Human CD23: Is It a Lectin in Disguise?

The crystal structure of a low-affinity human IgE receptor, CD23, is reported by Wurzburg et al. (2006) in this issue of Structure. This, together with a similar NMR structure by Hibbert et al. (2005) provide some insights into the function of the receptor

The Structural Basis of Ligand Recognition by Natural Killer Cell Receptors

Natural killer cells are a group of lymphocytes which function as tightly controlled surveillance operatives which identify transformed cells through a discrete balance of activating and inhibitory receptors ultimately leading to the destruction of incongruent cells. The understanding of this finely tuned balancing act has been aided by the high-resolution structure determination of activating and inhibitory receptors both alone and in complex with their ligands. This paper collates these structural studies detailing the aspects which directly relate to the natural killer cell function and serves to inform both the specialized structural biologist reader and a more general immunology audience

HoxA9 binds and represses the Cebpa +8 kb enhancer

C/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9

The development of a ε-polycaprolactone (PCL) scaffold for CNS repair

Potential treatment strategies for the repair of spinal cord injury (SCI) currently favour a combinatorial approach incorporating several factors, including exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds for bridging the gap at the injury site is very appealing although there has been little investigation into CNS neural cell interaction and survival on such scaffolds before implantation. Previously we demonstrated that aligned micro-grooves 12.5-25 µm wide on ε-polycaprolactone (PCL) promoted aligned neurite orientation and supported myelination. In this study we identify the appropriate substrate and its topographical features required for the design of a 3D scaffold intended for transplantation in SCI. Using an established myelinating culture system of dissociated spinal cord cells, recapitulating many of the features of the intact spinal cord, we demonstrate that astrocytes plated on the topography secrete soluble factors(s) that delay oligodendrocyte differentiation but do not prevent myelination. However, as myelination does occur after a further 10-12 days in culture this does not prevent the use of PCL as a scaffold material as part of a combined strategy for the repair of SCI

Response of terrestrial net primary productivity (NPPT) in the Wujiang catchment (China) to the construction of cascade hydropower stations

The damming of rivers results in hydrological modifications that not only affect the aquatic ecosystem but also adjoining terrestrial systems. Thirteen dams commissioned along the Wujiang River have induced ecological problems, including decreased water turbidity and loss of biodiversity, which potentially influence ecosystem net primary production (NPP) and hence the sequestration, transformation, and storage of carbon. We used terrestrial NPP (NPPT) as a bioindicator to assess the impact of dams on carbon storage in the Wujiang catchment. MODIS satellite and meteorological data were used as inputs to the CASA model to calculate annual NPPT from 2000 to 2014. NPPT was calculated at the catchment and landscape scale to quantify the impact of dams on surrounding terrestrial ecosystems. Mean NPPT was calculated for concentric buffer zones covering a range of spatial extents (0–10 km) from the reservoir shoreline. We found a negligible impact from construction of a single dam on NPPT at the catchment scale. By contrast, the impact of dam construction was scale-dependent, with a stronger landscape-scale effect observed at short distances (i.e., 0–1 km) from the reservoir. Decreases in NPPT were mainly ascribed to the loss of vegetated land resulting from dam impoundment and subsequent urbanization of the surrounding area

Lake and catchment-scale determinants of aquatic vegetation across almost 1,000 lakes and the contrasts between lake types

Aim The factors controlling macrophyte (aquatic plant) composition are complex, recent research having shown that the well-studied effects of lake environmental factors (the so-called “environmental filter”) can be constrained by hydrological and landscape factors. We investigated the factors determining macrophyte composition in lakes over water body and catchment- scales and the transferability of this pattern across lake types. Location Almost 1000 lakes distributed across Britain. Taxon Lake macrophytes Methods Lakes were partitioned into five types based on subdivision of alkalinity and elevation gradients. Data from botanical surveys were used to compare the spatial turnover and nestedness components of beta diversity between lake types. The relative importance of lake environment (based on local physicochemical data), hydrology (e.g. lake and stream density), landscape (e.g. fragmentation indices, land cover) and spatial autocorrelation in explaining variation in macrophyte composition were derived from variance partitioning. Results Species composition showed strong spatial structuring, suggestive of overland dispersal, enhanced by spatially-correlated abiotic factors such as alkalinity and elevation. Catchment-scale factors (e.g. land use, connectivity) promoted the establishment of different communities (more or less diverse, or differing in composition) but were of secondary importance. Turnover in composition between upland lakes was lower than in other lake types, reflecting a more specialist flora and increased potential for propagule exchange due to spatial aggregation and higher hydrological connectivity. Main conclusions Vegetation composition in lakes is more spatially-structured than previously appreciated, consistent with the importance of dispersal limitation, but this does not apply evenly to all lakes, being most acute in lowland high alkalinity lakes. Thus, spatially-structured abiotic factors, such as alkalinity, influence macrophyte composition most (suggestive of niche filtering) in high alkalinity lakes where human impacts tend to be greatest, although nestedness was also lowest in such lakes. By contrast, hydrological connectivity has a proportionally stronger structuring role in upland lakes

A rational approach to heavy-atom derivative screening

In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification

Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since we use CNS myelinating cultures, we can confirm that the scaffold does not affect neural cell differentiation. It was found that heterogeneous cell distribution within the tubular constructs was caused by a combination of gravity, fluid flow, topography, and scaffold configuration, while cell survival was influenced by scaffold length, porosity, and thickness. This research demonstrates that the mini-chambers represent a viable, novel, scale down approach for the evaluation of complex 3D scaffolds as well as providing a microbioprocessing strategy for tissue engineering and the potential repair of SCI