Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

Addressing healthy aging populations in developing countries: unlocking the opportunity of eHealth and mHealth

Aging societies worldwide propose a significant challenge to the model and organisation of the delivery of healthcare services. In developing countries, communicable and non-communicable diseases are affecting how the ageing population access healthcare; this could be due to varying reasons such as geographical barriers, limited financial support and poor literacy. New information and communication technology, such as eHealth have the potential to improve access to healthcare, information exchange and improving public and personalised medicine for elderly groups. In this article we will first frame the context of information and communication technologies in light of an aging landscape. We will also discuss the problems related to implementing the needed infrastructure for uptake of new technology, with particular emphasis on developing countries. In so doing, we highlight areas where newer technologies can serve as promising tools or vehicles to address health and healthcare-related gaps and needs of elderly people living in resource-constrained settings

Programmed assembly of nanoscale structures using peptoids.

Sequence-specific polymers are the basis of the most promising approaches to bottom-up programmed assembly of nanoscale materials. Examples include artificial peptides and nucleic acids. Another class is oligo(N-functional glycine)s, also known as peptoids, which permit greater sidegroup diversity and conformational control, and can be easier to synthesize and purify. We have developed a set of peptoids that can be used to make inorganic nanoparticles more compatible with biological sequence-specific polymers so that they can be incorporated into nucleic acid or other biologically based nanostructures. Peptoids offer degrees of modularity, versatility, and predictability that equal or exceed other sequence-specific polymers, allowing for rational design of oligomers for a specific purpose. This degree of control will be essential to the development of arbitrarily designed nanoscale structures

Biological Functions of Iduronic Acid in Chondroitin/Dermatan Sulfate.

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides, as it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties such as migration, proliferation, differentiation, angiogenesis and regulation of cytokine/growth factor activities. During pathological conditions such as wound healing, inflammation and cancer iduronic acid has diverse regulatory functions. Iduronic acid is formed by the two epimerases DS-epimerase 1 and DS-epimerase 2 which have different tissue distribution and properties. The role of IdoA in chondroitin/dermatan sulfate is underlined by the vast changes of connective tissue features in patients with a new type of Ehler-Danlos syndrome, adducted thumb-clubfoot syndrome. Future direction of research is to understand the roles of the two epimerases and their interplay with sulfotransferases involved in CS/DS biosynthesis. Further, a better definition of chondroitin/dermatan sulfate functions using different knock-out models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation and the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS

Antibodies as Natural Adjuvants

Antibodies in complex with specific antigen can dramatically change the antibody response to this antigen. Depending on antibody class and type of antigen, &gt;99 % suppression or &gt;100-fold enhancement of the response can take place. IgM and IgG3 are efficient enhancers and operate via the complement system. In contrast, IgG1, IgG2a, and IgG2b enhance antibody and CD4(+) T cell responses to protein antigens via activating Fc gamma-receptors. IgE also enhances antibody and CD4(+) T cell responses to small proteins but uses the low-affinity receptor for IgE, CD23. Most likely, IgM and IgG3 work by increasing the effective concentration of antigen on follicular dendritic cells in splenic follicles. IgG1, IgG2a, IgG2b, and IgE probably enhance antibody responses by increasing antigen presentation by dendritic cells to T helper cells. IgG antibodies of all subclasses have a dual effect, and suppress antibody responses to particulate antigens such as erythrocytes. This capacity is used in the clinic to prevent immunization of Rhesus-negative women to Rhesus-positive fetal erythrocytes acquired via transplacental hemorrage. IgG-mediated suppression in mouse models can take place in the absence of Fc gamma-receptors and complement and to date no knock-out mouse strain has been found where suppression is abrogated.</p