-operative), the pelvis was on average 4°±10 anteriorly tilted; 1°±10 internally rotated and 1°±5 adducted. Having Δinclination and/or Δanteversion >±10° was associated with a 3.5 odds ratio of having a cup outside the target. A greater proportion of hips operated in the lateral decubitus had Δinclination and/or Δanteversion >±10° (54/153), compared to supine (8/167) (p<0.001). A greater number of cups achieved the target orientation in supine (120/167;73%), compared to lateral position (67/153;44%) (p<0.001). Intra-operatively, pelvis was more anteriorly tilted (p<0.001) and hemi-pelvis was more internally rotated (p=0.04) in lateral position. Conclusion: Pelvic movement is significantly less in supine position, which leads to more consistent cup orientation. Significant differences in pelvic tilt and rotation were seen in the lateral position. Clinical Relevance: Understanding the differences in pelvic orientation and cup orientation between supine and lateral decubitus positions may facilitate better intraoperative practices for surgeons

Oligocene chronostratigraphy and planktonic foraminiferal biostratigraphy: historical review and current state-of-the art

We review past and recent advances in Oligocene chronostratigraphy (and its internal subdivisions) and geochronology, the so-called “missing” Oligocene debate of the 1960s, and planktonic foraminiferal biostratigraphies of (sub)tropical and austral biogeographies. The Oligocene spans the interval from Chron C13r.0.14 to Subchron C6Cn.2n(o), corresponding to astronomical cycles 84Ol-C13n to 58OlC6Cn. It is currently subdivided into two (Rupelian and Chattian) ages/stages. The planktonic foraminiferal biostratigraphy is characterized by a 7-fold (sub) tropical and 4-fold austral zonation, respectively

Navy Force Structure Review Strategic Risk Workshop and Technology Review

NPS NRP Project PosterThe study's goal is to comparatively evaluate combat effectiveness of the planned Fleet Design with a novel alternative design against potential global adversaries in the 2040 timeframe. Insights and recommendations from the study will be used in the next Force Structure Assessment and the FY 2024 30-Year Shipbuilding Plan.N8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.

Navy Force Structure Review Strategic Risk Workshop and Technology Review

NPS NRP Executive SummaryThe study's goal is to comparatively evaluate combat effectiveness of the planned Fleet Design with a novel alternative design against potential global adversaries in the 2040 timeframe. Insights and recommendations from the study will be used in the next Force Structure Assessment and the FY 2024 30-Year Shipbuilding Plan.N8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.