Damage-associated molecular patterns and their receptors in upper airway pathologies

Inflammation of the nasal (rhinitis) and sinus mucosa (sinusitis) are prevalent medical conditions of the upper airways that are concurrent in many patients; hence the terminology “rhinosinusitis”. The disease status is further defined to be “chronic” in case symptoms persist for more than 12 weeks without resolution. A diverse spectrum of external factors including viral and bacterial insults together with epithelial barrier malfunctions could be implicated in the chronicity of the inflammatory responses in chronic rhinosinusitis (CRS). However, despite massive research efforts in an attempt to unveil the pathophysiology, the exact reason for a lack of resolution still remains poorly understood. A novel set of molecules that could be implicated in sustaining the inflammatory reaction may be found within the host itself. Indeed, besides mediators of inflammation originating from outside, some endogenous intracellular and/or extracellular matrix (ECM) components from the host can be released into the extracellular space upon damage induced during the initial inflammatory reaction where they gain functions distinct from those during normal physiology. These “host-self” molecules are known to modulate inflammatory responses under pathological conditions, potentially preventing resolution and contributing to the development of chronic inflammation. These molecules are collectively classified as damage-associated molecular patterns (DAMPs). This review summarizes the current knowledge regarding DAMPs in upper airway pathologies, also covering those that were previously investigated for their intracellular and/or ECM functions often acting as an antimicrobial agent or implicated in tissue/cell homeostasis, and for which their function as a danger signaling molecule was not assessed. It is, however, of importance to assess these molecules again from a point of view as a DAMP in order to further unravel the pathogenesis of CRS.     

Modelling T-cell memory by genetic marking of memory T cells in vivo.

Immunological memory is the ability of the immune system to respond with enhanced vigour to pathogens that have been encountered in the past. Following infection or immunization, most effector T cells undergo apoptotic cell death, but a small fraction of these cells, proportional to the early antigen load and initial clonal burst size, persist in the host as a stable pool of memory T cells. The existence of immunological memory has been recognized for over 2,000 years, but our understanding of this phenomenon is limited, primarily because memory lymphocytes cannot be unequivocally identified as they lack specific, permanent markers. Here we have developed a transgenic mouse model system whereby memory T cells and their precursors can be irreversibly marked with a reporter gene and thus can be unambiguously identified. Adoptive transfer of marked CD8+ T cells specific for lymphocytic choriomeningitis virus protected naive recipients following viral challenge, demonstrating that we have marked memory T cells. We also show that cytotoxic effector lymphocytes that develop into memory T cells can be identified in the primary response.     

The M-superfamily of conotoxins: a review

The focus of this review is the M-superfamily of Conus venom peptides. Disulfide rich peptides belonging to the M-superfamily have three loop regions and the cysteine arrangement: CC–C–C–CC, where the dashes represent loops one, two, and three, respectively. Characterization of M-superfamily peptides has demonstrated that diversity in cystine connectivity occurs between different branches of peptides even though the cysteine pattern remains consistent. This superfamily is subdivided into five branches, M-1 through M-5, based on the number of residues in the third loop region, between the fourth and fifth cysteine residues. M-superfamily peptides appear to be ubiquitous in Conus venom. They are largely unexplained in indigenous biological function, and they represent an active area of research within the scientific community.     

Effects of hexamethylenebisacetamide on the differentiation of embryonal carcinoma cells]

HMBA induces differentiation in the whole population of some multipotential embryonic carcinoma cells. Morphological, biochemical and immunological changes can be observed even after short treatment. The cells lose the embryonal F9 antigen without acquiring H-2 antigens.     

Evolution of the Archaean crust by delamination and shallow subduction

The Archaean oceanic crust was probably thicker than present-day oceanic crust owing to higher heat flow and thus higher degrees of melting at mid-ocean ridges. These conditions would also have led to a different bulk composition of oceanic crust in the early Archaean, that would probably have consisted of magnesium-rich picrite (with variably differentiated portions made up of basalt, gabbro, ultramafic cumulates and picrite). It is unclear whether these differences would have influenced crustal subduction and recycling processes, as experiments that have investigated the metamorphic reactions that take place during subduction have to date considered only modern mid-ocean-ridge basalts. Here we present data from high-pressure experiments that show that metamorphism of ultramafic cumulates and picrites produces pyroxenites, which we infer would have delaminated and melted to produce basaltic rocks, rather than continental crust as has previously been thought. Instead, the formation of continental crust requires subduction and melting of garnet-amphibolite--formed only in the upper regions of oceanic crust--which is thought to have first occurred on a large scale during subduction in the late Archaean. We deduce from this that shallow subduction and recycling of oceanic crust took place in the early Archaean, and that this would have resulted in strong depletion of only a thin layer of the uppermost mantle.The misfit between geochemical depletion models and geophysical models for mantle convection (which include deep subduction) might therefore be explained by continuous deepening of this depleted layer through geological time.