The DLBCL90 gene-expression assay identifies double-hit lymphomas with high sensitivity in patients from two phase II clinical trials with high-risk diffuse large B-cell lymphoma

Peer reviewe

Morphological factors of the central whorl leaf associated with leaf surface wetness and resistance in sorghum to shoot fly, Atherigona soccata

Earlier studies showed that leaf surface water on the central whorl leaf of sorghum seedlings is associated with resistance to shoot fly. In this study, the results of an experiment to determine if leaf surface wetness (LSW) originates from atmospheric condensation or from the plant are described. Morphological structures: trichomes, stomata, leaf cuticle and quantity of surface wax of the central whorl leaf were also examined for their role in LSW production. The results suggest that LSW of the central whorl leaf originates from the plant and is not due to condensation of atmospheric moisture. The presence of trichomes was indirectly associated with LSW and resistance to shoot fly but stomatal density was not associated with LSW production. The amount of wax extracted per 100 mg of fresh weight varied significantly between genotypes and seedling age. It was more in susceptible than in resistant genotypes; however, cuticular thickness was not associated with resistance. It is suggested that LSW could be the result of some form of cuticular movement of water to the leaf surface

UK Global Ocean GO6 and GO7: a traceable hierarchy of model resolutions

Versions 6 and 7 of the UK Global Ocean configuration (known as GO6 and GO7) will form the ocean components of the Met Office GC3.1 coupled model and UKESM1 earth system model to be used in CMIP61 simulations. The label “GO6” refers to a traceable hierarchy of three model configurations at nominal 1, 1∕4 and 1∕12° resolutions. The GO6 configurations are described in detail with particular focus on aspects which have been updated since the previous version (GO5). Results of 30-year forced ocean-ice integrations with the 1∕4° model are presented, in which GO6 is coupled to the GSI8.1 sea ice configuration and forced with CORE22 fluxes. GO6-GSI8.1 shows an overall improved simulation compared to GO5-GSI5.0, especially in the Southern Ocean where there are more realistic summertime mixed layer depths, a reduced near-surface warm and saline biases, and an improved simulation of sea ice. The main drivers of the improvements in the Southern Ocean simulation are tuning of the vertical and isopycnal mixing parameters. Selected results from the full hierarchy of three resolutions are shown. Although the same forcing is applied, the three models show large-scale differences in the near-surface circulation and in the short-term adjustment of the overturning circulation. The GO7 configuration is identical to the GO6 1∕4° configuration except that the cavities under the ice shelves are opened. Opening the ice shelf cavities has a local impact on temperature and salinity biases on the Antarctic shelf with some improvement in the biases in the Weddell Sea

Evaluating the physical and biogeochemical state of the global ocean component of UKESM1 in CMIP6 historical simulations

The ocean plays a key role in modulating the climate of the Earth system (ES). At the present time it is also a major sink both for the carbon dioxide (CO2) released by human activities and for the excess heat driven by the resulting atmospheric greenhouse effect. Understanding the ocean's role in these processes is critical for model projections of future change and its potential impacts on human societies. A necessary first step in assessing the credibility of such future projections is an evaluation of their performance against the present state of the ocean. Here we use a range of observational fields to validate the physical and biogeochemical performance of the ocean component of UKESM1, a new Earth system model (ESM) for CMIP6 built upon the HadGEM3-GC3.1 physical climate model. Analysis focuses on the realism of the ocean's physical state and circulation, its key elemental cycles, and its marine productivity. UKESM1 generally performs well across a broad spectrum of properties, but it exhibits a number of notable biases. Physically, these include a global warm bias inherited from model spin-up, excess northern sea ice but insufficient southern sea ice and sluggish interior circulation. Biogeochemical biases found include shallow remineralization of sinking organic matter, excessive iron stress in regions such as the equatorial Pacific, and generally lower surface alkalinity that results in decreased surface and interior dissolved inorganic carbon (DIC) concentrations. The mechanisms driving these biases are explored to identify consequences for the behaviour of UKESM1 under future climate change scenarios and avenues for model improvement. Finally, across key biogeochemical properties, UKESM1 improves in performance relative to its CMIP5 precursor and performs well alongside its fellow members of the CMIP6 ensemble

Resistance in sorghum to the shoot fly, Atherigona soccata: epicuticular wax and wetness of the central whorl leaf of young seedlings

Sorghum genotypes known to be resistant or susceptible to shoot fly, Atherigona soccata Rondani were examined by scanning electron microscopy for differences in epicuticular wax structure and wetness of the central leaf whorl. Two major types of wax structures were observed: shoot fly resistant and moderately resistant genotypes were characterised by a smooth amorphous wax layer and sparse wax crystals while susceptible genotypes possessed a dense meshwork of crystalline epicuticular wax. The density of wax crystals decreased from the third leaf to the seventh leaf stage and was related to both seedling age and leaf position. Water droplets on susceptible genotypes with dense wax crystals showed spreading at the edges indicating a tendency to wet easily. In resistant genotypes with less dense wax crystals the droplets remained intact and did not spread

In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells.

Translational research in bone tissue engineering is essential for “bench to bedside” patient benefit. However, the ideal combination of stem cells and biomaterial scaffolds for bone repair/regeneration is still unclear. The aim of this study is to investigate the osteogenic capacity of a combination of poly(DL-lactic acid) (PDLLA) porous foams containing 5 wt% and 40 wt% of Bioglass particles with human adipose-derived stem cells (ADSCs) in vitro and in vivo. Live/dead fluorescent markers, confocal microscopy and scanning electron microscopy showed that PDLLA/Bioglass porous scaffolds supported ADSC attachment, growth and osteogenic differentiation, as confirmed by enhanced alkaline phosphatase (ALP) activity. Higher Bioglass content of the PDLLA foams increased ALP activity compared with the PDLLA only group. Extracellular matrix deposition after 8 weeks in the in vitro cultures was evident by Alcian blue/Sirius red staining. In vivo bone formation was assessed by using scaffold/ADSC constructs in diffusion chambers transplanted intraperitoneally into nude mice and recovered after 8 weeks. Histological and immunohistochemical assays indicated significant new bone formation in the 40 wt% and 5 wt% Bioglass constructs compared with the PDLLA only group. Thus, the combination of a well-developed biodegradable bioactive porous PDLLA/Bioglass composite scaffold with a high-potential stem cell source (human ADSCs) could be a promising approach for bone regeneration in a clinical setting