Cell Therapy for Type 1 Diabetes

Acknowledgements The work described in this review was supported by a grant from the MRC. K.R.M. is supported by a fellowship from the Scottish Translational Medicines and Therapeutics Initiative through the Wellcome Trust.Peer reviewedPublisher PD

Trafficking and processing of bacterial proteins by mammalian cells: Insights from chondroitinase ABC.

Background: There is very little reported in the literature about the relationship between modifications of bacterial proteins and their secretion by mammalian cells that synthesize them. We previously reported that the secretion of the bacterial enzyme Chondroitinase ABC by mammalian cells requires the strategic removal of at least three N-glycosylation sites. The aim of this study was to determine if it is possible to enhance the efficacy of the enzyme as a treatment for spinal cord injury by increasing the quantity of enzyme secreted or by altering its cellular location. Methodology/principal findings: To determine if the efficiency of enzyme secretion could be further increased, cells were transfected with constructs encoding the gene for chondroitinase ABC modified for expression by mammalian cells; these contained additional modifications of strategic N-glycosylation sites or alternative signal sequences to direct secretion of the enzyme from the cells. We show that while removal of certain specific N-glycosylation sites enhances enzyme secretion, N-glycosylation of at least two other sites, N-856 and N-773, is essential for both production and secretion of active enzyme. Furthermore, we find that the signal sequence directing secretion also influences the quantity of enzyme secreted, and that this varies widely amongst the cell types tested. Last, we find that replacing the 3’UTR on the cDNA encoding Chondroitinase ABC with that of β-actin is sufficient to target the enzyme to the neuronal growth cone when transfected into neurons. This also enhances neurite outgrowth on an inhibitory substrate. Conclusion/significance: Some intracellular trafficking pathways are adversely affected by cryptic signals present in the bacterial gene sequence, whilst unexpectedly others are required for efficient secretion of the enzyme. Furthermore, targeting chondroitinase to the neuronal growth cone promotes its ability to increase neurite outgrowth on an inhibitory substrate. These findings are timely in view of the renewed prospects for gene therapy, and of direct relevance to strategies aimed at expressing foreign proteins in mammalian cells, in particular bacterial proteins

From Neural Arbors to Daisies

Pyramidal neurons in layers 2 and 3 of the neocortex collectively form an horizontal lattice of long-range, periodic axonal projections, known as the superficial patch system. The precise pattern of projections varies between cortical areas, but the patch system has nevertheless been observed in every area of cortex in which it has been sought, in many higher mammals. Although the clustered axonal arbors of single pyramidal cells have been examined in detail, the precise rules by which these neurons collectively merge their arbors remain unknown. To discover these rules, we generated models of clustered axonal arbors following simple geometric patterns. We found that models assuming spatially aligned but independent formation of each axonal arbor do not produce patchy labeling patterns for large simulated injections into populations of generated axonal arbors. In contrast, a model that used information distributed across the cortical sheet to generate axonal projections reproduced every observed quality of cortical labeling patterns. We conclude that the patch system cannot be built during development using only information intrinsic to single neurons. Information shared across the population of patch-projecting neurons is required for the patch system to reach its adult stat

The United States in Pending World Trade Negotiations

The United States emerged from World War II as the only major trading nation with a strong economic and financial position. The post-War international trading structure, embodied in the General Agreement on Tariffs and Trade (GATT) and the International Monetary Fund (IMF) frameworks, was established with the United States in the position of a dominant, largely self--sufficient producer of many and superior goods. The succeeding three decades, however, have witnessed radical changes in that circumstance. No longer is a fortress America economically feasible. The United States is no longer self-sufficient in a number of raw materials on which it depends; indeed, the scarcity of natural resources may well be one of the dominating issues for the next decade, if not for the remainder of the century. More than one study has predicted acute shortages of basic agricultural, mineral, and other industrial materials in coming decades. While technological improvements and the cultivation of substitutes for some materials may alleviate shortages, the problem of resource scarcity is still serious, and the effects of a variety of shortage situations are already being felt. State officials contemplate the possibility of Texas becoming a net importer of petroleum within five years. World food production is being pushed to capacity. Demand curves, moreover, following population curves and increased consumption by the Third World, must inevitably increase the strain on stable markets. Substantial increases in costs--reflecting in large part a real increase in commodity value through decreased supply, increased demand or increased costs of production--seem unavoidable and already apparent

Growing communities through nature: research report

This is the final version.Growing Communities Through Nature was designed to test models for community engagement in co-production and local innovation, following this up with co-designed and co-delivered maintenance, monitoring and evaluation activity. The research team investigated the impact of using three different institutional vehicles for bringing together communities around local activity. The project worked in three Cornish towns - Launceston, Helston and Newquay - to run workshops co-designing public open spaces in collaboration with a number of partners. The workshops aimed to bring people together to share ideas about an existing space and its potential improvement, discuss new designs for the site and how to maintain the space, as well as monitoring and evaluating its impact on biodiversity and the local community. In addition to the benefits of climate change mitigation, the development of deeper working relationships between the University, partner organisations and the public provides a blueprint for further integration between higher education institutions and communities. Experience of using co-design, co-delivery and co-monitoring methods and tools provides a foundation from which the partners can develop future place-based activities to respond to a range of needs and challenges (such as community development and housing schemes). This approach could also be scaled-up to other Cornish towns and villages via larger collaborative funding applications. This research report documents the project, peoples’ experiences and the wider implications.UKR

Black medics from Texas

Last updated: 10/22/201

Medics and clovers for the Cross Timbers

Last updated: 10/22/201

Annual Forage Legume Response to Herbicides Labelled for Lucerne Establishment

Weed competition reduces stand establishment, thus lowering forage production and quality. However, there are no herbicides labelled for annual legume establishment, despite several labelled for the establishment of lucerne (Medicago sativa). Some of these may be useful in the establishment and production of annual forage legumes. Lucerne herbicides have greater potential for use on other legumes, since they have grazing and feeding clearance. The objective of this paper is to summarize annual legume yield response trials to herbicides labelled for lucerne establishment

Review of the initial validation and characterization of a chicken 3K SNP array.

In 2004 the chicken genome sequence and more than 2.8 million single nucleotide polymorphisms (SNPs) were reported. This information greatly enhanced the ability of poultry scientists to understand chicken biology, especially with respect to identification of quantitative trait loci (QTL) and genes that control simple and complex traits. To validate and address the quality of the reported SNPs, assays for 3072 SNPS were developed and used to genotype 2576 DNAs isolated from commercial and experimental birds. Over 90% of the SNPs were valid based on the criterion used for segregating, and over 88% had a minor allele frequency of 2% or greater. As the East Lansing (EL) and Wageningen University (WAU) reference panels were genotyped, 1933 SNPs were added to the chicken genetic map, which was used in the second chicken genome sequence assembly. It was also discovered that linkage disequilibrium varied considerably between commercial layers and broilers; with the latter having haplotype blocks averaging 10 to 50 kb in size. Finally, it was estimated that commercial lines have lost 70% or more of their genetic diversity, with the majority of allele loss attributable to the limited number of chicken breeds used

Trailing and smooth-seeded wild beans: native annual warm season legumes for Texas

Last updated: 10/22/201