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Abstract Old age is associated with characteristic changes of the immune system contributing to higher incidence and severity of many infectious diseases. Particularly within the T cell compartment latent infection with human Cytomegalovirus (CMV) is contributing to and accelerating immunosenescence. However, latent CMV infection and reactivation usually does not cause overt symptoms in immunocompetent elderly persons indicating immunological control of disease. Little is still known about the clonal composition of CMV-specific T cell responses in donors of different age. We therefore analyzed CD8+ T cells specific for an immunodominant pp65-derived nonamer-peptide (NLVPMVATV; CMVNLV) in different age-groups. Independent of donor age CMVNLV-specific CD8+ T cells preferentially use the V beta family 8. This family has monoclonal expansions in the majority of donors after stimulation of CD8+ T cells with the peptide. By sequencing the CDR3 region of the T cell receptor we demonstrated that CMVNLV-specific, BV8+ CD8+ T cells share the conserved CDR3-sequence motif SANYGYT in donors of all age groups. Interestingly, a second conserved clonotype with the CDR3-sequence motif SVNEAF appears in middle-aged and elderly donors. This clonotype is absent in young individuals. The age-related clonotype SVNEAF binds to the pMHC-complex with higher avidity than the clonotype SANYGYT, which is predominant in young adults. The dominance of this high avidity clonotype may explain the lack of overt CMV-disease in old age.

X-ray crystallography and NMR spectroscopy were used to determine and probe the structure of circular permutant of Bacillus circulans xylanase. The results for the circularly permuted xylanases provides an excellent set of new start points for directed evolution of commercially important Bcx enzyme and also provides new insigth into the mechanism of enzymatic glycoside hydrolysis.

Background: Hyaluronan (HA) is present in extracellular spaces and interstitia of many tissue types. As it is capable of binding high amounts of water, HA provides ideal conditions for cell migration and proliferation. Under conditions of cellular crowding, it also permits lineage-specific differentiation and thus promotes many aspects of healing and tissue remodeling., Methods: The simplicity of its structure makes it amenable to chemical modifications and/or combined formulations with other bioactive substances. Thus a wide variety of clinical applications have been proposed, several of which are currently being implemented in advanced therapies., Results: Known features of HA biology, in particular regarding synthesis and processes related to signaling and control, have been adopted to elaborate specific products in order to support progress in regenerative medicine. Purified HA, HA-based hydrogels or special HA composites have been formulated together with other well-characterized biomaterials and bioactive factors. HA is currently employed in a variety of therapeutic applications both in its pure form and in a biofunctionalized form., Conclusions: HA plays an essential role in regenerative processes. Owing to the growing scientific knowledge in this field, medicinal products based on HA have been devised and are being routinely applied in ophthalmology or in trauma and transplantation surgery. Further areas of application are contemplated, such as the use of HA composite scaffold material in tissue engineering, or refined HA hydrogels enabling controlled release of medication., (Copyright © 2012 S. Karger AG, Basel.)

Besides SPAM1 (sperm adhesion molecule 1; formerly named PH-20), further hyaluronidase-like proteins, HYAL5 (hyaluronoglucosaminidase 5) and HYALP1 (hyaluronoglucosaminidase pseudogene 1) are also expressed in murine testicular tissue. As they share a high degree of sequence similarity with known hyaluronidases, all three polypeptides could potentially exhibit hyaluronidase activity, a function that is beneficial for spermatozoa in order to penetrate the hyaluronan-rich cumulus, which surrounds the oocyte. Recently, it was reported that SPAM1-deficient mice are fertile and spermatozoa derived from mutant mice still exhibit hyaluronidase activity [Baba, Kashiwabara, Honda, Yamagata, Wu, Ikawa, Okabe and Baba (2002) J. Biol. Chem. 277, 30310-30314]. We have now recombinantly expressed mouse SPAM1, HYAL5 and HYALP1 in Xenopus laevis oocytes and determined their respective expression pattern in testis. Transcripts of all three genes are expressed in seminiferous tubules in regions where maturing spermatogenic cells reside. SPAM1 and HYAL5 but not HYALP1 proteins exhibit hyaluronidase activity at neutral pH. The two active hyaluronidases are both bound to the cell surface via a glycosylphosphatidylinositol anchor. Furthermore, structural characteristics are discussed that are necessary for hyaluronidases in order to exhibit hyaluronan cleavage.